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To analyze the tissue morphology around implant-supported prostheses by digital technology and to evaluate the effect of prosthetic contours on the changes in tissues following the free gingiva graft procedure.A total of 53 implants in 32 patients receiving free gingiva grafts were selected. These had previously presented insufficient keratinized mucosa width (KMW). At the follow-up visits (mean: 16.66 ± 9.97 months), the implant position and tissue condition were documented with an oral scanner. Vertical soft tissue thickness (VT), measured from the implant-abutment connection to the marginal tissues, and horizontal soft tissue thickness (HT), at the level of the platform, were calculated. The VT, HT, and emergence angle (EA) of prostheses were assessed by 3Shape analyzing software. The final KMW was measured by clinical assessment. Marginal bone loss (MBL) was calculated in the follow-up bitewing radiographs.The mean VT in the study was 2.65 ± 0.75 mm at the mid-buccal sites, 3.74 ± 1.22 mm at the mesial, 3.16 ± 1.08 mm at the distal, and 2.53 ± 0.92 at the mid-lingual aspects. The mid-buccal HT was 1.45 ± 0.53 mm while the mid-lingual was 1.05 ± 0.43 mm (p = 0.008). Interestingly, prostheses with mid-buccal EAFree gingival grafting is a predictable treatment approach to augmenting soft tissue 3-dimensionally. Prostheses with EA

BACKGROUND To date, a reliable, validated pain-level assessment approach to evaluate consciousness status has yet to be established. With appropriate algorithms, computers can learn to detect patterns and associations in large datasets. OBJECTIVE This study aimed to apply machine learning to electrocardiography (ECG) waveforms to create an algorithm to predict and monitor regular uterine contraction cycle-induced labor pain. METHODS Pregnant women undergoing natural spontaneous delivery (NSD) with regular uterine contraction pain were recruited from National Taiwan University Hospital for prospective data collection and cross-sectional analysis. Machine learning was used to fine-tune a nociception-related algorithm (NoP) based initially on the complex analysis of features in high-fidelity ECG waveform recordings in 4 pregnant women. The algorithm was then validated in another 12 pregnant women. Data on uterine contractions were collected as raw data from tocometry and ECG waveforms by re-cording simultaneously using the same computer. Every uterine contraction cycle with VAS pain score was also confirmed and recorded by an investigating nurse for further analysis. RESULTS The machine learning model that most accurately predicted pain was the XGBoost model, which exhibited the highest ROC (0.98), followed by the random forest and GBDT models with an ROC of 0.89. NoP threshold values and NoP indexes were the highest and most important features in the XGBoost models. CONCLUSIONS The newly developed algorithm supports obstetricians in clinical practice by providing early detection of alterations in ECG waveforms during uterine contraction cycles. The integration of ECG systems should be considered in artificial intelligence (AI) models for future parturient care.

This study evaluated the mid-term (12-month) biomechanical, biocompatibility, and biological performance of additive-manufactured bioabsorbable iron-based interference screws (ISs). Two bioabsorbable iron IS types—manufactured using pure iron powder (iron_IS) and using pure iron powder with 0.2 wt% tricalcium phosphate (TCP_IS)—were compared with conventional metallic IS (control) using in vitro biocompatibility and degradation analyses and an in vivo animal study. The in vitro ultimate failure strength was significantly higher for iron_IS and TCP_IS than for control ISs at 3 months post-operatively; however, the difference between groups were nonsignificant thereafter. Moreover, at 3 months after implantation, iron_IS and TCP_IS increased bone volume fraction, bone surface area fraction, and percent intersection surface; the changes thereafter were nonsignificant. Iron_IS and TCP_IS demonstrated degradation over time with increased implant surface, decreased implant volume, and structure thickness; nevertheless, the analyses of visceral organs and biochemistry demonstrated normal results, except for time-dependent iron deposition in the spleen. Therefore, compared with conventional ISs, bioabsorbable iron-based ISs exhibit higher initial mechanical strength. Although iron-based ISs demonstrate high biocompatibility 12 months after implantation, their corrosive iron products may accumulate in the spleen. Because they demonstrate mechanical superiority along with considerable absorption capability after implantation, iron-based ISs may have potential applications in implantable medical-device development in the future.

Objective Our aim is to examine the mechanical properties of two types of additive manufactured hollow porous dental implants and 6 and 12-week bone ingrowth after insertion in animals. A 3D numerical model is also developed to show detailed tissue differentiation and to provide design guidelines for implants. Methods The two porous and a commercial dental implant were studied by series of in vitro mechanical tests (three-point bending, torsional, screwing torque, and sawbone pull-out tests). They also evaluated by in vivo animal tests (micro-CT analysis) and ex vivo pull-out tests. Moreover, the mechano-regulation algorithm was implemented by the 3D finite element model to predict the history of tissue differentiation around the implants. Results The results showed that the two porous implants can significantly improve osseointegration after 12-week bone healing. This resulted in good fixation and stability of implants, giving very high maximum pull-out strength 413.1 N and 493.2 N, compared to 245.7 N for the commercial implant. Also, several features were accurately predicted by the mechano-regulation model, such as transversely connected bone formation, and bone resorption occurred in the middle of implants. Significance Systematic studies on dental implants with multiple approaches, including new design, mechanical tests, animal tests, and numerical modeling, were performed. Two hollow porous implants significantly improved bone ingrowth compared with commercial implants, while maintaining mechanical strength. Also, the numerical model was verified by animal tests. It improved the efficiency of design and reduce the demand for animal sacrifice.

Peripheral nerve injury is a life-changing disability with significant socioeconomic consequences. In this rat model, we propose that partial enzyme digestion can facilitate the functional recovery of a crushed nerve. The sciatic nerves were harvested and in vitro cultured with the addition of Liberase to determine the appropriate enzyme amount in the hyaluronic acid (HA) membrane. Then, the sciatic nerve of adult male Sprague-Dawley rats was exposed, crushed, and then treated with partial enzyme digestion (either 0.001 or 0.002 unit/mm2 Liberase-HA membrane). The sciatic function index (SFI) for functional recovery of the sciatic nerve was evaluated. After 2 h of in vitro digestion, fascicles and axons were separated from each other, with the cells mobilized. Greater destruction of histology structures occurred in the high enzyme (Liberase-HA membrane at 0.002 unit/mm2) group at 24 h than in the low enzyme (0.001 unit/mm2) group at 48 h. In the SFI evaluation, the improvement in 0.001 unit/mm2 Liberase group was significantly better than control and 0.002 unit/mm2 Liberase group. Our study demonstrated that appropriate enzyme digestion had a significantly faster and earlier recovery.

Mechanical stimuli are essential for the maintenance of tendon tissue homeostasis. The study aims to elucidate the mechanobiological mechanisms underlying the maintenance of tenocyte homeostasis by cyclic mechanical stretch under high-glucose (HG) condition.Primary tenocytes were isolated from rat Achilles tendon and 2D-cultured under HG condition. TheMechanical stretch increased tenocyte proliferation and upregulated early growth response protein 1 (Egr1) expression. An increase in intracellular calcium was observed after 30 min of stretching. Mechanical stretch phosphorylated FAK, calmodulin-dependent protein kinase kinase 2 (CaMKK2), and 5' adenosine monophosphate-activated protein kinase (AMPK) in a time-dependent manner, and these effects were abrogated after blocking intracellular calcium. Inhibition of FAK, CaMKK2, and AMPK downregulated the expression of Egr1. In addition, mechanical stretch reinforced cytoskeletal organization via calcium (Ca2+)/FAK signaling.Our study demonstrated that mechanical stretch-induced calcium influx activated CaMKK2/AMPK signaling and FAK-cytoskeleton reorganization, thereby promoting the expression of Egr1, which may help maintain tendon cell characteristics and homeostasis in the context of diabetic tendinopathy.

Current rat alveolar ridge preservation models have not been well standardized. In this study, we proposed decoronation-induced infected alveolar socket model of rat. The bilateral maxillary first molars (M1) of twenty-four rats were decoronized or extracted. After 2, 6, 10, and 14 weeks, bone and soft tissue changes at M1 and periodontal conditions of maxillary second (M2) and third molars (M3) were evaluated by micro-computed tomography and histological analysis. Additional eighteen rats with standardized size defects were grafted with Bio-Oss Collagen to compare with unmanipulated contralateral side. Decoronation preserved greater bone and soft tissue dimensions at M1, provided larger three-dimensional (3D) bone contour volume, but also promoted periodontal breakdown of M2 Histological results showed intense inflammatory cell infiltrations and severe bone resorption within M1 socket and at mesial aspect of M2. The critical dimensions to accommodate largest standardized defect at M1 were 2.2–2.3 mm at vertical bone height and 2.8–3.2 mm at alveolar crestal width. Bio-Oss Collagen could not fully preserve buccal or palatal bone height but could be beneficial in preserving ridge width in large alveolar defects. Collectively, if periodontally-involved alveolar bone defect is preferred, we suggest extracting M1 roots 6 weeks after decoronation to allow periodontitis to occur at M2. If standardized critical dimension defect is preferred, we suggest extracting M1 roots 2 weeks after decoronation, and creating defect in the middle of M1 site with size no larger than 2.7 mm diameter to its full depth.

Long term success of metallic fusion cages depends on mechanobiological processes through the bone incorporation and rich osseointegration. An optimal configuration of porous titanium-aluminum-vanadium (Ti 6Al 4V) implant fabricated via the additive manufacturing was evaluated in complimentary structure examinations to investigate the growth of autologous osseous at multi-length scales. X-ray microcomputed tomography (micro-CT) and transmission X-ray microscopy (TXM) using newly-built analysis method indicate the porous Ti 6Al 4V is much better for bone ingrowth compared to commercially non-porous titanium (Ti) and porous tantalum (Ta) implants at the ultramicrostructural level. The evolution of bone formation and remodeling acquired by nano X-ray Laue diffraction mapping exhibits the isotropic orientation and low crystallinity of all newly formed bone whereas mature bone in Ti 6Al 4V discloses the preferential alignment and higher crystallinity volumes of constituent hydroxyapatite (HA) crystallites. The high degree in mineral crystallinity of the fully mature bone suggests additive manufactured Ti 6Al 4V pores enhance the collagen-regulated mineralization.

BACKGROUND/PURPOSE Crestal bone stability, implant rigidity and occlusal loading are issues with small-diameter implants. This article demonstrates the use of two small-diameter implants replacing a missing wide edentulous site and discusses factors that may affect bone changes. METHODS Patients who wanted to restore an edentulous space measuring from 12 to 14 mm wide in the posterior region were offered an alternative treatment option, using two narrow or regular-diameter implants instead of one wide implant. In the study, the crestal bone stability of 12 implants in 6 edentulous sites was assessed by cone beam CTs and periapical radiographs in follow-up visits for up to 4 years. RESULTS The bone level of all the implants was stable at buccal, lingual, mesial and distal sites, with mean values

Although a range of pharmacological interventions is available, it remains uncertain which treatment for osteoporosis is more effective. This network meta-analysis study aimed to compare different drug efficacy and safety in randomized controlled trials (RCTs) for the treatment of postmenopausal osteoporosis. PubMed, EMBASE, MEDLINE, Clinicaltrial.gov, Cochrane library, Google scholar were searched up to 31 October 2020. Randomized placebo-controlled trials that reported measures of bone mineral density (BMD) percentage change and/or numbers of adverse events of postmenopausal osteoporosis patients were included. Network meta-analysis was conducted using frequentist approach. Ninety-four RCTs comprising 15,776 postmenopausal osteoporosis females were included in the network meta-analysis. Compared with placebo, most interventions showed increase in BMD change. According to surfaces under the cumulative ranking curves (SUCRAs), strontium ranelate, fluoride, and hormone replacement therapy were most effective in increasing total hip, lumbar spine, and distal radius BMD, respectively. Parathyroid hormone (PTH) was most effective in preventing new hip fracture. When taking into account all anatomic sites, bisphosphonate (BP), monoclonal antibody (mAb), and fluoride have a balanced efficacy in increasing BMD at all sites. Considering both the effectiveness of increasing BMD and preventing hip fracture, mAb, BP, and PTH are more favorable among all interventions. The treatment effects of different medications on BMD percentage change are anatomic site-dependent. After weighing anti-osteoporosis treatment efficacy against risk of complications, BP and mAb are the more favorable interventions to increase BMD at all sites and reduce the risks of hip fracture and death.

Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern healthcare of the aging and diseased population. In this study, we developed a novel nano-fibrous scaffold and verified its application in the critical bone defect regeneration. The metformin-incorporated nano-gelatin/hydroxyapatite fibers (NGF) was produced by electrospinning, cross-linked, and then characterized by XRD and FTIR. Cytotoxicity, cells adhesion, cell differentiation, and quantitative osteogenic gene and protein expression were analyzed by bone marrow stem cells from rat. Rat forearm critical bone defect model was performed for the in vivo study. The nano-gelatin/hydroxyapatite fibers (NGF) were characterized by their porous structures with proper interconnectivity without significant cytotoxic effects; the adhesion of bone marrow stem cells on the nano-gelatin/hydroxyapatite fibers (NGF) could be enhanced. The osteogenic gene and protein expression were upregulated. Post implantation, the new regenerated bone in bone defect was well demonstrated in the NGF samples. We demonstrated that the metformin-incorporated nano-gelatin-hydroxyapatite fibers greatly improved healing potential on the critical sized bone defect. Although metformin-incorporated nano-gelatin/hydroxyapatite fibers had advantageous effectiveness during bone regeneration, further validation is required before it can be applied to clinical applications.

Implant-related infection may be catastrophic and result in poor functional outcome, chronic osteomyelitis, implant failure or even sepsis and death. Based on a transglutaminase (TGase) cross-linked/antibiotics-encapsulated gelatin-alginate hydrogel, the main aim of this study is to establish an effective antibiotic slow-release system. The second aim is to evaluate the efficacy of a hydrogel-encapsulated antibiotic-containing titanium pin in preventing implant-related infections in a rat model. The prepared gelatin/alginate/gentamicin or vancomycin hydrogel was covalently cross-linked with transglutaminase (TGase). Its drug release profile and cytotoxicity were determined and the Wistar rat animal model was performed to validate its efficacy by radiographic examination, Micro-CT (computed tomography) evaluation and histo-morphological analysis at 12 weeks after surgery. When gelatin and alginate were thoroughly mixed with TGase, both 0.5% and 1.0% TGase can effectively cross link the hydrogel, the release of antibiotic is slowed down with higher degree of TGase concentration (from 20 min to more than 120 h). In the animal study, antibiotic-impregnated hydrogel is effective in alleviating the implant-related infections. Relative to that of a positive control group, the experimental group (vancomycin treatment group) showed significant higher bone volume, more intact bony structure with only mild inflammatory cell infiltration. This newly designed hydrogel can effectively deliver antibiotics to reduce bacterial colonization and biofilm formation on the implant surface. The remaining challenges will be to confer different potent antibacterial medications with good biocompatibility and fulfill the safety, practical and economic criteria for future clinical translation.

There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.

The interference screw is a widely used fixation device in the anterior cruciate ligament (ACL) reconstruction surgeries. Despite the generally satisfactory results, problems of using interference screws were reported. By using additive manufacturing (AM) technology, we developed an innovative titanium alloy (Ti6 Al4 V) interference screw with rough surface and inter-connected porous structure designs to improve the bone-tendon fixation. An innovative Ti6 Al4 V interference screws were manufactured by AM technology. In vitro mechanical tests were performed to validate its mechanical properties. Twenty-seven New Zealand white rabbits were randomly divided into control and AM screw groups for biomechanical analyses and histological analysis at 4, 8, and 12 weeks postoperatively; while micro-CT analysis was performed at 12 weeks postoperatively. The biomechanical tests showed that the ultimate failure load in the AM interference screw group was significantly higher than that in the control group at all tested periods. These results were also compatible with the findings of micro-CT and histological analyses. In micro-CT analysis, the bone-screw gap was larger in the control group; while for the additive manufactured screw, the screw and bone growth was in close contact. In histological study, the bone-screw gaps were wider in the control group and were almost invisible in the AM screw group. The innovative AM interference screws with surface roughness and inter-connected porous architectures demonstrated better bone-tendon-implant integration, and resulted in stronger biomechanical characteristics when compared to traditional screws. These advantages can be transferred to future interference screw designs to improve their clinical performance. The AM interference screw could improve graft fixation and eventually result in better biomechanical performance of the bone-tendon-screw construct. The innovative AM interference screws can be transferred to future interference screw designs to improve the performance of implants. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2633-2640, 2018.

Background: Various surgical techniques are available to reduce chronic instability of the lateral ankle ligament complex. The most effective method for these procedures remains controversial. This report presents a surgical technique that is similar to the Broström procedure and uses a modified, nonaugmented repair technique. Materials and Methods: 38 soldiers with a history of chronic lateral ankle instability and poor ankle function underwent plication of the anterior talofibular ligament-lateral capsule complex with transosseous fixation of the calcaneofibular ligament through a fibular bone tunnel between 2004 and 2007. This study included 33 men and 5 women with a mean age of 25.6 years (range 18–36 years) at the time of surgery. Each patient was confirmed to have a history of chronic lateral ankle instability after an inversion injury, and symptoms had been noted for at least 1 year. The patients were followed up with stress radiographs, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot functional score, and the Sefton assessment system. The mean followup period was 77.6 months (range 66-89 months). Results: At the last evaluation, the talar tilt reduced from an average of 13.9° ± 2.4° before surgery to 3.8° ± 1.8° after surgery, and anterior drawer displacement reduced from 9.6 ± 2.9 mm to 2.3 ± 1.6 mm. The mean AOFAS ankle-hindfoot scale score for functional stability increased from 71.6 ± 4.0 points preoperatively to 95.6 ± 4.0 points postoperatively. As evaluated by the Sefton assessment system, 36 patients (95%) reported an excellent or good functional outcome. All patients resumed normal daily activities and active military duty after the surgery. Conclusion: The procedure described here could be considered a viable alternative option to anatomic reconstruction such as the modified Broström procedure and might be appropriate for the general population.

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.

Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth. The gelatin-based conduits mimicked the fascicular architecture of natural nerve ECM. The multichanneled (MC) scaffolds, cross-linked with microbial transglutaminase, possessed sustainable mechanical stability. Meanwhile, the release profile of dual neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), exhibited a temporal-controlled manner. In vitro, the differentiated neural stem cells effectively extended their neurites along the aligned nanofibers. Besides, in the treated group, the cell density increased in high NGF concentration regions of the gradient membrane, and the BDNF significantly promoted myelination. In a rabbit sciatic nerve transection in vivo model, the MC/AN/NG scaffold showed superior nerve recovery and less muscle atrophy comparable to autograft. By integrating multiple strategies to promote peripheral nerve regeneration, the MC/AN/NG scaffolds as nerve guidance conduits showed promising results and efficacious treatment alternatives for autologous nerve grafts.

Several plate systems for high tibial osteotomy (HTO) have been developed to stabilize the opening wedge of an osteotomized tibia. Among them, the TomoFix system, having a quasi-straight and T-shaped design, has been widely adopted in the literature. However, this system is implemented by inserting a lag (i.e., cortical) screw through the proximal combi-hole, to deform the plate and pull the distal tibia toward the plate. This process potentially induces plate springback and creates an elastic preload on the osteotomized tibia, especially at the lateral hinge of the distracted wedge. Using the finite-element method, this study aims to investigate the contoured effect of lag-screw application on the biomechanical behavior of the tibia-plate construct. Two tibial profiles (normal and more concave), three distraction angles (6°, 9°, and 12°), and three knee loads (intraoperative: contouring plate; postoperative: weight and nonweight bearing) are systematically varied in this study. The wedge instability and fracture risk at the lateral hinge are chosen as the comparison indices. The results show the necessity of preoperative planning for a precontoured procedure, rather than elastic deformation using a lag screw. Within the intraoperative period, a more concave tibial profile and/or reduced distraction angle (i.e., 6° or 9°) necessitate a higher compressive load to elastically deform the plate, thereby deteriorating the lateral-hinge fracture risk. A precontoured plate is recommended in the case that the proximal tibia is highly concave and the distraction angle is insufficient to stretch the tibial profile.

Skeletal muscle is the biological tissue able to transform chemical energy to mechanical energy. Skeletal muscle has three basic performance parameters that describe its function: structure and composition, force production, and movement production. From a mechanical perspective, the musculotendinous unit behaves as an elastic-contractile component (muscle fibers) in series with another elastic component (tendons) to move human body. Due to their unique hierarchical structure and composition, tendons possess characteristic biomechanical properties, including high mechanical strength and viscoelasticity, which enable them to carry and transmit mechanical loads (muscular forces) effectively. Tendons are also mechano-responsive by adaptively changing their structure and function in response to altered mechanical loading conditions. The production of movement and force is the mechanical outcome of skeletal muscle contraction. The focus of this chapter is on the biomechanical behavior of skeletal muscle and tendon as they contribute to function of the musculoskeletal system.

The development of a novel alloplastic graft with both osteoinductive and osteoconductive properties is still necessary. In this study, we tried to synthesize a biomimetic hydroxyapatite microspheres (gelatin/nano-hydroxyapatite microsphere embedded with stromal cell-derived factor-1: GHM-S) from nanocrystalline hydroxyapatites and to investigate their therapeutic potential and effects on bone regeneration. In this study, hydroxyapatite was synthesized by co-precipitation of calcium hydroxide and orthophosphoric acid to gelatin solution. The microbial transglutaminase was used as the agent to crosslink the microspheres. The morphology, characterization, and thermal gravimetric analysis of microspheres were performed. SDF-1 release profile and in vitro biocompatibility and relative osteogenic gene expression were analyzed, followed by in vivo micro-computed tomography study and histological analysis. The synthesized hydroxyapatite was found to be similar to hydroxyapatite of natural bone tissue. The stromal cell-derived factor-1 was embedded into gelatin/hydroxyapatite microsphere to form the biomimetic hydroxyapatite microsphere. The stromal cell-derived factor-1 protein could be released in a controlled manner from the biomimetic hydroxyapatite microsphere and form a concentration gradient in the culture environment to attract the migration of stem cells. Gene expression and protein expression indicated that stem cells could differentiate or develop into pre-osteoblasts. The effect of bone formation by the biomimetic hydroxyapatite microsphere was assessed by an in vivo rats&rsquo, alveolar bone defects model and confirmed by micro-CT imaging and histological examination. Our findings demonstrated that the biomimetic hydroxyapatite microsphere can enhance the alveolar bone regeneration. This design has potential be applied to other bone defects.

Alveolar bone loss following peri-implantitis remains a clinical challenge. We aimed to design a novel bioactive dental implant to accommodate the large bone defect caused by removal of previously failed implant.Bio-ActiveIn histomorphometrical evaluation and micro-CT analysis, active new bone formation and good osseointegration within the ITRI implants were observed at the bone gap surrounding the dental implants. The biomechanical parameters in the Bio-ActiveThe novel porous structured Bio-Active

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.

Background Polymethylmethacrylate bone cement has a variety of applications in orthopedic surgery, but it also has some shortcomings such as high heat generation during polymerization and poor integration with bone tissue. In this study, a bio-composite bone cement composed of tri-calcium phosphate and chitosan as additives to acrylic bone cement was developed. Our hypothesis is that this new bio-composite bone cement has a better osteo-integration than pure polymethyl methacrylate cement. Methods Physiological composition, i.e., 65 wt% inorganic and 35 wt% organic components, of tri-calcium phosphate and chitosan contents was selected as degradable additives to replace acrylic bone cement. A series of properties such as exothermic temperature changes, setting time, bio-mechanical characteristics, degradation behaviors, and in vitro cytotoxicity were examined. Preliminary in vivo animal study was also performed. Results The results showed that the bio-composite bone cement exhibited lower curing temperature, longer setting time, higher weight loss and porosity after degradation, lower compressive Young’s modulus, and ultimate compressive strength as compared with those of pure polymethyl methacrylate cement. Cell proliferation tests demonstrated that the bio-composite bone cement was non-cytotoxic, and the in vivo tests revealed that was more osteo-conductive. Conclusions The results indicated that the modified chitosan/tri-calcium phosphate/polymethyl methacrylate bio-composites bone cement could be degraded gradually and create rougher surfaces that would be beneficial to cell adherence and growth. This new bio-composite bone cement has potential in clinical application. Our future studies will focus on long-term implantation to investigate the stability of the bio-composite bone cement in long-term implantation.

With the goal to explore a new approach to treat the early degenerative lesions of hyaline cartilage, we implanted in a porcine OA model a collagen-based scaffold containing chondroprogenitor cells derived from human bone marrow mesenchymal stem cells (hBM-MSCs).Porcine knee joints were subjected to anterior cruciate ligament (ACL) transection to surgically induce OA. After 4 months, the time necessary for the development of cartilage surface damage, animals were treated either with trephination bone plug wrapped with the chondroprogenic hBM-MSCs-embedded collagen scaffold or microfractures alone. Histological and histomorphometric evaluations were performed at 5 months after surgery.All animals subjected to ACL transection showed osteoarthritic changes including mild lateral femoral condyle or moderate medial femoral condyle ulcerations. After 14 days' chondrogenic induction, hBM-MSCs seeded onto the scaffold showed expression of chondroprogenitor markers such as SOX9 and COMP. At 5 months after the implantation, significant differences in the quality of the regenerated tissue were found between the hBM-MSCs-embedded scaffold group and the control group. Newly generated tissue was only observed at the site of implantation with the hBM-MSCs-embedded scaffolds. Furthermore, histological examination of the generated tissue revealed evidence of cartilage-like tissue with lacuna formation. In contrast, fibrous layers or fissures were formed on the surface of the control knee joint.This study shows that xenogenic hBM-MSC derived chondroprogenitor scaffolds can generate new cartilage tissue in porcine articular cartilage and have the potential as a useful treatment option for osteoarthritis.

The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D 1H NMR spectroscopy. In vitro analysis showed that the ibuprofen-conjugated polygalacturonic acid–hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E2 production of the lipopolysaccharide-induced RAW264.7 cells. Histological data in in vivo studies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofen via a polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis.

Background The management of complaints in the setting of intensive care may provide opportunities to understand patient and family experiences and needs. However, there are limited reports on the structured application of complaint analysis tools and comparisons between healthcare complaints in the critical care setting and other settings. Methods From the complaint management database of a university-affiliated medical center in Taiwan, we retrospectively identified the records of healthcare complaints to the intensive care units (ICUs) from 2008 to 2016. Complaints to the general wards in the same period were randomly selected from the database with twice the number of that of the ICU complaints. We coded, typed, and compared the complaints from the two settings according to the Healthcare Complaint Analysis Tool. Results We identified 343 complaints to the ICUs and randomly selected 686 complaints to the general wards during the 9-year study period. Most (94.7%) of the complaints to the ICUs came from the family members, whereas more complaints to the general wards came from the patients (44.2%). A total of 1529 problems (441 from ICU and 818 from general wards) were identified. Compared with the general ward complaints, in the ICU there were more complaints with multiple problems (25.1% vs. 16.9%, p = 0.002), complaints were referred more frequently to the nurses (28.1% vs. 17.5%, p

The poor regenerative capability of stem cell transplantation in the central nervous system limits their therapeutic efficacy in brain injuries. The sustained inflammatory response , lack of structural support, and trophic factors deficiency restrain the integration and long-term survival of stem cells. Instead of exogenous stem cell therapy, here we described the synthesis of nanohybrid hydrogel containing sulfated glycosaminoglycan-based polyelectrolyte complex nanoparticles (PCN) to mimic the brain extracellular matrix and control the delivery of stromal-derived factor-1α (SDF-1α) and basic fibroblast factor (bFGF) in response to matrix metalloproteinase (MMP) for recruiting endogenous neural stem cells (NSC) and regulating their cellular fate. Bioactive factors are delivered by electrostatic sequestration on PCN to amplify the signaling of SDF-1α and bFGF to regulate NSC in vitro . In in vivo ischemic stroke model, the factors promoted neurological behavior recovery by enhancing neurogenesis and angiogenesis . These combined strategies may be applied for other tissue regenerations by regulating endogenous progenitors through the delivery of different kinds of glycosaminoglycan-binding molecules.