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Background: Congenital Pseudarthrosis of the Tibia (CPT) is a rare pediatric condition presenting substantial challenges for orthopedic surgeons. Aiming to achieve bone union, with subsequent complications such as refractures being common. The aim of the present study is to evaluate the results of our intentional cross-union protocol and to compare these outcomes with those obtained from our previously used techniques., Materials and Methods: Sixteen patients, with a mean age of 4.8 years (range: 1-13.3 years), who were treated with the intentional cross-union protocol were included in Group (A) Eleven patients, with a mean age of 3.5 years (range: 1.3-7.6 years), who primarily underwent intramedullary rodding with bone graft, were included in Group (B) The intentional cross-union protocol involved cross-union of the tibia and fibula, autogenous iliac bone grafting, and the insertion of bone morphogenetic protein 2 (BMP-2) aimed at achieving tibia-fibula cross-union. Retrospective evaluation of serial radiographs was conducted, and the outcomes regarding union and any subsequent complications were analyzed., Results: A total of 27 patients with CPT were included in the study. All 16 patients (100%) in Group A successfully achieved primary union. Among the 11 patients in Group B, only 4 cases achieved primary union, with a primary healing rate of 36.4%. Seven cases with delayed healing required 2-4 revision surgeries for final healing. The time to union was significantly shorter in Group A (3.37 ± 0.64 months) compared to Group B (8.67 ± 3.0 months). The cross-sectional area of union was also significantly larger in Group A (6.71 ± 0.58 cm²) compared to Group B (1.18 ± 0.19 cm²). In Group A, there were no cases of refracture, whereas in Group B, 7 cases (77.8%) experienced refracture, indicating a statistically significant difference., Conclusions: Our study demonstrates that the Cross-union protocol is highly effective for achieving union and preventing refracture in CPT. With such significant improvement, it has notably altered the prognosis of this challenging condition., Level of Evidence: IV., Competing Interests: Declarations. Ethics approval and consent to participate: Our study was approved by The Ethics Committee approval of Children’s hospital of Fudan university and conducted according to the Helsinki Declaration and its later amendments. Consent for publication: All participants were informed about the purpose of the study and informed consent was obtained for all patient images from a parent and/or legal guardian. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To evaluate if regenerative materials with/without scaffold deployed in dental socket preservation led to reduced radiographic height and width bone resorption., Study Design: English-written human studies from January 2010 to December 2023 were selected from PubMed, EMBASE, MEDLINE, Cochrane CENTRAL, Google Scholar and manually searched journals. Six meta-analyses were conducted, addressing treatments with all blood-derived growth factor preparations as well as L-platelet-rich fibrin (L-PRF) separately, and recombinant human BMP-2 (rhBMP-2). An unpaired t-test on L-PRF and rhBMP-2 determined the clinically best preservation treatment. Cochrane risk of bias in all studies was analyzed., Results: Twenty-nine articles (1068 participants) were included. Meta-analyses on blood-derived preparations demonstrated nonsignificant alveolar width, but significant (p = .001) height preservation. L-PRF vs. natural healing demonstrated nonsignificant changes in both dimensions. RhBMP-2 caused highly significant reduced horizontal (p = .01) and vertical (p < .0008) bone resorptions. When comparing mean resorption rates, significant benefits of rhBMP-2 over L-PRF were observed for width but not height preservation (p < .0001 and p = .057, respectively). Six studies recorded low, 8 moderate, and 15 high net risks., Conclusions: Regenerative materials appear beneficial for radiographic bone width and height preservation after tooth extraction. Although rhBMP-2 performed better in alveolar width preservation, L-PRF can be an autologous and cost-effective alternative., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To investigate the application of recombinant human bone morphogenetic protein-2 (RhBMP-2) in Percutaneous Endoscopic Posterior Lumbar Interbody Fusion (PE-PLIF)., Materials and Methods: The study randomly included 102 patients with lumbar spondylosis who underwent PE-PLIF at our hospital from April 2020 to August 2022. Following the random number table method, these subjects were graded as a study group of 51 cases and a control group of 51 cases. Posterior pedicle screw fixation treatment with RhBMP-2 or autologous bone was given respectively. The surgical status and perioperative complications, as well as lumbar spine function before surgery and at 1 and 12 months after surgery [Prolo score and Japanese Orthopaedic Association (JOA) score] of patients in the two groups were observed, and the postoperative fusion rate and cage displacement rate at 1 and 12 months after surgery were compared between the two groups. The degree of vertebral body slippage, intervertebral space height, and changes in quality of life were compared between the two groups before and 12 months after surgery., Results: There was no significant difference in hospital stay, surgical time, bleeding volume, and incidence of complications between the two groups (P > 0.05)0.12 months post-operation, the Prolo and JOA scores of both groups largely increased, which were significantly higher in the RhBMP-2 group than the control (P < 0.05). 12 months post-operation, the fusion rate in the RhBMP-2 group was 86.27%, which was significantly higher than that of 54.90% in the control group (P < 0.05). 12 months post-operation, the Cage displacement rate in the RhBMP-2 group was 5.88%, which was lower than that of 21.57% in the control group (P < 0.05). 12 months post-operation, the height of the intervertebral space in both groups largely increased, which was significantly higher in the RhBMP-2 group than in the control (P < 0.05). The degree of vertebral body slippage was significantly reduced in both groups, and the RhBMP-2 group was significantly lower than the control (P < 0.05). The cognitive function, social function, physiological function, and mental health were evidently improved in both groups 12 months post-operation and were significantly higher in the RhBMP-2 group than in the control (P < 0.05)., Conclusion: RhBMP-2 material in PE-PLIF could significantly restore lumbar function, promote postoperative fusion, reduce Cage displacement and vertebral slippage, accelerate recovery of lumbar intervertebral space, and improve patient quality of life., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All procedures performed in studies involving humans were in accordance with the ethical standards of the ethics committee of the Ganzhou People’s Hospital (approval number: 2023-09-07). Consent for publication: Informed consent was obtained from all individual participants included in the study. The patients participating in the study all agree to publish the research results. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Case Presentation: Although most peri-implant lesions feature a combined defect configuration that involves both supra- and infraosseous components, regenerating the supraosseous part is considered the optimal approach, albeit a challenging one, and often requires vertical bone augmentation. This report provides a detailed description of submerged membrane techniques for vertical bone augmentation around supraosseous peri-implant defects. Cases involving different types of membrane (both resorbable and non-resorbable) with or without the use of bone graft are presented. In the first case, the patient had a mild supraosseous defect that was managed using the sausage technique with collagen matrix soaked with human recombinant bone morphogenetic protein-2. In cases two to five, titanium-reinforced dense polytetrafluoroethylene membranes were employed., Conclusion: The reconstruction of supraosseous peri-implant defects is technique sensitive but can be achieved when adhering to the principles of space maintenance and submerged healing.

BACKGROUND  : The use of bone morphogenic protein (BMP-2) in adult spine deformity (ASD) surgery remains controversial more than two decades following its approval for clinical application in spine surgery. This study was performed to assess outcomes in patients undergoing ASD surgery with BMP application compared with a combination of bone marrow aspirate, cancellous bone chips and i-Factor., Methods: This was a retrospective cohort study. ASD patients were stratified by use of intra-operative BMP (BMP +) or not (BMA + I) and surveyed for the development of complications and mechanical failure. Quality of life gained following the procedure was evaluated using quality-adjusted life years (QALYs). Cost was calculated using the PearlDiver database and CMS definitions. Multivariable analyses (ANCOVA) and logistic regression were used to adjust for confounding., Results: 512 patients were included (60% BMP +). At baseline, BMP + patients were older (62.5 vs 60.8 years, p < 0.010). Radiographic and quality-of-life metrics did not differ at follow up timepoints (all p > 0.05). BMP use was associated with higher supplemental rod use (OR: 7.0, 1.9 - 26.2, p = 0.004), greater number of levels fused (OR: 1.1, 1.03 - 1.17, p = 0.003) and greater neurological complications (OR: 5.0, 1.3 - 18.7, p = 0.017). Controlling for rod use and levels fused, BMP use was not associated with a lower risk of mechanical complications (OR 0.3, 95% CI: 0.2 - 3.0, p = 0.353), rod breakage (OR: 3.3, 0.6 - 18.7, p = 0.182) or implant failure (OR: 0.3, 0.04 - 1.51). At 2 years, the BMP + cohort exhibited higher overall costs ($108,062 vs $95,144, p = 0.002), comparable QALYs (0.163 vs 0.171, p = 0.65) and higher cost per QALY (p = 0.001) at two years., Conclusions: In this analysis, BMP-2 application was not associated with superior outcomes when compared to a less costly biologic alternative (bone marrow aspirate + cancellous bone chips + i-Factor) following ASD surgery. The use of BMP-2 in ASD surgery appears to have reduced cost-efficacy at two years postoperatively., Competing Interests: Declarations Ethical approval This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of NYU School of Medicine. Informed consent Informed consent was obtained from each patient prior to enrollment. Competing interests Peter G. Passias Cerapedics: Other financial or material support Cervical Scoliosis Research Society: Research support Globus Medical: Paid presenter or speaker Medtronic: Paid consultant Royal Biologics: Paid consultant Spine: Editorial or governing board Spinevision: Other financial or material support SpineWave: Paid consultant JNS Spine: Editorial Board JCM: Editorial Board., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Patients within the US Veterans Health Administration (VA) system have higher rates of comorbidities and chronic pain, increasing risks of complications/poor outcomes following spine surgery. Although the use of bone morphogenetic protein 2 (BMP-2) is established for anterior lumbar interbody fusion, its indications for off-label use in posterolateral fusion are unclear. The objective of this study was to evaluate safety and utility of BMP-2 in posterolateral fusion through a 15-year experience at the VA., Methods: Patients underwent posterolateral lumbosacral fusions with BMP-2 by a single VA surgeon from January 1, 2005, to January 1, 2020. The primary outcome was fusion assessed through postoperative radiographs. Secondary outcomes included adjacent segment disease (ASD) and postoperative pain clinic utilization., Results: Sixty-eight patients underwent lumbosacral posterolateral fusion with BMP-2; 77.9% were discharged home and had no postoperative complications. All patients achieved bony fusion at a mean of 113.3 ± 59.9 days postoperatively. Five patients were diagnosed with cancer postoperatively, and eight patients required revision for ASD. No notable predictors of ASD exist. Preoperative opioid use predicted postoperative pain clinic utilization., Discussion: Posterolateral lumbar fusion with BMP-2 in veterans yields high fusion rates and favorable complication profiles and should be considered in multimorbid hosts., Study Design: Retrospective review of prospectively collected data., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Introduction: Recent studies have shown a growing concern regarding the cost-effectiveness and the lack of supporting data for the biologic agents that are being increasingly used in the orthopedic field. Our aim was to conduct a systematic scoping review of recent publications (last five years) on the use of orthobiologics to treat fracture non-union and summarize the latest available data., Patients and Methods: The inclusion criteria for this review were articles published in English, from 2016 to 2022, and focusing on the use of orthobiologics for the surgical treatment of non-union. Searches were conducted in March 2023 using Pubmed/MEDLINE and Embase. Studies on spinal fusion or gene therapy were excluded. Reviews, case reports with five cases or less, conference proceedings, preliminary reports, pediatric or non-human studies were excluded as well., Results: The search found 1807 articles, 15 were eligible after PRISMA checklist and exclusions. The evidence was heterogenous and there was only one level II RCT. Recent data suggests that bone morphogenic protein (BMP-2) products could be effective for septic and aseptic tibial non-unions. However, the evidence was not conclusive regarding BMP-7, plasma rich platelets (PRP), stem cells or demineralized bone matrix (DBM)., Discussion: Every non-union case is different in terms of bone defect, biology, mechanical stability, surgical technique and host factors, which contributes to the conflicting reports on the efficacy of orthobiologics in the literature. We might never see a level 1, high powered and robust study defining the efficacy, safety profile and cost-effectiveness of such products., Level of Evidence: IV., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Introduction: Recombinant human Bone morphogenetic proteins have been used for the treatment of nonunions with promising results. We have been investigating both experimentally and clinically the efficacy of the rhBMP-2 with the macro / micro-porous hydroxyapatite carrier granules on the potency on the reconstruction of long bone defect. The purpose of this study was to prospectively evaluate the efficacy and safety of this specific rhBMP-2 with HA carrier granules mixed with autologous cancellous bone in patients with nonunion and bone defect resulted from the fracture related infection., Materials and Methods: This was a retrospective review of a prospective cohort at a university hospital. Patients diagnosed with nonunion under the definition of the United States Food and Drug Administration with bone defect after long bone fractures were enrolled from January 2020 to February 2021. We included patients with atrophic and oligotrophic nonunion, and hypertrophic nonunion with malalignment that needed to be corrected. The other patient group was consisted of segmental bone defect resulted from FRI. The maximum amount of rhBMP-2 allowed in this clinical study was 6 mg and was added to autologous bone at a 1:1 ratio. Autologous bone was added to the mixture if the volume of mixed graft was insufficient to fill the bone defect. Patients were followed 3, 6, and 12 months post-operatively. Each visit, a radiograph was taken for assessment. Visual analog scale (VAS), questionnaire for quality of life (SF-12 physical component summary [PCS], mental component summary [MCS]), and weight-bearing status were collected for functional outcome assessment. Drug safety was assessed by examining BMP-2 antibodies., Results: Of the 24 enrolled patients (mean age: 57 years), 15 (62.5 %), 2 (8.33 %), and 7 (29.17 %) presented atrophic nonunion, hypertrophic nonunion with deformity, and bone defect after fracture related infection, respectively. Thirteen patients had nonunion in the femur, 9 in the tibia, and 1 in the humerus and radius. The average amount of harvested autologous bone was 9.25 g and 4.96 mg of rhBMP-2. All 24 patients achieved union after 1-year follow up. The union rate was 95.83 % and 100 % at 6 and 12 months postoperatively, respectively. Preoperative SF-12 PCS (mean: 34.71) improved at 6 and 12 months postoperatively, respectively. Preoperative SF-12 MCS (mean: 42.89) improved 12 months postoperatively (49.13, p = 0.0338). Change of VAS was statistically significant 3 months postoperatively (p = 0.0012). No adverse effects or development of BMP-2 antibodies were observed., Conclusion: BMP-2 combined with autogenous bone resulted in excellent radiographical and functional outcomes in a relatively small prospective series of patients with nonunion and bone defect, without adverse effects. Further investigations are necessary to support our finding and optimize treatment strategies in nonunion patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: The surgical management of severe scoliosis in patients with osteogenesis imperfecta (OI) is challenging because of curve rigidity, small stature, and inherent bone fragility. This study evaluated the midterm outcomes of our multimodal approach to address these issues, integrating perioperative bisphosphonate therapy, preoperative/intraoperative traction, various osteotomies, segmental pedicle screw instrumentation with cement augmentation, and bone morphogenetic protein-2 application., Methods: A single-center retrospective review of 30 patients (average age 14.1 ± 2.2 years; 18 were female) diagnosed with OI and scoliosis was conducted. These patients underwent posterior spinal fusion between 2008 and 2020 and completed a minimum follow-up of 2 years. We measured radiographic parameters at each visit and reviewed the incidence of complications. A mixed-effects model was used to evaluate changes in radiographic parameters from preoperative measurements to the first and latest follow-ups., Results: The patient cohort consisted of 2 individuals with type I OI, 20 with type III, 6 with type IV, and 2 with other types (types V and VIII). Surgical intervention led to a notable improvement in the major curve magnitude from 76° to 36°, with no notable correction loss. In addition, the minor curve, apical vertical translation, lowest instrumented vertebra tilt, and pelvic obliquity were also improved. In the sagittal plane, thoracic kyphosis and lumbar lordosis remained unchanged while thoracolumbar kyphosis markedly improved. Two patients experienced proximal junctional kyphosis with screw pullout, one of whom required revision surgery. One patient developed a superficial infection that was successfully treated with oral antibiotics. No instances of neurologic deficits or cement extravasation were observed., Discussion: This study demonstrated the effectiveness and safety of our multimodal approach to treating scoliosis in patients with OI, achieving a 53% major curve correction with minimal complications over 2-year follow-up. These findings provide notable insights into managing scoliosis in this population., Level of Evidence: Level IV (case series)., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

The secondary alveolar bone grafting procedure is typically recommended during the late mixed dentition phase, prior to the eruption of the permanent canine, in patients with cleft lip and palate. The anatomical and functional adaptations observed in the grafted area allow spontaneous migration and eruption of the adjacent maxillary canine. An alveolar bone graft can be performed using autogenous bone or recombinant human bone morphogenetic protein-2 (rhBMP-2). Employing rhBMP-2 in a collagen membrane eliminates the need for a donor site, thus reducing surgical morbidity. This paper aims to present a case involving complete orthodontic rehabilitation with a three-year follow-up of a male patient with a unilateral complete cleft lip and palate, posterior and anterior crossbite, where grafting was performed with rhBMP-2 at a single centre. Orthodontic intervention began at 8 years of age with rapid maxillary expansion, followed by facemask therapy. The alveolar bone grafting procedure was performed using rhBMP-2 in a collagen membrane, according to the surgical protocol developed by the Oslo team. Comprehensive orthodontic treatment started 15 months post bone grafting, during which the maxillary permanent lateral incisor distal to the alveolar cleft was successfully moved mesially into the grafted region. This intervention resulted in adequate occlusal and periodontal outcomes. The alveolar graft with rhBMP-2 produced adequate and stable alveolar bone formation, facilitating tooth eruption, orthodontic movement, and stability at the cleft site., (Copyright © 2024 CEO. All rights reserved.)

The aim of this retrospective study was to assess the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with hydroxyapatite (HA) granules and fibrin sealant (FS) in maxillary sinus floor augmentation (MSFA), with a focus on the volume change. Fifty-two of 137 patients who underwent MSFA with rhBMP-2/HA grafting between June 2016 and December 2022 met the study inclusion criteria; 25 had received rhBMP-2/HA without FS and 27 had received rhBMP-2/HA with FS. Computed tomography (CT) images were obtained preoperatively, immediately following the operation, and at 6 months postoperative. These images were three-dimensionally reconstructed to measure the volumetric and height changes following MSFA. The mean ± standard deviation percentage of volumetric change at 6 months was 48.75 ± 37.44% in the group with FS and 29.77 ± 13.42% in the group without FS (P = 0.019). The vertical height measured at a specific site of the grafted area showed a mean percentage change at 6 months of 4.05 ± 12.08% in the group with FS and 6.07 ± 10.15% in the group without FS (P = 0.518). The additional use of FS as a carrier for rhBMP-2/HA in MSFA was found to improve surgical convenience and bone regeneration ability., (Copyright © 2024 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the influence of filling material and timing of surgery on radiograph outcomes of alveolar grafting with premaxillary osteotomy. The null hypothesis was that radiographic outcomes would be similar with both rhBMP-2 (rhBMP-2G) and cancellous bone from the iliac crest (IG), regardless of the timing of surgery., Design: Cross-sectional study with consecutive sampling of 56 periapical or occlusal radiographs taken 12 months after surgery., Setting: A single tertiary craniofacial center., Patients/participants: Twenty-eight patients with complete bilateral cleft lip and palate and mean age of 13 years. The individuals underwent bilateral alveolar grafting associated with premaxillary osteotomy (AG + PO) with rhBMP-2 or cancellous bone from the iliac crest., Interventions: Experienced maxillofacial surgeons used the same surgical technique in both groups. AG + PO were assigned as success or failure by 3 blinded raters based on modified Bergland and SWAG scales., Main Outcome Measures: The influence of filling materials and timing of surgery on radiographic outcomes was verified by Fisher's exact test and chi-square test ( P  < .05)., Results: There was no significance variation between the mean age of participants in the rhBMP-2G and IG ( P  = .471). Scales showed almost perfect reliability (agreement rate = 96.4%; K = 0.85). rhBMP-2G and IG had similar success rates with modified Bergland scale (85.7% and 82.1%) and SWAG scale (92.9% and 82.1%), respectively. However, only modified Bergland scale found influence of age on radiographic outcomes ( P  = .025)., Conclusions: AG + PO performed with rhBMP-2 and iliac crest bone showed similar radiographic success rates, regardless of the timing of surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study investigates the effectiveness of demineralized bone matrix (DBX) to close alveolar clefts in patients previously treated with bone morphogenic protein-2 (BMP-2) who remained with bone nonunion., Design: This is an IRB-approved retrospective, single-center study., Setting: This study was conducted at a tertiary academic center., Patients/participants: We searched for all surgical encounters with the Current Procedural Terminology (CPT) code 42210 from the years 2013-2019. Included patients were diagnosed with cleft alveolus, previous BMP-2 exposure and required revision bone grafting during mixed dentition for persistent alveolar defects., Interventions: 17 patients underwent revision alveolar bone grafting (ABG) with either DBX (n = 10) or autograft (n = 7) to repair persistent bony cleft., Main Outcome Measure(s): The primary study outcome measured was alveolar bone graft revision failure described as continued alveolar nonunion., Results: The median age at revision ABG was 13.1 ± 3.3 years, with a mean follow-up time of 4.9 years (1.1-9.2 years). Patients were 53% male, 47% had a unilateral cleft lip and alveolus. 58.8% of patients were treated with DBX in the cleft, 41.2% treated with autograft from iliac crest. Overall, 11.8% (n = 2) of all revisions failed, requiring a second revision. The average time to reoperation was 2.06 years, and both were re-grafted with autograft. There was no statistically significant difference between the type of bone graft source used and the failure rate obtained ( P  = .1544)., Conclusions: DBX and autologous iliac crest bone grafts achieve similar alveolar union rates during revision ABG in patients treated with previous BMP-2 to the alveolar cleft., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To report the operative outcomes after treating vertebral osteomyelitis patients with an anterior cervical corpectomy and fusion procedure using recombinant human bone morphogenetic protein-2 (rhBMP-2) as graft material., Methods: A retrospective review of electronic medical records of 26 adult patients who underwent an anterior cervical corpectomy and fusion procedure for cervical osteomyelitis using rhBMP-2 at the University of Puerto Rico University District Hospital was performed. Indication, preoperative laboratory results, levels of corpectomy, preoperative American Spinal Injury Association Impairment Scale (ASIA) score, complications, fusion evaluation at 12 months, and ASIA score at 12 months were reviewed., Results: For the cohort of patients, mean age was 47 ± 13 years and 65% were male. Spinal instability was present in 54%. The levels of corpectomy were: 1 level in 2 cases, 2 levels in 15 cases, 3 levels in 8 cases, and 5 levels in 1 case. Four patients had complications and, of these, 2 experienced dysphagia. The fusion rate was 100% and no reoperations were performed. An improvement in ASIA score was seen for 54% patients at 12-month follow-up., Conclusions: This study demonstrates a fusion rate of 100% with no reoperations reported. Recombinant human bone morphogenetic protein-2 could be considered and further researched as grafting material for anterior cervical corpectomy and fusion procedures in cervical osteomyelitis patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The objective was to describe the indications, technique, and initial outcomes of autologous rib graft with recombinant human bone morphogenetic protein (rhBMP) in pediatric patients undergoing posterior cervical fusion., Methods: A retrospective study was performed of all pediatric patients who underwent autologous rib grafting with extra-small rhBMP-2 for posterior craniocervical or cervical arthrodesis at a single institution between May 2020 and July 2023. Patients with less than 3 months of postoperative follow-up and no postoperative CT data were excluded. Primary outcomes included presence of fusion on CT, 30-day perioperative complications, and rib harvest complications., Results: Twenty-eight sequential patients met inclusion criteria. Thirteen were male, 15 were female, and the average age was 9 years. There were no surgical site infections or instances of postoperative seroma or unplanned return to the operating room. All patients had solid fusion on postoperative CT at 3 months. The average follow-up was 14.5 months, with a range of 4 months to 3 years. There were no complications associated with the rib harvest, including no instances of harvest site pain, and all patient incisions healed well., Conclusions: The authors' preliminary results demonstrate that autologous rib graft with extra-small rhBMP-2 is an effective strategy to achieve a high rate of fusion in pediatric patients undergoing posterior instrumented craniocervical or cervical fusion. In this series, the authors found an acceptable safety profile, without seroma, surgical site infection, unplanned return to the operating room, or rib harvest complications.

Objective: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been demonstrated to achieve the highest rates of arthrodesis in multilevel lumbar fusion but is also associated with possible perioperative morbidity. A novel allograft (OSTEOAMP) is a differentiated allograft that retains growth factors supporting bone healing. The authors sought to compare the clinical and radiographic outcomes of rhBMP-2 and the novel allograft in lumbar interbody arthrodesis to determine if the latter may be a safer and equally effective alternative to rhBMP-2 for single- and multilevel posterior or transforaminal lumbar interbody fusion (PLIF or TLIF)., Methods: Patients who underwent single- or multilevel TLIF or PLIF using either OSTEOAMP or rhBMP-2 at the authors' institution over a 2-year period were prospectively followed for 12 months. Healthcare utilization, safety measures, patient satisfaction, physical disability (measured on the Oswestry Disability Index [ODI]), back and leg pain (on the numeric rating scale [NRS]), quality of life (on the EQ-5D scale), and return to work (RTW) were prospectively recorded. For purposes of this study, this consecutive series was retrospectively analyzed and pseudarthrosis rates were assessed at 2 years of follow-up. All patients (100%) had both 12-month patient-reported outcome follow-up and 24-month clinical and radiographic follow-up., Results: One thousand one hundred fifty-four patients (654 treated with OSTEOAMP, 500 with rhBMP-2) were prospectively enrolled in the institutional registry. After propensity score matching, there were no significant baseline differences between 330 novel allograft and 330 rhBMP-2 cases. Perioperative morbidity and 90-day hospital readmission (3.3% vs 2.4%, p = 0.485) did not significantly differ between the novel allograft and the rhBMP-2 cases. At the 2-year follow-up, symptomatic pseudarthrosis requiring revision surgery occurred in 8 patients (2.4%) with OSTEOAMP and 6 patients (1.8%) with rhBMP-2 (p = 0.589). The overall fusion rate at 2 years was similar between groups (p = 0.213). Both groups showed significant and equivalent improvement in patient-reported outcome measures (PROMs) from baseline to 12-month follow-up, with no significant difference in 1-year mean NRS leg pain score (2.5 vs 2.7), ODI (25 vs 26), quality-adjusted life years (0.73 vs 0.73), satisfaction (83% vs 80%), or RTW (6.6 vs 7 weeks)., Conclusions: In the authors' institutional experience, OSTEOAMP is a clinically viable substitute for rhBMP-2 for single- and multilevel lumbar fusion. This novel allograft provides clinically effective arthrodesis and improvements in PROMs comparable to rhBMP-2 with a similar safety profile. Additional indications and outcome assessment in longitudinal studies are needed to further characterize this allogeneic graft.

Osteoporosis poses a major public health challenge, and it is characterized by low bone mass, deterioration of the microarchitecture of bone tissue, causing a consequent increase in bone fragility and susceptibility to fractures and complicating bone fixation, particularly screw implantation. In the present study, our aim was to improve implant stability in osteoporotic bone using a thermoresponsive hyaluronan hydrogel (HA-pNIPAM) to locally deliver the bisphosphonate zoledronic acid (ZOL) to prevent bone resorption and bone morphogenetic protein 2 (BMP2) to induce bone formation. Adult female Wistar rats (n = 36) were divided into 2 treatment groups: one group of SHAM-operated animals and another group that received an ovariectomy (OVX) to induce an osteoporotic state. All animals received a polyetheretherketone (PEEK) screw in the proximal tibia. In addition, subgroups of SHAM or OVX animals received either the HA-pNIPAM hydrogel without or with ZOL/BMP2, placed into the defect site prior to screw implantation. Periprosthetic bone and implant fixation were monitored using longitudinal in vivo microCT scanning post-operatively and at 3, 6, 9, 14, 20 and 28 days. Histological assessment was performed post-mortem. Our data showed that pure hydrogel has no impact of implant fixation The ZOL/BMP2-hydrogel significantly increased bone-implant contact and peri-implant bone fraction, primarily through reduced resorption. STATEMENT OF CLINICAL SIGNIFICANCE: Local delivery of ZOL and BMP2 using a biocompatible hydrogel improved implant stability in osteoporotic bone. This approach could constitute a potent alternative to systemic drug administration and may be useful in avoiding implant loosening in clinical settings., Competing Interests: Declaration of competing interest The authors are not compensated, and no other institutional subsidies, corporate affiliations, or funding sources support this work unless clearly documented and disclosed. No external funds were received in support of this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Contemporary oral tissue engineering strategies involve recombinant human growth factor approaches to stimulate diverse cellular processes including cell differentiation, migration, recruitment, and proliferation at grafted areas. Recombinant human growth factor applications in oral hard and soft tissue regeneration have been progressively researched over the last 25 years. Growth factor-mediated surgical approaches aim to accelerate healing, tissue reconstruction, and patient recovery. Thus, regenerative approaches involving growth factors such as recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human bone morphogenetic proteins (rhBMPs) have shown certain advantages over invasive traditional surgical approaches in severe hard and soft tissue defects. Several clinical studies assessed the outcomes of rhBMP-2 in diverse clinical applications for implant site development and bone augmentation. Current evidence regarding the clinical benefits of rhBMP-2 compared to conventional therapies is inconclusive. Nevertheless, it seems that rhBMP-2 can promote faster wound healing processes and enhance de novo bone formation, which may be particularly favorable in patients with compromised bone healing capacity or limited donor sites. rhPDGF-BB has been extensively applied for periodontal regenerative procedures and for the treatment of gingival recessions, showing consistent and positive outcomes. Nevertheless, current evidence regarding its benefits at implant and edentulous sites is limited. The present review explores and depicts the current applications, outcomes, and evidence-based clinical recommendations of rhPDGF-BB and rhBMPs for oral tissue regeneration., (© 2023 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.)

The study aimed to analyze bone regeneration in critical-size defects using hybrid scaffolds biomechanically adapted to the specific defect and adding the growth factor rhBMP-2. For this animal study, ten minipigs underwent bilateral defects in the corpus mandibulae and were subsequently treated with novel cylindrical hybrid scaffolds. These scaffolds were designed digitally to suit the biomechanical requirements of the mandibular defect, utilizing finite element analysis. The scaffolds comprised zirconium dioxide-tricalcium phosphate (ZrO 2 -TCP) support struts and TCP foam ceramics. One scaffold in each animal was loaded with rhBMP-2 (100 μg/cm³), while the other served as an unloaded negative control. Fluorescent dyes were administered every 2 weeks, and computed tomography (CT) scans were conducted every 4 weeks. Euthanasia was performed after 3 months, and samples were collected for examination using micro-CT and histological evaluation of both hard and soft tissue. Intravital CT examinations revealed minor changes in radiographic density from 4 to 12 weeks postoperatively. In the group treated with rhBMP-2, radiographic density shifted from 2513 ± 128 (mean ± SD) to 2606 ± 115 Hounsfield units (HU), while the group without rhBMP-2 showed a change from 2430 ± 131 to 2601 ± 67 HU. Prior to implantation, the radiological density of samples measured 1508 ± 30 mg HA/cm³, whereas post-mortem densities were 1346 ± 71 mg HA/cm³ in the rhBMP-2 group and 1282 ± 91 mg HA/cm³ in the control group (p = 0.045), as indicated by micro-CT measurements. The histological assessment demonstrated successful ossification in all specimens. The newly formed bone area proportion was significantly greater in the rhBMP-2 group (48 ± 10%) compared with the control group without rhBMP-2 (42 ± 9%, p = 0.03). The mean area proportion of remaining TCP foam was 23 ± 8% with rhBMP-2 and 24 ± 10% without rhBMP-2. Successful bone regeneration was accomplished by implanting hybrid scaffolds into critical-size mandibular defects. Loading these scaffolds with rhBMP-2 led to enhanced bone regeneration and a uniform distribution of new bone formation within the hybrid scaffolds. Further studies are required to determine the adaptability of hybrid scaffolds for larger and potentially segmental defects in the maxillofacial region., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Summary: The management of bone defects and nonunions creates unique clinical challenges. Current treatment alternatives are often insufficient and frequently require multiple surgeries. One promising option is bone morphogenetic protein-2 (BMP-2), which is the most potent inducer of osteogenesis. However, its use is associated with many side effects, related to the delivery and high doses necessary. To address this need, we developed an ex vivo biomimetic hematoma (BH), replicating naturally healing fracture hematoma, using whole blood and the natural coagulants calcium and thrombin. It is an autologous carrier able to deliver reduced doses of rhBMP-2 to enhance bone healing for complex fractures. More than 50 challenging cases involving recalcitrant nonunions and bone defects have already been treated using the BH delivering reduced doses of rhBMP-2, to evaluate both the safety and efficacy. Preliminary data suggest the BH is currently the only clinically used carrier able to effectively deliver reduced doses (∼70% less) of rhBMP-2 with high efficiency, rapidly and robustly initiating the bone repair cascade to successfully reconstruct complex bone injuries without side effects. The presented case provides a clear demonstration of this technology's ability to significantly alter the clinical outcome in extremely challenging scenarios where other treatment options have failed or are considered unsuitable. A favorable safety profile would portend considerable promise for BH as an alternative to bone grafts and substitutes. Although further studies regarding its clinical efficacy are still warranted, this novel approach nevertheless has tremendous potential as a favorable treatment option for bone defects, open fractures, and recalcitrant nonunions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This study defined and compared the course of native, impaired and growth factor-stimulated bone regeneration in a rat femoral defect model. A mid-diaphyseal defect with rigid internal fixation was surgically created in the right femur of male Fischer rats and serially analyzed over 36 weeks. Native bone regeneration was modeled using a sub-critical, 1 mm size defect, which healed uneventfully. Critical size defects of 5 mm were used to analyze impaired bone regeneration. In a third group, the 5 mm defects were filled with 11 µg of recombinant human bone morphogenetic protein 2 (rhBMP2) impregnated onto an absorbable collagen sponge, modeling its clinical use. Native bone regeneration was characterized by endochondral ossification with progressive remodeling to ultimately resemble intact femora. An endochondral response was also observed under conditions of impaired bone regeneration, but by week 8 medullary capping occurred with fibrofatty consolidation of the tissue within the defect, resembling an atrophic non-union. rhBMP2 treatment was associated with prolonged inflammatory cytokine expression and rapid intramembranous bone formation occurring with reduced expression of cartilage-associated collagens. Between weeks 4 and 36, rhBMP2-treated bones demonstrated decreased trabecular number and increased trabecular separation, which resulted in inferior mechanical properties compared with bones that healed naturally. Clinical Significance: Recombinant human bone morphogenetic protein 2 (rhBMP2) is used clinically to promote healing of long bones. Our data suggest that it drives intramembraneous ossification producing an inferior regenerate that deteriorates with time. Clinical outcomes would be improved by technologies favoring endochondral regenerative ossification., (© 2023 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Purpose: To study the effect of BMP-2 on the volumetric and histometric changes in peri-implant defect treatments in animal models. Materials and Methods: An electronic search of four databases and a manual search of peer-reviewed journals for relevant articles were performed. Animal studies with data that compared the volumetric and/or histometric outcomes of peri-implant defect treatment with and without the use of BMP-2 were included. Meta-analyses were performed to analyze the weighted mean difference (WMD) and confidence interval (CI) for the recorded variables. Results: After completing the search process, 21 randomized controlled trials were included. The results of the meta-analyses showed that the WMD of bone-to-implant contact (%BIC) with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.50% (95% CI = 3.28% to 27.72%, P = .01) and 16.17% (95% CI = 11.17% to 21.16%, P < .00001), respectively, favoring the BMP-2 group. The WMD for the percentage of defect fill with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.88% (95% CI = 3.90% to 27.86%, P = .009) and 10.48% (95% CI = 0.95% to 20.02%, P = .03), respectively, favoring the BMP-2 group. The WMD for the vertical bone gain with 8 to 16 weeks of follow-up was 1.63 mm (95% CI = 0.58 to 2.67 mm, P = .002), also favoring the BMP-2 group. Conclusion: This review demonstrated that the use of BMP-2 in treating peri-implant defects showed better clinical and histometric outcomes than defects not treated with BMP-2 in animal models.

Study Design: Retrospective study., Objectives: To perform effectiveness and economic analyses using data from a retrospective study of patients who underwent XLIF surgery using tricalcium phosphate combined with iliac bone graft (TCP + IBG) or BMP-2 in Thailand., Methods: Data were collected from retrospective review of the medical charts and the spine registry of Siriraj Hospital, Bangkok, Thailand. The patients were divided into two groups (TCP + IBG group and BMP-2 group). Demographic, perioperative data, radiographic, clinical results, and quality of life related to health were collected and analyzed at 2-year follow-up. All economic data were collected during the perioperative period and presented as total charge, bone graft, implant/instrumentation, operative service, surgical supply, transfusion, medication, anesthesia, laboratory, and physical therapy., Results: Twenty-five TCP + IBG and 30 BMP-2 patients with spondylolisthesis and spinal stenosis as primary diagnosis were included. There were no significant differences in all demographic parameters (gender, age, underlying disease, diagnosis, and level of spine) between these two groups. During the perioperative period, the TCP + IBG group had more mean blood loss and more postoperative complications compared to the BMP-2 group. At 2 years of follow-up, there were no significant differences between the radiographic and clinical outcomes of the TCP + IBG and BMP-2 groups. The fusion rate for TCP + IBG and BMP-2 at 2 years of follow-up was 80% and 96.7%, respectively, and no statistically significant differences were observed. All clinical outcomes (Utility, Oswestry Disability Index, and EuroQol Visual Analog Scale) at 2-year follow-up improved significantly compared to preoperative outcomes, but there were no significant differences between the TCP + IBG and BMP-2 groups, either at preoperatively or at 2-year follow-up. The total charge of TCP + IBG was statistically significantly lower than that of BMP-2. Furthermore, the charges of TCP + IBG and BMP-2 during the perioperative period in Thailand were up to three times less than those in the United States., Conclusions: Using TCP + IBG as a standalone bone substitution for XLIF surgery with additional posterior instrumentation resulted in significantly lower direct medical charge compared to those using BMP-2 in the perioperative period. However, we could not detect a difference in the long-term radiographic and clinical outcomes of patients with TCP + IBG and BMP-2. These suggest that TCP + IBG may be a valuable alterative bone graft, especially in low- and middle-income countries., (© 2023. The Author(s).)

Leukocyte and platelet-rich fibrin is known to contain high concentrations of growth factors and when associated with rhBMP-2, it may increase bone remodeling due to its osteoinductive property. The aim of this case is to report the outcome of surgical treatment of medication-related osteonecrosis of the jaw with prototype plate installation and the use of leukocyte and platelet-rich fibrin in association with rhBMP-2 in a 78-year-old female patient under therapy with alendronate. The present Studies describes that the combination of this treatment presented complete healing of osteonecrosis and represents a promising treatment option to be used for medication-related osteonecrosis of the jaw., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

(1) Background : Since first approved by the FDA, on-label and off-label usage of recombinant human bone morphogenetic protein 2 (rhBMP2) for spinal fusion surgeries has become widespread. While many studies have investigated the safety and efficacy of its use, as well as its economic impact, few have looked at the current trends in its on- and off-label use. The goal of this study is to evaluate the current trends of on- and off-label rhBMP2 use for spinal fusion surgery. (2) Methods : A deidentified survey was created and electronically distributed to members of two international spine societies. Surgeons were asked to report their demographic information, surgical experience, and current usage of rhBMP2. They were then presented with five spinal fusion procedures and asked to report if they use rhBMP2 for these indications in their current practice. Responses were stratified between rhBMP2 users vs. non-users and on-label vs. off-label use. Data were analyzed using chi-square with Fisher's exact test for categorical data. (3) Results : A total of 146 respondents completed the survey with a response rate of 20.5%. There was no difference in overall rhBMP2 usage based on specialty, experience, or number of cases per year. Fellowship-trained surgeons and those who practice in the United States were more likely to use rhBMP2. Surgeons who were trained in the Southeast and Midwest regions reported the highest usage rates. rhBMP2 use was more common among fellowship-trained and US surgeons for ALIFs; non-US surgeons for multilevel anterior cervical discectomy and fusions; and fellowship-trained and orthopedic spine surgeons for lateral lumbar interbody fusions. Non-US surgeons were more likely to use rhBMP2 for off-label indications compared to surgeons from the US. (4) Conclusions : While various demographics of surgeons report different rates of rhBMP2 use, off-label use remains relatively commonplace amongst practicing spine surgeons.

Background: Bone morphogenetic protein 2 (BMP-2) is one of the most widely used biologics in spine surgery. Its osteoinductive properties have been shown since its inception to improve fusion rates. Despite the positive effects on promoting fusion, there remains concerns regarding the significant costs associated with its use. The goal of this review was to investigate the value of BMP-2 in spine surgery., Methods: A literature search was performed on various studies that report on the cost effectiveness and the value of BMP-2 in spine surgery. The value of BMP-2 was analyzed in two distinct settings: comparison to the gold standard iliac crest autograft and demineralized bone matrix. The value of BMP-2 was further analyzed in the setting of spinal deformity surgery., Results: The findings of our review determined that BMP-2 offers significant improvement in outcomes related to improvement of fusion rates and minimization of pseudoarthrosis and reoperations related to pseudoarthrosis and donor site morbidity from harvesting iliac crest bone graft. However, BMP-2 has been found to be significantly more expensive in comparison to iliac crest bone graft and other bone graft substitutes, which detracts from its positive value. In deformity surgery, BMP-2 is associated with improvement in fusion rates as well as reducing the rate of reoperations and pseudoarthrosis. These positive outcomes, however, are associated with an expensive upfront cost for BMP-2., Conclusions: In terms of value, BMP-2 is associated with improvement in quality outcomes related to a reduction in pseudoarthrosis and reoperations. It also leads to improved outcomes with a reduction in donor site morbidity associated with iliac crest bone graft harvest. However, the value of BMP-2 is negatively affected because of its significant costs. As a result, higher expense thresholds are needed to increase quality adjusted life years in patients who receive BMP-2. Further research investigating ways to minimize the costs associated with BMP-2 use can further improve its value in spine surgery.

Bone morphogenetic protein-2 (BMP-2) is used in the treatment of degenerative spinal disease and vertebral fractures, spine fusion, dental surgery, and facial surgery. However, high doses are associated with side effects such as inflammation and osteophytes. In this study, we performed spinal fusion surgery on mini-pigs using BMP-2 and a HA/β-TCP hydrogel carrier, and evaluated the degree of fusion and osteophyte growth according to time and dosage. Increasing the dose of BMP-2 led to a significantly higher fusion rate than was observed in the control group, and there was no significant difference between the 8-week and 16-week samples. We also found that the HA + β-TCP hydrogel combination helped maintain the rate of BMP-2 release. In conclusion, the BMP-2-loaded HA/β-TCP hydrogel carrier used in this study overcame the drawback of potentially causing side effects when used at high concentrations by enabling the sustained release of BMP-2. This method is also highly efficient, since it provides mineral matter to accelerate the fusion rate of the spine and improve bone quality.

Objective:  The aim of this study was to assess bone density, bone architecture and clinical function of canine nonunion distal appendicular long bone fractures with a defect treated with fixation, compression-resistant matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2)., Study Design:  Prospective cohort study with dogs at least 1-year post treatment. Computed tomography was performed and quantitative measurements from previous fracture sites were compared with measurements from contralateral limbs. Subjective evaluation included gait assessment and palpation., Results:  Six patients met the inclusion criteria. The rhBMP-2 treated bone exhibited higher density at the periphery and lower density in the centre, similar to the contralateral limb. All patients were weight bearing on the treated limb and all fractures were healed., Conclusion:  The rhBMP-2-treated bone underwent restoration of normal architecture and density. Acceptable limb function was present in all patients. The results of this study can serve as a basis for long-term response in treating nonunion fractures in veterinary patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: This review discusses success, time to healing, and complications of bone morphogenic proteins (BMPs) 7 and 2 in treating upper extremity nonunions., Methods: Systematic review identified 26 of 479 studies that met inclusion criteria. Publications described application of BMPs to acute and chronic upper extremity delayed unions/nonunions. Unions, complications, patient demographics, and fracture/healing patterns were pooled and analyzed., Results: Nonunions treated with BMP-7 (n=302) involved the humerus (64%), forearm (22%), clavicle (11%), and hand/wrist (3%), with prior surgical correction attempted in 84%. Nonunions treated with BMP-2 (n=96) involved the humerus (58%), hand/wrist (27%), forearm (14%), and clavicle (1%), with prior surgical correction attempted in all. Most nonunions (80%) were present for over 12 months before BMP application. Union rates of BMP-7 varied according to site: hand/wrist (95%), humerus (74%), forearm (29%), and clavicle (6.2%) nonunions achieved union as defined by study authors in 232 days (confidence interval=96-369, Q <0.001) on average. While not significant across studies, BMP-2 union rates were 71% of hand/wrist and 75% of humerus nonunions. Comparison of the BMPs demonstrates different proportions of success in humerus and hand/wrist fractures ( P <.001) but not forearm fractures ( P <.77) and longer time to radiographic union with BMP-7 ( P <.011)., Conclusions: Most hand/wrist and humerus nonunions treated with BMP-7 and BMP-2 achieved union, with significant similarity among BMP-7 studies not observed in BMP-2 studies. Nonunions treated with BMP-7 have longer healing times yet similar complication rates compared with BMP-2. Overall, BMPs are an effective adjunct to fracture healing with acceptable complication profile.

Background: There is still a lack of credible evidence in the literature regarding the effectiveness of recombinant human bone morphogenetic protein 2 (rhBMP-2) in bone regeneration of alveolar bone defects. Therefore, the purpose of this study is to evaluate the efficacy and safety of rhBMP-2 in autogenous bone graft in bone regeneration of alveolar bone defects and to provide basis for clinical practice., Methods: As of March 2023, two independent investigators will identify target literature by searching seven major databases (EMBASE, Google Scholar, PubMed, Cochrane Library, Wan Fang, CNKI, and Web of Science). All clinical cohort studies evaluating the efficacy of rhBMP-2 will be included. The outcomes of the study include changes in the depth of the dental pocket at the involved site, increased clinical attachment levels, patient satisfaction, and adverse events. The Cochrane risk of bias tool will be independently used to evaluate the risk of bias of included randomized cohort studies by two reviewers. A modified version of the Downs and Black tool is adopted to evaluate the quality of nonrandomized cohort studies., Results: We hypothesized that rhBMP-2 plays an active role in bone regeneration in alveolar bone defects., Conclusions: It is worthy to critically review the evidence of the assessment of rhBMP-2 to inform clinical practice., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The study aimed to explore the feasibility of a nanodrug delivery system to treat open fractures with bone defects. We developed a cefazolin (Cef)/bone morphogenetic protein 2 (BMP-2)@mesoporous silica nanoparticle (MSN) delivery system; meanwhile, Cef/MBP-2@ poly(lactic-co-glycolic acid) (PLGA) was also developed as control. For the purpose of determining the osteogenic and anti-inflammatory actions of the nanodelivery system, we cultured bone marrow mesenchymal stem cells (BMSCs) and constructed a bone defect mouse model to evaluate its clinical efficacy. After physicochemical property testing, we determined that MSN had good stability and did not easily accumulate or precipitate and it could effectively prolong the Cef's half-life by nearly eight times. In BMSCs, we found that compared with the PLGA delivery system, MSNs better penetrated into the bone tissue, thus effectively increasing BMSCs' proliferation and migration ability to facilitate bone defect repair. Furthermore, the MSN delivery system could improve BMSCs' mineralization indexes (alkaline phosphatase [ALP], osteocalcin [OCN], and collagen I [Col I]) to effectively improve its osteogenic ability. Moreover, the MSN delivery system could inhibit inflammation in bone defect mice, which was mainly reflected in its ability to reduce the release of IL-1 β and IL-4 and increase IL-10 levels; it could also effectively reduce apoptosis of CD4 + and CD8 + T cells, thus improving their immune function. Furthermore, the percentage of new bones, bone mineral density, trabecular volume, and trabecular numbers in the fracture region were improved in mice treated with MSN, which allowed better repair of bone defects. Hence, Cef/BMP-2@MSN may be feasible for open fractures with bone defects., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Mingkui Shen et al.)

Objective: To explore the effectiveness and feasibility of injectable Escherichia coli-derived recombinant human bone morphogenetic protein-2 (injectable E-rhBMP-2, a combination of E. coli-derived recombinant human bone morphogenic protein-2 and a hydrogel type beta-tricalcium phosphate carrier) as a bone substitute for anterior lumbar interbody fusion (ALIF) of the lumbosacral junction in adult spinal deformity (ASD) patients., Methods: A prospective single-institution therapeutic exploratory trial was conducted. Twenty patients (average age: 69.1 years; 19 female and one male; average fusion level: 7.95) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including ALIF at the lumbosacral junction from December 2017 to January 2019 were evaluated. Injectable E-rhBMP-2 was prepared by dissolving 3 mg of E. coli-derived recombinant human bone morphogenetic protein-2 in 1.5 ml H 2 O and mixing in situ with 9 g hydrogel type beta-tricalcium phosphate. This bone graft substitute was loaded onto a metal ALIF cage and L 5 -S 1 ALIF was performed in routine manner. Then posterior column osteotomy with multilevel oblique lumbar interbody fusion or pedicle subtraction osteotomy with accessory rod technique was performed to restore sagittal balance. Patients were followed up for 12 months. CT-based fusion rates were examined at 6 and 12 months after surgery. Also, clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] score of the back and leg) were evaluated at 6 and 12 months after surgery. All postoperative adverse events were evaluated for the association with injectable E.BMP-2., Results: Of the 20 patients, loss to follow-up occurred with one patient at 6 months after surgery and one patient at 12 months after surgery, resulting in a total of 18 patients who were available for follow-up. Six months after surgery, 68.4% patients achieved solid fusion. Twelve months after surgery, 100% fusion rate was achieved. Compared to baseline values, ODI scores improved to 45.8% and 63.7%, VAS (back) improved to 69.2% and 72.8%, and VAS (leg) improved to 49.2% and 64.8%, respectively, at 6 and 12 months after surgery (p < 0.001 for all). Ten cases of adverse events occurred. But no adverse events were associated with injectable E-rhBMP-2., Conclusion: Injectable E-rhBMP-2 will be an effective bone graft substitute when achieving solid interbody fusion in the lumbosacral junction., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

The objective of this umbrella review was to determine the effectiveness of rhBMP-2 in the reconstructive surgery of cleft patients through an evaluation of bone filling and volume of newly formed bone in the cleft area. A systematic search was carried out in PubMed/ Medline, Scopus, Cochrane Database of Abstracts of Reviews of Effects (DARE), Latin American and Caribbean Health Sciences Literature (LILACS), and the System for Information on Grey Literature in Europe (SIGLE) via Open Grey, until June 2020. Risk of bias was assessed using the ROBIS tool. A total of 2739 articles were identified and, based on the inclusion and exclusion criteria, six were included for final evaluation. The bone filling rate was 74.23% in the rhBMP-2 group and 72.38% in the autogenous group. Regarding the risk of bias, none of the articles had a low risk, four had an uncertain risk, and two a high risk. The results of this umbrella review show that the studies had high and uncertain risks of bias, and high heterogeneity. There was a lack of evidence regarding the possible complications offered by this therapy. The recommendation to use BMP-2 for alveolar cleft reconstruction, especially in a paediatric population, should be viewed with caution. New primary studies are needed to assess this variable and safely determine the use of rhBMP-2 in reconstructive surgery for cleft patients., Competing Interests: Conflict of interest We have no conflicts of interest., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Study Design: Retrospective Database Study., Objective: Investigate utilization of bone morphogenetic protein (BMP-2) between 2004 and 2014., Summary of Background Data: The utilization, particularly off-label utilization, of BMP-2 has been controversial and debated in the literature. Given the concerns regarding cancer and potential complications, the risk benefit profile of BMP must be weighed with each surgical case. The debate regarding the costs and potential side effects of BMP-2 compared with autologous iliac crest bone harvest has continued., Methods: The National Inpatient Sample (NIS) database was queried for the use of BMP-2 (ICD-9-CM 84.52) between 2004 and 2014 across 44 states. The NIS database represents a 20% sample of discharges, weighted to provide national estimates. BMP-2 utilization rates in spine surgery fusion procedures were calculated as a fraction of the total number of thoracic, lumbar, and sacral spinal fusion surgeries performed each year., Results: Between 2004 and 2014, BMP-2 was utilized in 927,275 spinal fusion surgeries. In 2004, BMP-2 was utilized in 28.3% of all cases (N=48,613). The relative use of BMP-2 in spine fusion surgeries peaked in 2008 at 47.0% (N=112,180). Since then, it has continued to steadily decline with an endpoint of 23.6% of cases in 2014 (N=60,863)., Conclusions: Throughout the United States, the utilization of BMP-2 in thoracolumbar fusion surgeries increased from 28.3% to 47.0% between 2004 and 2008. However, from 2008 to 2014, the utilization of BMP-2 in thoracolumbar spine fusion surgeries decreased significantly from 47.0% to 23.4%. While this study provides information on the utilization of BMP-2 for the entire United States over an 11-year period, further research is needed to the determine the factors affecting these trends., Competing Interests: C.S. has stocks in Vertera Acquisition by Nuvasive and in Gilead. Z.S. has speaking/teaching arrangements with Medtronic and Stryker. A.J.P. has consulted for Globus Medical, United Healthcare and Medtronic. He has also received royalties from Globus Medical. V.M.A. had consulted for Medtronic, Stryker, Zimmer, Camber Spine, Spine Up, Johnson and Johnson and NuVasive. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background Context: Arthrodesis is important for the success of posterior cervical fusion (PCF), however, there exists limited data regarding the safety and efficacy of bone morphogenic protein (BMP) in PCF., Purpose: The primary objective was to evaluate early postoperative complications associated with BMP in PCF and determine whether BMP leads to adverse early clinical outcomes. A secondary objective was to determine the optimal location for BMP sponge placement, within the facet joint (IF) or elsewhere, and the optimal dosage/level., Design: Retrospective, consecutive case-control study., Patient Sample: Seven hundred sixty-five patients who underwent PCF OUTCOME MEASURES: Patient-reported outcomes (PROs), complications, arthrodesis, optimum dose/level of BMP METHODS: Surgical data, including preoperative diagnosis, levels fused, type of bone graft, BMP dose (when used), and fusion technique were recorded. Complications were assessed by reviewing the medical record encompassing the first 6-weeks postoperative. These included medical, neurological, and wound-related complications and reoperation. Neurological complications were defined as any new weakness, radicular pain, or numbness. PROs were collected, including SF36, VAS, EQ-5D, and NDI scores. To determine the optimal dosage and location for BMP placement, a sub-analysis was performed., Results: There were no significant differences between the BMP and no BMP group with regards to wound complications, neurological complications, or reoperation. There were no differences in PROs between BMP and no BMP. Placement of BMP for IF and at a dose of 0.87 mg/level minimized wound-related complications. The BMP group had a higher fusion rate compared to the no BMP group (96% vs. 91%, p=.02) when assessed 1 year post-operatively., Conclusion: BMP was not associated with a higher rate of early complications after PCF when the dose was minimized. Complications thought to be associated with BMP, such as compressive seroma, radiculitis, and wound-related complications were not seen at a higher rate. PROs at early follow-up were similar. Placement of BMP for IF and at lower doses than previously reported may minimize complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Objectives: To determine the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) with hydroxyapatite (HA) carrier augmentation in managing critical-sized bone defect (CSBD) with induced membrane technique (IMT)., Design: Retrospective comparative study., Setting: Academic level I trauma center., Patients/participants: The study included 14 patients who underwent rhBMP-2 with HA carrier (rhBMP-2/HA) augmentation in IMT for managing CSBD (BMP group). Moreover, 14 patients who underwent IMT without rhBMP-2 augmentation were matched by propensity score analysis (non-BMP group)., Intervention: IMT with or without rhBMP-2/HA augmentation., Main Outcome Measurement: Changes in quality and quantity measurements of grafted bone to regenerated bone using serial computed tomography., Results: In the BMP and non-BMP groups, the changes in densities from grafted bone to regenerated bone were +379.63 Hounsfield unit and +248.55 Hounsfield unit (P = 0.034), changes in dense bone percentage were +37.52% and +23.31% (P = 0.027), corticalization rates under the plate were 79.70% and 39.30% (P = 0.007), changes in volume were -20.77% and -23.35% (P = 0.812), union rates were 85.71% and 78.57% (P = 0.622), numbers of patients requiring additional procedures were 4 and 3 (P = 0.663), and time to union were 316.3 and 585.45 days (P = 0.040), respectively., Conclusions: RhBMP-2/HA augmentation increases the density of regenerated bone, enhances corticalization under the plate, and shortens the time to union while managing CSBD with IMT., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To assess long-term outcomes of implants placed in conjunction with guided bone regeneration (GBR) with or without recombinant human bone morphogenetic protein-2 (rhBMP-2)., Materials and Methods: Eleven patients with at least two lateral bone defects (split-mouth design) received a total of 34 implants. The defects were treated with a xenogenic bone substitute with (test) or without (control) rhBMP-2 and covered with a collagen membrane. Eight patients could be reexamined after at least 17 years. Wilcoxon signed-rank tests were performed to assess differences between test and control groups., Results: The implant survival rate was 100% for all test and control sites. Mean marginal bone levels were 2.51 mm (SD ±1.64) (mesial test), 1.83 mm (SD ±0.93) (mesial control) (p = .055), 2.36 mm (SD ±1.70) (distal test), and 2.13 mm (SD ±0.84) (distal control) (p = 1.000). Compared with the mean values at baseline, a mean bone loss of 1.16 mm (SD ±1.60) (test) and 0.70 mm (SD ±1.02) (control) was found. The mean buccal bone gain after 17 years was 5.38 mm (test) and 3.14 mm (control) based on the comparison between the measurements at the cone beam CT after 17 years and the data from the intraoperative measurements at baseline. Further, mean values for (i) bone thickness ranged from 1.36 to 3.09 mm (test) and 1.18 to 3.39 mm (control) and for (ii) mucosal thickness of 1.24 mm (test) and 1.26 mm (control)., Conclusion: Implants placed in conjunction with GBR applying a xenogenic bone substitute and a collagen membrane with and without the addition of rhBMP-2 demonstrate excellent clinical and radiographic results after at least 17 years., (© 2021 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Study Design: A retrospective study., Objective: The aim of this study was to evaluate the clinical and radiographic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in pars repair of lumbar spondylolysis., Summary of Background Data: BMP-2 is a growth factor that plays a role in the formation of bone and promotes bone healing. However, few studies of using rhBMP-2 in pars repair have been reported., Methods: Direct pars repair and pedicle screw fixation was performed, which were added with 1 mg of rhBMP-2 and iliac crest bone graft in the study group (rhBMP-2 group, n=32) and iliac crest bone graft alone in the autograft group (n=36). Patients completed the visual analog scale and the Oswestry Disability Index preoperation, 3, 6, and 12 months after the operation. Computed tomography scans with axial and sagittal reconstructions were performed at 6, 9, 12, 18, and 24 months postoperatively., Results: Baseline demographic data showed no significant difference between 2 groups. There were significant differences for the Oswestry Disability Index score at 3 and 6 months postoperatively, which were higher in the autograft group. There was no significant difference between the groups with respect to the overall union status. As for union speed, the trabecular bone appeared earlier and union rates were higher in rhBMP-2 group than in the autograft group at 9, and 12 months postoperatively. No complications were identified in either group. One case in the rhBMP-2 group and 2 cases in the autograft group underwent revision surgery., Conclusion: Compared with iliac crest bone graft alone, the use of rhBMP-2 can accelerate fusion in pars repair for young patients with spondylolysis. The union rates were significantly different at 9 and 12 months after surgery. This study showed no clinical difference when adding rhBMP-2 compared with iliac crest bone graft alone., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To conduct an animal experimental study to evaluate the safety and efficacy of the compression-resistant matrix (CRM) carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2) in osteogenesis., Material and Methods: New moldable CRM carrier, and with rhBMP-2 (new CRM carrier with rhBMP-2) were prepared as the experimental groups. Pre-existing synthetic bone graft material was prepared as a control graft group. A total of 24 rabbits were included in the study. Defects were made and grafts were performed, and radiographic and histopathologic findings were evaluated to assess fusion., Results: In the computed tomographic scan, new bone formation was superior in 16.0%, 39.3%, 64.7%, and 81.1% of the total defect volume at 4, 8, 12, and 16 weeks in the new CRM carrier with rhBMP-2 group. In the new CRM carrier group, new bone formation was observed in 10.6%, 26.3%, 53.1%, and 71.4%, respectively. In the control graft group, new bone formation was observed in 10.1%, 26.6%, 53.4%, and 72.1%, respectively. On histopathologic evaluation, new CRM carrier with rhBMP-2 group showed better new bone formation compared with those of other groups., Conclusion: The new moldable CRM carrier and the CRM carrier with rhBMP-2 showed preclinical safety and efficacy in new bone formation. In particular, the CRM carrier with rhBMP-2 was considered to be an effective bone graft material for bone fusion.

With an increasing elderly population worldwide, the incidence of spine degenerative diseases with neck and shoulder pain as the main symptom is rising obviously, which has now become one of the important and difficult problems in sociomedical science. This study was to explore the effects of different ratios of recombinant human bone morphogenetic protein-2 (rhBMP-2) compound to the autogenous bone on cervical interbody fusion. 90 cervical degeneration patients with the need of surgical treatment admitted to our hospital from January 2019 to January 2020 were selected as the research objects and equally divided into group A, group B, and group C according to the order of admission, with 30 cases in each group and the ratios of rhBMP-2 compound to autogenous bone being 2 : 1, 1 : 1, and 1 : 2 respectively, and standard anterior cervical diskectomy and fusion (ACDF) treatment was performed to all patients to compare their surgery-related indexes, the Japanese Orthopaedic Association (JOA) score, the visual analog scale (VAS) score, the effect of cervical interbody fusion, and the postoperative complication rate (CR). Compared with group A and group C, group B achieved the significantly better surgery-related indexes ( P < 0.05), significantly higher postoperative JOA scores ( P < 0.05), significantly lower postoperative neck and upper limb VAS scores ( P < 0.05), significantly better effect of cervical interbody fusion ( P < 0.05), and significantly lower postoperative CR ( P < 0.05). 1 : 1 is the best ratio of rhBMP-2 compound to the autogenous bone, for it can optimize patients' perioperative indexes, reduce the postoperative pain, lower the possibility of complications, and improve the effect of cervical interbody fusion, which should be promoted and applied in practice., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Xinzhu Zhang et al.)

The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in the past 20 years. Most studies reported that such agents, used in different concentrations, doses and combined with various scaffolds, might promote periodontal tissue regeneration, but evidence for the most effective combination of such agents is lacking. The objective of this study 13 was to rank the different combinations of recombinant human-derived growth and differentiation factors with/without scaffold biomaterial in the treatment of periodontal intrabony defects, through network meta-analysis of pre-clinical studies. The systematic review and network meta-analysis protocol was registered on the PROSPERO Systematic Review database with reference number: CRD42021213673. Relevant published articles were obtained after searching five electronic databases. A specific search strategy was followed by using keywords related to intrabony defects, regenerative materials, scaffolds and recombinant factors, and animal studies. All pre-clinical studies used for periodontal regeneration were included. The primary outcomes were: regeneration of junctional epithelium (mm), new cementum, connective tissue attachment, percentage of new bone formation (%), bone area (mm 2 ), bone volume density (g/cm 3 ) and bone height (mm) data was extracted. The analysis was carried out using network meta-analysis methods, that is illustrating network plots, contribution plots, predictive and confidence interval plot, surface under the cumulative ranking (SUCRA), multidimensional scale ranking and net funnel plots using STATA IC statistical software. An SYRCLE's tool for assessing risk of bias was used for reporting risk of bias among individual studies. A total of N = 24 for qualitative and N = 21 studies for quantitative analysis published till 2020 were included. The cumulative total number of animals included in the control and test groups were N = 162 and N = 339, respectively. The duration of the study was between 3 and 102 weeks rhBMP-2 ranked higher in SUCRA as the agent associated with the best performance for bone volume density. rhGDF-5/TCP ranked best in the bone area (mm2), rhPDGF-BB/Equine ranked best in bone height (mm), rhBMP-2 ranked best in the percentage of new bone fill, rhBMP-2/ACS ranked best in new cementum formation, and rhGDF-5/b- TCP/PLGA ranked best in connective tissue attachment and junctional epithelium. There were no adverse effects identified in the literature that could affect the different outcomes for regeneration in intrabony defects. Various recombinant factors are effective in promoting the regeneration of both soft and hard tissue supporting structures of the periodontium. However, when considering different outcomes, different agents, associated or not with biomaterials, ranked best. Keeping into account the limited transferability of results from animal studies to the clinical setting, the choice of the most appropriate formulation of bioactive agents may depend on clinical needs and purpose., (© 2021 John Wiley & Sons Ltd.)

Background: The objectives of this study were to build upon previously-reported 12-month findings by retrospectively comparing 24-month follow-up hospitalization charges and potentially-relevant readmissions in US lumbar fusion surgeries that employed either recombinant human bone morphogenetic protein-2 (rhBMP-2) or a cellular bone allograft comprised of viable lineage-committed bone cells (V-CBA) via a nationwide healthcare system database., Methods: A total of 16,172 patients underwent lumbar fusion surgery using V-CBA or rhBMP-2 in the original study, of whom 3,792 patients (23.4%) were identified in the current study with all-cause readmissions during the 24-month follow-up period. Confounding baseline patient, procedure, and hospital characteristics found in the original study were used to adjust multivariate regression models comparing differences in 24-month follow-up hospitalization charges (in 2020 US dollars) and lengths of stay (LOS; in days) between the groups. Differences in potentially-relevant follow-up readmissions were also compared, and all analyses were repeated in the subset of patients who only received treatment at a single level of the spine., Results: The adjusted cumulative mean 24-month follow-up hospitalization charges in the full cohort were significantly lower in the V-CBA group ($99,087) versus the rhBMP-2 group ($124,389; P < 0.0001), and this pattern remained in the single-level cohort (V-CBA = $104,906 vs rhBMP-2 = $125,311; P = 0.0006). There were no differences between groups in adjusted cumulative mean LOS in either cohort. Differences in the rates of follow-up readmissions aligned with baseline comorbidities originally reported for the initial procedure. Subsequent lumbar fusion rates were significantly lower for V-CBA patients in the full cohort (10.12% vs 12.00%; P = 0.0002) and similar between groups in the single-level cohort, in spite of V-CBA patients having significantly higher rates of baseline comorbidities that could negatively impact clinical outcomes, including bony fusion., Conclusions: The results of this study suggest that use of V-CBA for lumbar fusion surgeries performed in the US is associated with substantially lower 24-month follow-up hospitalization charges versus rhBMP-2, with both exhibiting similar rates of subsequent lumbar fusion procedures and potentially-relevant readmissions., (© 2021. The Author(s).)

Concentrated growth factor (CGF) is 100% blood-derived, cross-linked fibrin glue with platelets and growth factors. Human CGF clot is transformed into membrane by a compression device, which has been widely used clinically. However, the mechanical properties of the CGF membranes have not been well characterized. The aims of this study were to measure the tensile strength of human CGF membrane and observe its behavior as a scaffold of BMP-2 in ectopic site over the skull. The tensile test of the full length was performed at the speed of 2mm/min. The CGF membrane (5 × 5 × 2 mm 3 ) or the CGF/BMP-2 (1.0 μg) membrane was grafted onto the skull periosteum of nude mice (5-week-old, male), and harvested at 14 days after the graft. The appearance and size of the CGF membranes were almost same for 7 days by soaking at 4 °C in saline. The average values of the tensile strength at 0 day and 7 days were 0.24 MPa and 0.26 MPa, respectively. No significant differences of both the tensile strength and the elastic modulus were found among 0, 1, 3, and 7 days. Supra-periosteal bone induction was found at 14 days in the CGF/BMP-2, while the CGF alone did not induce bone. These results demonstrated that human CGF membrane could become a short-term, sticky fibrin scaffold for BMP-2, and might be preserved as auto-membranes for wound protection after the surgery.

Recent studies have indicated the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to be a viable adjunctive to alveolar cleft reconstruction owing to its osteoinductive capacity. This study aimed to evaluate the efficacy of rhBMP-2 in the treatment of alveolar cleft with autologous bone grafts by precise volumetric analysis. Twenty-six patients (aged 8-14) with unilateral alveolar clefts were enrolled in this comparative study. Patients were divided into two groups: the iliac crest bone graft (ICBG) was placed at the side of the cleft in the control group (ICBG group), and rhBMP-2 was mixed with the ICBG in the rhBMP-2 group (BMP group). Helical computed tomographic images were obtained preoperatively and 12 months postoperatively. The datasets were reconstructed as three-dimensional (3D) images using Mimics software and processed using Geomagic Wrap. The newly formed bone of the alveolar cleft was segmented by identifying the differences between preoperative and postoperative 3D images. In the ICBG group, the volume of newly formed bone ranged from 0.25 to 0.88 cm 3 , and the mean (SD) bone formation percentage was 42.01% (15.57%). In the BMP group, the volume of newly formed bone ranged from 0.34 to 1.09 cm 3 , and the bone formation mean (SD) percentage was 55.79% (11.84%). There was a statistically significant difference between the two groups in terms of the postoperative percentage of bone formation (p = 0.022). Thus, rhBMP-2 combined with an autologous bone graft is a promising technique to improve the results of secondary alveolar bone grafting., (Copyright © 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

In aged individuals, osteopenia is a great concern for achieving solid spinal fusion. Spinal malunion could lead to various implant-related complications and reduce postoperative quality of life. This study aims to investigate the efficacy of collagen-binding bone morphogenetic protein-2 (CBD-BMP-2) on the treatment of lumbar inter-transverse defects and to explore whether platelet-rich plasma could help CBD-BMP-2 to achieve a better outcome in terms of osteogenesis in senile rats with osteopenia. In vitro experiment proved the angiogenic function of platelet-rich plasma and osteogenic effect of CBD-BMP-2. Rats were performed posterolateral lumbar inter-transverse fusion. Rats implanted with CBD-BMP-2 + platelet-rich plasma were assigned to Group A ( n  = 20), rats implanted with CBD-BMP-2 were assigned to Group B ( n  = 20), and those with platelet-rich plasma were assigned to Group C ( n  = 20). Four weeks after implantation, radiographic assessment, manual palpation, and histological evaluation were performed. In vivo experiments showed satisfactory therapeutic effect on lumbar inter-transverse fusion in both Groups A and B and better results of bone microarchitecture in Group A. Solid fusion rate was 77.8% in Group A, 66.7% in Group B, and 0% in Group C ( P  < 0.001). Our study indicated that CBD-BMP-2 could effectively facilitate the lumbar inter-transverse fusion in aged rats with osteopenia and platelet-rich plasma could help CBD-BMP-2 to enhance the bone healing of vertebral defects.

Bone fracture is a major contributor to debilitation and death among patients with bone diseases. Thus, osteogenic protein therapeutics and their delivery to bone have been extensively researched as strategies to accelerate fracture healing. To prevent morbidity and mortality of fractures, which occur frequently in the aging population, there is a critical need for development of first-line therapeutics. Bone morphogenic protein-2 (BMP-2) has been at the forefront of bone regeneration research for its potent osteoinduction, despite safety concerns and biophysiological obstacles of delivery to bone. However, continued pursuit of osteoinductive proteins as a therapeutic option is largely aided by drug delivery systems, playing an imperative role in enhancing safety and efficacy. In this work, we highlighted several types of drug delivery platforms and their biomaterials, to evaluate the suitability in overcoming challenges of therapeutic protein delivery for bone regeneration. To showcase the clinical considerations for each type of platform, we have assessed the most common route of administration strategies for bone regeneration, classifying the platforms as implantable or injectable. Additionally, we have analyzed the commonly utilized models and methodology for safety and efficacy evaluation of these osteogenic protein-loaded systems, to present clinical opinions for future directions of research in this field. It is hoped that this review will promote research and development of clinically translatable osteogenic protein therapeutics, while targeting first-line treatment status for achieving desired outcomes of fracture healing. Graphical abstract.

Purpose: This retrospective study examined distal bone healing on the adjacent second molar between the demineralized bone matrix incorporated with recombinant human bone morphogenetic protein-2 (DBM/rhBMP-2) and a collagen sponge in the mandibular third molar extraction socket., Materials and Methods: From 2018 to 2020, 26 extraction patients (male, average 21.5 years), who received a graft (each of 13 using DBM/rhBMP-2 and collagen plug, respectively) on the extraction socket without primary closure, were enrolled in this study. The bony defect was measured by computed tomography before and 6 months after the extraction. The difference in the bone healing was analyzed between the DBM/rhBMP-2 and collagen plug groups using a Mann-Whitney U test., Results: No complications, such as infection and food packing, were encountered. The DBM/rhBMP-2 and collagen plug groups showed a similar distribution of preoperative bony defect (median 5.8 and 5.0 mm, respectively). After 6 months, more bone healing was observed in the DBM/rhBMP-2 group than in the collagen plug group (median 3.85 and 2.37 mm, respectively, P = .029) CONCLUSIONS: A DBM/rhBMP-2 graft after a third molar extraction does significantly alter the bony defect on the distal aspect of the second molar compared with a collagen plug., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Infection and delayed wound healing are two major serious complications related to traumatic injuries and cause a significant burden to patients and society. Most currently available drug delivery materials typically carry a single drug, lack protection from drug loading, and face challenges in on-demand and precisely controlled drug release. Here, we report a flower ( Cirsium arvense )-inspired capsule-integrated multilayer nanofilm (FICIF), synthesized using a layer-by-layer self-assembly, for programmed multiple drug co-delivery for trauma (open fracture as an example) treatments. Our approach allows polypeptide multilayer nanofilms and innovative impregnated capsules to assemble hierarchical reservoirs with specific drug binding sites, shielding protection capability, and ordered packing structures. The resultant FICIF nanocarriers enable sustained and on-demand co-delivery of a unique immune-tuning cytokine (interleukin 12p70) and a growth factor (bone morphogenetic protein 2) in clinical use, resulting in extraordinary anti-infection (3 orders of magnitude improved bacterial killing) and bone regeneration (5 times enhanced bone healing) in treating infected rat femur fractures. The successful synthesis of these biomimetic high-performance delivery nanocoatings is expected to serve as a source of inspiration for the development of biomaterials for various clinical applications.

Tissue engineering using adult human mesenchymal stem cells (MSCs) seeded within biomaterial scaffolds has shown the potential to enhance bone healing. Recently, we have developed an injectable, biodegradable methacrylated gelatin-based hydrogel, which was especially effective in producing scaffolds in situ and allowed the delivery of high viable stem cells and gene vehicles. The well-demonstrated benefits of recombinant adeno-associated viral (rAAV) vector, including long-term gene transfer efficiency and relative safety, combination of gene and cell therapies has been developed in both basic and translational research to support future bone tissue regeneration clinical trials. In this study, we have critically assessed the applicability of single-step visible light (VL) photocrosslinking fabrication of gelatin scaffold to deliver rAAV encoding human bone morphogenetic protein-2 (BMP-2) gene to address the need for sustained BMP-2 presence localized within scaffolds for the repair of cranial bone defect in mouse model. In this method, rAAV-BMP-2 and human bone marrow-derived MSCs (hBMSCs) were simultaneously included into gelatin scaffolds during scaffold formation by VL illumination. We demonstrated that the subsequent release of rAAV-BMP-2 constructs from the scaffold matrix, which resulted in efficient in situ expression of BMP-2 gene by hBMSCs seeded within the scaffolds, and thus induced their osteogenic differentiation without the supplement of exogenous BMP-2. The reparative capacity of this novel stem cell-seeded and gene-activated scaffolds was further confirmed in the cranial defect in the severe combined immunodeficiency mice, revealed by imaging, histology, and immunohistochemistry at 6 weeks after cranial defect treatment., (© 2020 The Authors. STEM CELLS Translational Medicine published by Wiley Periodicals LLC on behalf of AlphaMed Press.)