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Background: Regenerative techniques are increasingly being advocated in endodontic apical surgery (AS) to enhance the healing of periapical lesions. Various grafting and membrane materials are employed as adjuncts to modern AS. Objectives: This systematic review aimed to answer the following PICO question: In patients with apical periodontitis (P) what is the impact of bone grafting with/without barrier membrane materials (I) compared with surgery without grafting materials (C) on the outcome of AS evaluated clinically and radiographically (O). Methods: A systematic search was conducted in four databases (Embase, Web of Science, PubMed and Cochrane Central Register of Controlled Trials) until 1 August 2023. Google Scholar was also manually searched. Studies with a prospective randomized design were included. Cochrane risk‐of‐bias (RoB) tool 2.0 assessed bias. Two independent reviewers performed the study selection, data extraction and appraisal of studies. Meta‐analysis was performed using R3.5.1 software. Results: From the identified 2582 studies, eight randomized clinical trials were included for meta‐analysis. Two studies had low RoB, while six had some concerns. Analysis revealed significantly better outcomes when surgery involved bone regeneration techniques than conventional surgery (OR = 2.18, 95% CI: 1.32–4.31, p =.004). Subgroup analyses on individual grafts (OR = 0.22, 95% CI: −0.99 to 1.44, p =.720) (OR = −0.09, 95% CI: −1.42 to 1.23, p =.885) and membranes (OR = −1.09, 95% CI: −2.94 to 0.76, p =.247) and their combinations (OR = 0.03, 95% CI: −1.50 to 1.55, p =.970) did not yield any significant results. The type of membrane used did not significantly impact the outcome (OR = −1.09, 95% CI: −2.94 to 0.76, p =.247) nor did altering the combination of graft/membrane. Discussion: This systematic review examined the effects of bone grafting with/without membrane placement on the outcome of AS. It highlights the potential advantages of regenerative techniques and the need for further research in this area. Conclusions: Based on current evidence, bone grafting with/without barrier membrane placement significantly improves healing after AS. Subgroup analysis of resorbable membranes or grafting did not significantly influence the outcome. The combination of membrane and graft was also not significant. Future well‐designed, randomized controlled trials in this area are essential before these materials can be recommended for routine use to enhance healing outcomes in AS. Registration: PROSPERO (CRD42021255171). [ABSTRACT FROM AUTHOR]

Background/purpose: In the field of conservative dentistry and endodontics, mineral trioxide aggregate (MTA), commonly used, possesses advantages such as biocompatibility, antimicrobial properties and osteogenic potential. This study investigated the feasibility of utilizing membrane form mineral trioxide aggregate (MTA) as a barrier membrane in guided bone regeneration (GBR) procedures. Materials and methods: Membranes were electrospun from three different formulations: 15 w/v% Polycaprolactone (PCL), 13 w/v% PCL + 2 w/v% MTA (2MTA), and 11 w/v% PCL + 4 w/v% MTA (4MTA). Physicochemical and mechanical properties of the electrospun membrane were compared, encompassing parameters such as surface morphology, fiber diameter distribution, chemical composition, phase identification, tensile stress, pH variation, and water contact angle. Moreover, the antimicrobial properties against of the electrospun membranes were assessed through direct exposure to streptococcus aureus (S. aureus) and candida albicans (C. albicans). Additionally, on the 7th day, biocompatibility and cell attachment were investigated with respect to L929 (fibroblast) and MC3T3 (pre-osteoblast) cells. Inhibition of L929 cell infiltration and the expression of osteogenic related genes including osteocalcin (OCN), alkaline phosphatase (ALP), and runt related transcription factor 2 (RUNX2) in MC3T3 cells on 7th and 14th days were also investigated. Results: PCL, 2MTA, and 4MTA exhibited no statistically differences in fiber diameter distribution and tensile stress. However, as the MTA content increased, wettability and pH also increased. Due to the elevated pH, 4MTA demonstrated the lowest viability S.aureus and C.albicans. All membranes were highly biocompatibility and promoted cell attachment, while effectively preventing L929 cell infiltration. Lastly 4MTA showed increase in OCN, ALP, and RUNX2 expression on both 7th and 14th day. Conclusion: The membrane form MTA possessed characteristics essential for a novel barrier membrane.

In the field of conservative dentistry and endodontics, mineral trioxide aggregate (MTA), commonly used, possesses advantages such as biocompatibility, antimicrobial properties and osteogenic potential. This study investigated the feasibility of utilizing membrane form mineral trioxide aggregate (MTA) as a barrier membrane in guided bone regeneration (GBR) procedures. Membranes were electrospun from three different formulations: 15 w/v% Polycaprolactone (PCL), 13 w/v% PCL + 2 w/v% MTA (2MTA), and 11 w/v% PCL + 4 w/v% MTA (4MTA). Physicochemical and mechanical properties of the electrospun membrane were compared, encompassing parameters such as surface morphology, fiber diameter distribution, chemical composition, phase identification, tensile stress, pH variation, and water contact angle. Moreover, the antimicrobial properties against of the electrospun membranes were assessed through direct exposure to streptococcus aureus (S. aureus) and candida albicans (C. albicans). Additionally, on the 7th day, biocompatibility and cell attachment were investigated with respect to L929 (fibroblast) and MC3T3 (pre-osteoblast) cells. Inhibition of L929 cell infiltration and the expression of osteogenic related genes including osteocalcin (OCN), alkaline phosphatase (ALP), and runt related transcription factor 2 (RUNX2) in MC3T3 cells on 7th and 14th days were also investigated. PCL, 2MTA, and 4MTA exhibited no statistically differences in fiber diameter distribution and tensile stress. However, as the MTA content increased, wettability and pH also increased. Due to the elevated pH, 4MTA demonstrated the lowest viability S.aureus and C.albicans. All membranes were highly biocompatibility and promoted cell attachment, while effectively preventing L929 cell infiltration. Lastly 4MTA showed increase in OCN, ALP, and RUNX2 expression on both 7th and 14th day. The membrane form MTA possessed characteristics essential for a novel barrier membrane. [ABSTRACT FROM AUTHOR]

The guided tissue regeneration (GTR) procedure has become an important process for the treatment of periodontal tissue regeneration, using the membrane as a mechanical barrier to generate a distance across the defect that subsequently allowing bone regeneration. Due to the complexity of periodontal microenvironment caused by bacterial infections, inflammation, and fibrous tissue penetration, the guided tissue regeneration membrane is required to have antibacterial and barrier functions. We developed a loaded methylene blue @ ZIF-8 and hydroxyapatite gradient thermoplastic polyurethane Janus membrane for antibacterial osteogenic and barrier. This Janus membrane with a porous gradient structure was prepared to use phase-conversion method. The rough layer facilitated cell growth and promoted periodontal bone regeneration, whereas the smooth layer isolated the growing fiber tissue.The rapid release of reactive oxygen species in the early stage and continuous release of zinc ions by methylene blue @ZIF-8 can achieve long-term synergistic antibacterial effect, with antibacterial rates of 84 % and 72 % against Escherichia coli and Staphylococcus aureus, respectively, which can effectively reduce the local inflammation caused by bacteria. In summary, we applied the Janus membrane to a rat periodontal bone defect model, and the membrane showed good surgical performance, barrier properties, osteogenic properties, and antibacterial effects, which could have broad application prospects in the treatment of periodontal bone defects.

Background/purpose: Porcine collagen is widely used in regenerative therapies to generate membranes for bone augmentation. However, porcine or bovine gelatin or collagen is often not appropriate for patients with creed and religious beliefs or for allergic reasons. In this study, we evaluated the potential of fish gelatin to generate membranes. Materials and methods: Fish gelatin and hydroxyapatite (HAp) were used at three different ratios (2:0, 2:1, 2:1.5, and 2:2) to prepare gelatin-hydroxyapatite (G-HAp) membranes via freeze-drying and heat-crosslinking. The surface morphology and cell attachment of G-HAp membranes were observed using scanning electron microscopy and confocal laser microscopy. G-HAp membrane was placed at the bottom of a well plate, and MC3T3-E1 cells were seeded on it. Cell viability and cytotoxicity were tested after 1 and 3 days of culture. Alkaline phosphatase (ALP) and alizarin red staining was performed at 10 and 21 days, respectively. Results: Viability of cells on G-HAp membrane with the gelatin:HAp ratio of 2:1.5 was significantly higher than that on membranes with other gelatin:HAp ratios. ALP and alizarin red staining showed that ALP-positive areas and calcium deposition were the highest on G-HAp membrane with the gelatin:HAp ratio of 2:1. These membranes showed negligible cytotoxicity. Conclusion: Fish-derived G-HAp membranes have the potential to promote osteogenic differentiation of MC3T3-E1 cells with negligible cytotoxicity.

Porcine collagen is widely used in regenerative therapies to generate membranes for bone augmentation. However, porcine or bovine gelatin or collagen is often not appropriate for patients with creed and religious beliefs or for allergic reasons. In this study, we evaluated the potential of fish gelatin to generate membranes. Fish gelatin and hydroxyapatite (HAp) were used at three different ratios (2:0, 2:1, 2:1.5, and 2:2) to prepare gelatin-hydroxyapatite (G-HAp) membranes via freeze-drying and heat-crosslinking. The surface morphology and cell attachment of G-HAp membranes were observed using scanning electron microscopy and confocal laser microscopy. G-HAp membrane was placed at the bottom of a well plate, and MC3T3-E1 cells were seeded on it. Cell viability and cytotoxicity were tested after 1 and 3 days of culture. Alkaline phosphatase (ALP) and alizarin red staining was performed at 10 and 21 days, respectively. Viability of cells on G-HAp membrane with the gelatin:HAp ratio of 2:1.5 was significantly higher than that on membranes with other gelatin:HAp ratios. ALP and alizarin red staining showed that ALP-positive areas and calcium deposition were the highest on G-HAp membrane with the gelatin:HAp ratio of 2:1. These membranes showed negligible cytotoxicity. Fish-derived G-HAp membranes have the potential to promote osteogenic differentiation of MC3T3-E1 cells with negligible cytotoxicity. [ABSTRACT FROM AUTHOR]

This case report provides a detailed description of a simple and fast bone regeneration procedure using a semi-customized three-dimensional ultra-fine titanium mesh. A 50-year-old male with a severe vertical and horizontal bone defect in the anterior mandible underwent implant treatment in a staged approach. The autologous bone was combined with a xenograft, and the mixture was grafted to augment the bone defect and covered with semi-customized ultra-fine titanium meshes, which were selected among its various types according to size and configuration of the bone defect, directly connected and immobilized on the tenting screws with minimal shaping. In a postoperative 6 months re-entry surgery, the performed titanium meshes were removed, implants were placed, and a bone core biopsy was obtained that demonstrated satisfactory new bone formation. Finally, two months later, the definitive prosthesis was installed. This semi-customized ultra-fine titanium mesh could help an implant clinician obtain more predictable results in the guided bone regeneration (GBR). [ABSTRACT FROM AUTHOR]

Background Methods and Results Conclusions Key points Current evidence acknowledges guided bone regeneration (GBR) as a predictable therapeutic modality in the augmentation of a deficient alveolar ridge. Such deficiencies often reveal inadequate bone volume to support implant placement in a position amenable to prosthetic reconstruction. Additionally, an evolving body of literature demonstrates that membrane fixation may lead to improved clinical bone gain through positively influencing blood clot formation, stability, and the eventual osteogenic potential of the defect. Alternative benefits to membrane fixation, such as reduced graft displacement and reduction in wound micromotion, have also been cited as mechanisms for an increased regenerative response.The aim of this report was to present a case, including diagnosis, treatment, and follow‐up for the reconstruction of a horizontal ridge deficiency. The patient's deficiency in ridge volume was found to be a developmental sequelae of lateral incisor agenesis, resulting in an underdeveloped midfacial region of the alveolar process subjacent to sites #7 and #10. The fixation protocol outlined in this report demonstrated adequate horizontal ridge augmentation to facilitate future prosthetic reconstruction with the use of implants.Numerous protocols have been established in an attempt to achieve effective barrier membrane stabilization for bone augmentation procedures. However, some techniques are poorly suited for the anatomically challenging region of the anterior maxilla. A case report describing the utilization of the anterior nasal spine for anchorage of a membrane‐stabilizing suture may present a novel, safe, and effective technique for stabilizing the intended region of augmentation, as well as preventing graft migration beyond the membrane–maxilla interface. Regarding guided bone regeneration (GBR) procedures, micromotion of the membrane or of the underlying particulate graft may negatively influence the volume of the augmented site. The ability to adequately stabilize the graft–membrane interface is recognized as a necessary prerequisite to predictably achieve optimal surgical outcomes. To the authors’ knowledge, there is no clinical or scientific evidence regarding the use of the anterior nasal spine for membrane anchorage in maxillary GBR procedures, and thus a novel approach to membrane stabilization is introduced. Regarding guided bone regeneration (GBR) procedures, micromotion of the membrane or of the underlying particulate graft may negatively influence the volume of the augmented site.The ability to adequately stabilize the graft–membrane interface is recognized as a necessary prerequisite to predictably achieve optimal surgical outcomes.To the authors’ knowledge, there is no clinical or scientific evidence regarding the use of the anterior nasal spine for membrane anchorage in maxillary GBR procedures, and thus a novel approach to membrane stabilization is introduced. [ABSTRACT FROM AUTHOR]

Both guided bone and guided tissue regeneration are techniques that require the use of barrier membranes. Contamination and infection of the surgical area is one of the most feared complications. Some current lines of research focus on functionalizing these membranes with different antimicrobial agents. The objective of this study was to carry out a review of the use and antibacterial properties of regeneration membranes doped with antimicrobials such as zinc, silver, chlorhexidine, and lauric acid. The protocol was based on PRISMA recommendations, addressing the PICO question: "Do membranes doped with non-antibiotic antimicrobials have antibacterial activity that can reduce or improve infection compared to membranes not impregnated with said antimicrobial?" Methodological quality was evaluated using the RoBDEMAT tool. A total of 329 articles were found, of which 25 met the eligibility criteria and were included in this review. Most studies agree that zinc inhibits bacterial growth as it decreases colony-forming units, depending on the concentration used and the bacterial species studied. Silver compounds also decreased the secretion of proinflammatory cytokines and presented less bacterial adhesion to the membrane. Some concentrations of chlorhexidine that possess antimicrobial activity have shown high toxicity. Finally, lauric acid shows inhibition of bacterial growth measured by the disk diffusion test, the inhibition zone being larger with higher concentrations. Antimicrobial agents such as zinc, silver, chlorhexidine, and lauric acid have effective antibacterial activity and can be used to dope regenerative membranes in order to reduce the risk of bacterial colonization. [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) is a treatment strategy used to recover bone volume. Barrier membranes are a key component of GBR protocols, and their properties can impact treatment outcomes. This study investigated the efficacy of an experimental, slow‐degrading, bilayer barrier membrane for application in GBR using in vivo animal models. A synthetic copolymer of poly(lactic acid/caprolactone) (PLCL) was used to prepare a slow‐degrading bilayer membrane. The biodegradability of PLCL was evaluated by subcutaneous implantation in a rat model. The barrier function of the PLCL membrane was investigated in a rat calvaria defect model and compared with commercially available membranes composed of type I collagen (Col) and poly(lactic‐co‐glycolic acid) (PLGA). An alveolar bone defect model in beagle dogs was used to simulate GBR protocols to evaluate the bone regeneration ability of the experimental PLCL membrane. The PLCL membrane showed slow biodegradation, resulting in an efficient and prolonged barrier function compared with commercial materials. In turn, this barrier function enabled the space‐making ability of PLCL membrane and facilitated bone regeneration. In the alveolar bone defect model, significantly greater regeneration was achieved by treatment with PLCL membrane compared with Col and PLGA membranes. Additionally, a continuous alveolar ridge contour was observed in PLCL‐treated bone defects. In conclusion, the PLCL bilayer membrane is a promising biomaterial for use in GBR given its slow degradation and prolonged barrier function. [ABSTRACT FROM AUTHOR]

Abstract Background To provide a reference for clinical selection of collagen membranes by analyzing the properties of three kinds of collagen membranes widely used in clinics: Bio-Gide membrane from porcine dermis (PD), Heal-All membrane from bovine dermis (BD), and Lyoplant membrane from bovine pericardium (BP). Methods The barrier function of three kinds of collagen membranes were evaluated by testing the surface morphology, mechanical properties, hydrophilicity, and degradation rate of collagen membranes in collagenase and artificial saliva. In addition, the bioactivity of each collagen membrane as well as the proliferation and osteogenesis of MC3T3-E1 cells were evaluated. Mass spectrometry was also used to analyze the degradation products. Results The BP membrane had the highest tensile strength and Young’s modulus as well as the largest water contact angle. The PD membrane exhibited the highest elongation at break, the smallest water contact angle, and the lowest degradation weight loss. The BD membrane had the highest degradation weight loss, the highest number of proteins in its degradation product, the strongest effect on the proliferation of MC3T3-E1 cells, and the highest expression level of osteogenic genes. Conclusions The PD membrane is the best choice for shaping and maintenance time, while the BD membrane is good for osteogenesis, and the BP membrane is suitable for spatial maintenance. To meet the clinical requirements of guided bone regeneration, using two different kinds of collagen membranes concurrently to exert their respective advantages is an option worth considering.

Bone augmentation procedures are frequent today in implant patients, since an implant should be circumferentially anchored in bone at completion of bone healing to have a good long‐term stability. The best documented surgical technique to achieve this goal is guided bone regeneration (GBR) utilizing barrier membranes in combination with bone fillers. This clinical review paper reflects 35 years of development and progress with GBR. In the 1990s, GBR was developed by defining the indications for GBR, examining various barrier membranes, bone grafts, and bone substitutes. Complications were identified and reduced by modifications of the surgical technique. Today, the selection criteria for various surgical approaches are much better understood, in particular, in post‐extraction implant placement. In the majority of patients, biodegradable collagen membranes are used, mainly for horizontal bone augmentation, whereas bioinert PTFE membranes are preferred for vertical ridge augmentation. The leading surgeons are using a composite graft with autogenous bone chips to accelerate bone formation, in combination with a low‐substitution bone filer to better maintain the augmented bone volume over time. In addition, major efforts have been made since the millenium change to reduce surgical trauma and patient morbidity as much as possible. At the end, some open questions related to GBR are discussed. [ABSTRACT FROM AUTHOR]

Maxillary sinus augmentation with a lateral approach (MSA) is a well-established treatment. In this prospective study, we evaluated risk factors for postoperative bone graft displacement and reported the clinical application of long-term resorbable L-lactic acid/-caprolactone (PLA/PCL) as a barrier membrane to cover the open window in the lateral wall in MSA. Twenty-four patients underwent MSA according to the relevant criteria; CT data obtained before and 1 week (1 w) and 5–6 months (5 m) post-MSA, bone height changes, bone height reduction rates at 1 w and 5 m post-MSA, bone graft displacement measurements, and risk factors were examined. All patients showed bone height increments (p < 0.005). However, no difference was observed between 1 w and 5 m post-MSA. Bone graft displacement was observed in eight patients; the reduction rate from 1 w to 5 m post-MSA was 8.38% ± 4.88%. Sex, septa, maxillary sinus floor–palatal bone distance, and maxillary sinus floor–maxillary ostium distance were associated with bone graft displacement (p < 0.05). The height from the maxillary sinus floor to the palatal bone and the sinus angle influenced the augmentation degree (p < 0.05). The PLA/PCL membrane is compared favorably with other membranes and may be useful as a barrier membrane for the MSA open window. [ABSTRACT FROM AUTHOR]

The development of barrier membranes with non-mammalian fish collagen material for Guided Bone Regeneration (GBR) in the treatment of alveolar bone defects due to periodontitis, has the advantage of low risk of infectious disease transmission in tissue regeneration. This study aimed to produce and characterize a barrier membrane derived from carp scale collagen material. This study conducted the manufacture of collagen membranes with formula 1 consisting of 3% carp scale collagen, 2% chitosan and 7.5% polyvinyl alcohol (PVA), and formula 2 consisting of 3% carp scale collagen and 7.5% PVA by solution mixing and film printing. Membrane characterization with water absorption test, mechanical test, SEM and EDS characterization, and Fourier transform infrared (FTIR) spectroscopy test. This study found a significant difference in water absorption between the two membranes; the elastic modulus, tensile strength and breaking strain of membrane formula 1 are 0.38 Mpa, 7.82 N/mm2 and 2.51%, smaller than membrane formula 2 which are 1.00058 Mpa, 21.95 N/mm2 and 23.69%; SEM image of membrane formula 1 shows surface porous and bonding between elements is better than formula 2; EDS results and map sum spectrum of membrane formula 1 showed detected elements of C (59%), O (40%), Ca (0.6%), and Si, Al and Mg, while formula 2 detected elements of C (59.7%), O (40.1%), and Si and Ca; FTIR spectra showed that both membranes have tri helical functional groups as a requirement for barrier membranes. Periodontal regenerative surgery barrier membrane based on carp scale collagen can be effectively produced with desired properties. [ABSTRACT FROM AUTHOR]

Poly(L-lactic acid) (PLLA) and PLLA/gelatin polymers were prepared via electrospinning to evaluate the effect of PLLA and gelatin content on the mechanical properties, water uptake capacity (WUC), water contact angle (WCA), degradation rate, cytotoxicity and cell proliferation of membranes. As the PLLA concentration increased from 1 wt% to 3 wt%, the tensile strength increased from 5.8 MPa to 9.1 MPa but decreased to 7.0 MPa with 4 wt% PLLA doping. The WUC decreased rapidly from 594% to 236% as the PLLA content increased from 1 to 4 wt% due to the increased hydrophobicity of PLLA. As the gelatin content was increased to 3 wt% PLLA, the strength, WUC and WCA of the PLLA/gelatin membrane changed from 9.1 ± 0.9 MPa to 13.3 ± 2.3 MPa, from 329% to 1248% and from 127 ± 1.2° to 0°, respectively, with increasing gelatin content from 0 to 40 wt%. However, the failure strain decreased from 3.0 to 0.5. The biodegradability of the PLLA/gelatin blend increased from 3 to 38% as the gelatin content increased to 40 wt%. The viability of L-929 and MG-63 cells in the PLLA/gelatin blend was over 95%, and the excellent cell proliferation and mechanical properties suggested that the tunable PLLA/gelatin barrier membrane was well suited for absorbable periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

Abstract Guided bone regeneration (GBR) is widely used in treating oral bone defects to exclude the influence of non-osteogenic tissue on the bone healing process. The traditional method of GBR with a titanium mesh to treat large-area bone defects is limited by the deficiency of increased trauma and costs to patients. Herein, a bi-layered scaffold for GBR composed of a fiber barrier layer and a self-healing hydrogel repair layer is successfully fabricated. The barrier layer is a fibrous membrane material with specific porosity constructed by electrospinning, while the functional layer is a self-healing hydrogel material formed by multiple dynamic covalent bonds. The system can provide an osteogenic microenvironment by preventing the infiltration of connective tissue to bone defects, maintain the stability of the osteogenic space through the self-healing property, and regulate the release of bioactive substances in the dynamic physical condition, which is beneficial to osteoblast proliferation, differentiation, and bone regeneration. This study focused on exploring the effects of different crosslinkers and bonding methods on the comprehensive properties of hydrogels. and proved that the hybrid scaffold system has good biocompatibility, cell barrier function and can enhance bone regeneration activity. Thereby it could be a promising clinical strategy for bone regeneration.

Purpose: A barrier membrane consisting of an equine-derived, demineralized cortical bone sheet has been made available, yet evidence of its effectiveness is currently only anecdotal. This study aimed to obtain preliminary evidence concerning the medium-term prosthetic and implant success rates that may be achieved when such a membrane is used in combination with an equine, enzyme-treated bone graft, concomitantly to implant placement in the esthetic zone. Materials and Methods: Records of patients who had one or two implants placed in the anterior sectors of the two arches and had peri-implant bone regeneration carried out using the equine-derived membrane and equine-derived collagen-preserving bone granules were retrospectively collected. Peri-implant marginal bone loss (MBL) was used to assess implant survival. When available, histologic data concerning the equine membrane and cone beam computed tomography (CBCT) scans were analyzed as well. Results: Records of 32 patients (ages 36 to 73 years), corresponding to 44 implants placed, were retrieved and analyzed. The mean follow-up was 113.9 ± 10.2 months. Two implants failed. The implant success rate was 90.9%. Twelve membrane samples could be retrieved and analyzed, showing the membrane was still occlusive at 4.2 ± 1.1 months and only beginning to undergo remodeling. Twelve CBCT scans showed that 65.1 ± 9.8 months after surgery, a newly formed cortical layer could be observed in the zone that had undergone grafting. Conclusion: The equine cortical bone membrane and the enzyme-treated bone graft used in this case series achieved a medium-term implant and prosthetic success rate that was not dissimilar to that of other resorbable membranes and grafts for peri-implant guided bone regeneration augmentation. Preliminary medium-term histologic and CBCT data suggest that the membrane may be occlusive for a period of at least 4 months and may contribute to preserve the ridge thickness over time. [ABSTRACT FROM AUTHOR]

Background: To provide a reference for clinical selection of collagen membranes by analyzing the properties of three kinds of collagen membranes widely used in clinics: Bio-Gide membrane from porcine dermis (PD), Heal-All membrane from bovine dermis (BD), and Lyoplant membrane from bovine pericardium (BP). Methods: The barrier function of three kinds of collagen membranes were evaluated by testing the surface morphology, mechanical properties, hydrophilicity, and degradation rate of collagen membranes in collagenase and artificial saliva. In addition, the bioactivity of each collagen membrane as well as the proliferation and osteogenesis of MC3T3-E1 cells were evaluated. Mass spectrometry was also used to analyze the degradation products. Results: The BP membrane had the highest tensile strength and Young's modulus as well as the largest water contact angle. The PD membrane exhibited the highest elongation at break, the smallest water contact angle, and the lowest degradation weight loss. The BD membrane had the highest degradation weight loss, the highest number of proteins in its degradation product, the strongest effect on the proliferation of MC3T3-E1 cells, and the highest expression level of osteogenic genes. Conclusions: The PD membrane is the best choice for shaping and maintenance time, while the BD membrane is good for osteogenesis, and the BP membrane is suitable for spatial maintenance. To meet the clinical requirements of guided bone regeneration, using two different kinds of collagen membranes concurrently to exert their respective advantages is an option worth considering. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the potential adjunctive effect of a resorbable collagen membrane covering a xenogeneic bone replacement graft in the reconstructive surgical therapy of peri‐implantitis. Materials and Methods: Forty‐three patients (43 implants) diagnosed with peri‐implantitis associated with intra‐bony defects were treated with a surgical reconstructive approach that included a xenogeneic bone substitute material. Additionally, resorbable collagen membranes were placed over the grafting material at sites randomly allocated to the test group; conversely, no membranes were placed in the control group. Clinical outcomes, namely probing pocket depth (PPD), bleeding and suppuration on probing (BoP and SoP), marginal mucosal level (REC) and keratinized mucosa width (KMW), were recorded at baseline and 6 and 12 months after surgery. Radiographic marginal bone levels (MBLs) and patient‐reported outcomes (PROs) were assessed at baseline and 12 months. A composite outcome (success) was evaluated at 12 months, which included the absence of BoP/SoP, PPD ≤5 mm and reduction of buccal marginal mucosal level (buccal REC) of ≤1 mm. Results: At 12 months, no implants were lost and treatment success was observed at 36.8% and 45.0% of implants in the test and control groups, respectively (p =.61). Similarly, there were no significant differences between groups in terms of changes of PPD, BoP/SoP, KMW, MBL or buccal REC. Post‐surgical complications were observed in the test group only (e.g., soft tissue dehiscence, exposure of particulate bone graft and/or resorbable membrane). Longer surgical times (~10 min; p <.05) and higher levels of self‐reported pain at 2 weeks (p <.01) were observed in the test group. Conclusions: This study failed to demonstrate the presence of added clinical or radiographic benefits of the use of a resorbable membrane to cover a bone substitute material within the reconstructive surgical therapy of peri‐implantitis associated with intra‐bony defects. [ABSTRACT FROM AUTHOR]

Yiwen Dong,1– 3 Litao Yao,2– 4,&ast; Lei Cai,1 Mi Jin,1 Tymour Forouzanfar,2,3 Lianjun Wu,1 Jinsong Liu,1,&ast; Gang Wu2,3 1School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, Amsterdam, the Netherlands; 3Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Amsterdam, the Netherlands; 4Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Yao, Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Zhejiang, Email yaolt@srrsh.com Jinsong Liu, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Email jinsong0719@wmu.edu.cnIntroduction: An antibacterial and pro-osteogenic coaxially electrospun nanofiber guided bone regeneration (GBR) membrane was fabricated to satisfy the complicated and phased requirements of GBR process.Methods: In this study, we synthesize dual-functional coaxially electrospun nanofiber GBR membranes by encapsulating parathyroid hormone (PTH) in the core layer and magnesium oxide nanoparticles (MgONPs) in the shell layer (MgONPs-PCL/PTH-PCL). Herein, the physicochemical characterization of MgONPs-PCL/PTH-PCL, the release rates of MgONPs and PTH, and antibacterial efficiency of the new membrane were evaluated. Furthermore, the pro-osteogenicity of the membranes was assessed both in-vitro and in-vivo.Results: We successfully fabricated a coaxially electrospun nanofiber MgONPs-PCL/PTH-PCL membrane with the majority of nanofibers (> 65%) ranged from 0.40~0.60μm in diameter. MgONPs-PCL/PTH-PCL showed outstanding antibacterial potential against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) through the release of MgONPs. We also discovered that the incorporation of MgONPs significantly prolonged the release of PTH. Furthermore, both the in-vivo and in-vitro studies demonstrated that high dosage of PTH promoted pro-osteogenicity of the membrane to improve bone regeneration efficacy with the presence of MgONPs.Conclusion: The new composite membrane is a promising approach to enhance bone regeneration in periodontitis or peri-implantitis patients with large-volume bone defects.Keywords: antibacterial property, pro-osteogenicity, coaxially electrospun, barrier membrane, guided bone regeneration

Ping Zhao,1 Wei Chen,1 Zhangbin Feng,1 Yukang Liu,1 Ping Liu,2,3 Yufeng Xie,4 Deng-Guang Yu1,5 1School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 2The Base of Achievement Transformation, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, 200433, People’s Republic of China; 3Institute of Orthopaedic Basic and Clinical Transformation, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 4Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China; 5Shanghai Engineering Technology Research Center for High-Performance Medical Device Materials, Shanghai, 200093, People’s Republic of ChinaCorrespondence: Deng-Guang Yu; Ping Liu, Email ydg017@usst.edu.cn; liupingmedicine@163.comAbstract: Periodontitis is a major threat to oral health, prompting scientists to continuously study new treatment techniques. The nanofibrous membrane prepared via electrospinning has a large specific surface area and high porosity. On the one hand, electrospun nanofibers can improve the absorption capacity of proteins and promote the expression of specific genes. On the other hand, they can improve cell adhesion properties and prevent fibroblasts from passing through the barrier membrane. Therefore, electrospinning has unique advantages in periodontal treatment. At present, many oral nanofibrous membranes with antibacterial, anti-inflammatory, and tissue regeneration properties have been prepared for periodontal treatment. First, this paper introduces the electrospinning process. Then, the commonly used polymers of electrospun nanofibrous membranes for treating periodontitis are summarized. Finally, different types of nanofibrous membranes prepared via electrospinning for periodontal treatment are presented, and the future evolution of electrospinning to treat periodontitis is described.Graphical Abstract: Keywords: periodontitis, electrospinning, barrier membrane, antibacterial, anti-inflammatory, tissue regeneration

Barrier membranes are an essential tool in guided bone Regeneration (GBR), which have been widely presumed to have a bioactive effect that is beyond their occluding and space maintenance functionalities. A standardized calvaria implantation model was applied for 2, 8, and 16 weeks on Wistar rats to test the interactions between the barrier membrane and the underlying bone defects which were filled with bovine bone substitute materials (BSM). In an effort to understand the barrier membrane's bioactivity, deeper histochemical analyses, as well as the immunohistochemical detection of macrophage subtypes (M1/M2) and vascular endothelial cells, were conducted and combined with histomorphometric and statistical approaches. The native collagen-based membrane was found to have ossified due to its potentially osteoconductive and osteogenic properties, forming a "bony shield" overlying the bone defects. Histomorphometrical evaluation revealed the resorption of the membranes and their substitution with bone matrix. The numbers of both M1- and M2-macrophages were significantly higher within the membrane compartments compared to the underlying bone defects. Thereby, M2-macrophages significantly dominated the tissue reaction within the membrane compartments. Statistically, a correlation between M2-macropahges and bone regeneration was only found at 2 weeks post implantationem, while the pro-inflammatory limb of the immune response correlated with the two processes at 8 weeks. Altogether, this study elaborates on the increasingly described correlations between barrier membranes and the underlying bone regeneration, which sheds a light on the understanding of the immunomodulatory features of biomaterials. [ABSTRACT FROM AUTHOR]

This study evaluated surface characteristics and biocompatibility of surface-modified thin titanium (Ti) foils as a regenerative barrier membrane for future application in guided bone regeneration (GBR) surgery to augment atrophic alveolar bone. Anodic oxidation and post-heat treatment were performed to prepare various Ti foil samples. Then, the in vitro soft and hard tissue compatibility of the samples was evaluated by examining the cell responses using primary human gingival fibroblasts (HGFs) and MG63 human osteoblast-like cells. Investigated Ti foil samples showed marked differences in physicochemical surface properties. Additional 400°C heat treatment applied to the anodized Ti surface led to formation of an anatase titanium dioxide structure and well-organized nanoscale protrusions, and significantly increased surface wettability. Anodization and heat treatment enhanced the growth of HGFs and MG63 cells in Ti foil samples. Additional heat treatment for 10 and 30 min further significantly improved the response of HGFs including spreading and proliferation, and upregulated the mRNA expression of cell adhesion- and maturation-related genes as well as the osteoblast differentiation of MG63 cells. Ti foil sample with thin oxide coating obtained by a 30 min heat treatment exhibited poor clinical plasticity as a regenerative barrier membrane, which showed complete coating failure in the bending test. Our results indicate that anatase Ti oxide coating of a specific film thickness with nanoscale surface protrusion morphology and hydrophilic characteristics obtained by anodization and post-heat treatment would be an effective approach as a biocompatible Ti regenerative membrane for inducing better regeneration of both gingival tissue and bone. [ABSTRACT FROM AUTHOR]

Both guided bone and guided tissue regeneration are techniques that require the use of barrier membranes. Contamination and infection of the surgical area is one of the most feared complications. Some current lines of research focus on functionalizing these membranes with different antimicrobial agents. The objective of this study was to carry out a review of the use and antibacterial properties of regeneration membranes doped with antimicrobials such as zinc, silver, chlorhexidine, and lauric acid. The protocol was based on PRISMA recommendations, addressing the PICO question: “Do membranes doped with non-antibiotic antimicrobials have antibacterial activity that can reduce or improve infection compared to membranes not impregnated with said antimicrobial?” Methodological quality was evaluated using the RoBDEMAT tool. A total of 329 articles were found, of which 25 met the eligibility criteria and were included in this review. Most studies agree that zinc inhibits bacterial growth as it decreases colony-forming units, depending on the concentration used and the bacterial species studied. Silver compounds also decreased the secretion of proinflammatory cytokines and presented less bacterial adhesion to the membrane. Some concentrations of chlorhexidine that possess antimicrobial activity have shown high toxicity. Finally, lauric acid shows inhibition of bacterial growth measured by the disk diffusion test, the inhibition zone being larger with higher concentrations. Antimicrobial agents such as zinc, silver, chlorhexidine, and lauric acid have effective antibacterial activity and can be used to dope regenerative membranes in order to reduce the risk of bacterial colonization.

Purpose: This study evaluated the efficacy of newly designed, laser-perforated pure titanium membranes for guided bone regeneration using beta-tricalcium phosphate (β-TCP), and compared them with the existing membrane. Materials and Methods: Bilateral acute lateral ridge defects were created in the mandibles of 12 dogs (four defects per animal), which were then randomly divided into two groups (six dogs each). The twenty-four bone defects in each group were then further divided into five groups. The groups were as follows: (1) F001M0, a prototype membrane without a frame plus β-TCP (n = 5); (2) F001M1, a prototype membrane with a frame plus β-TCP (n = 5); (3) FBS, an existing control membrane plus β-TCP (n = 5); (4) control 1, β-TCP without membrane and with covering flap only (n = 5); and (5) control 2, no treatment (no β-TCP and no membrane) (n = 4). In all groups where β-TCP was used, it was mixed with peripheral blood. The animals were necropsied at 6 or 12 weeks postoperatively (six dogs each), and samples were collected and processed for radiographic, histologic, and histomorphometric analyses. Results: Among the three membrane groups, regenerated tissue and bone volume was greatest in the F001M1 group at both 6 and 12 weeks postoperatively, although differences among groups were not statistically significant. Bone mineral density was similar among the membrane groups. Histologic analysis revealed that immature fibroblasts were present on the laser-perforated portion at 6 weeks, which induced vascularization. In addition, more calcified bone was replaced beneath the prototypes than beneath the FBS membrane at 12 weeks. Histomorphometric analyses revealed that the calcific osseous areas at 12 weeks after surgery were significantly greater in the F001M1 and F001M0 groups than in the FBS group (P = .021, P = .032). Furthermore, the fibrous tissue areas beneath the membrane at 12 weeks postoperatively were significantly smaller in the prototype groups than in the FBS group (P = .02, P = .02). Conclusion: The efficacies of both prototype membranes were not inferior to that of the FBS membrane, indicating that they may facilitate bone regeneration and maturation when β-TCP mixed with autologous blood is employed. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the safety and efficacy of newly designed, laser-perforated pure titanium membranes for guided bone regeneration and to compare them with an existing product, the FRIOS BoneShield (FBS). Materials and Methods: Acute-type lateral ridge defects were bilaterally created in the mandibles of 13 dogs (two defects per animal). The defects were randomly divided into three groups and were reconstructed with particulate autologous bone (PAB) in combination with three different titanium membranes: (1) F001M0 (prototype without a frame), (2) F001M1 (prototype with a frame), and (3) FBS as a standard membrane. All animals were observed periodically and sacrificed 26 or 27 weeks postoperatively. At 26 weeks, approximately half of the dogs in each group underwent membrane removal to examine the postoperative condition of the titanium membranes. The samples were dissected and processed for radiographic, histologic, and histomorphometric analyses. Results: Membrane exposure was not found in the F001M0 or F001M1 groups, and their membranes were removed easily without adhesion to the surrounding tissue. Regenerated bone tissue volume was largest in the F001M1 group, followed by the F001M0 and FBS groups. A significant difference was observed only between the F001M1 and FBS groups (P = .047). In contrast, bone mineral density was similar among the three groups. Histologically, a layer of fibrous tissue was present underneath the titanium membrane, overlying the regenerated cortical bone in all the groups. Notably, the tissue was highly vascular in the F001M1 and F001M0 groups compared with the FBS group. In addition, there was little difference in the semiquantitative soft tissue evaluation and histologic findings of bone regeneration among the three groups. The histomorphometric analysis revealed that the regenerated bone area was larger in the F001M1 and F001M0 groups than in the FBS group, and a significant difference was observed only between the F001M1 and FBS groups (P = .045). Calcific osseous area was similar among the three groups. Conclusion: The safety and efficacy of both F001M0 and F001M1 were equivalent to or greater than those of FBS, thereby indicating their potential for future clinical applications. [ABSTRACT FROM AUTHOR]

Here we review the knowledge on the local biological immunological response (formation of “pseudo periosteum” of the host) to two types of nonresorbable membranes used in the horizontal and vertical alveolar ridge augmentation: the titanium-reinforced polytetrafluoroethylene membrane and the titanium mesh membrane. A literature search was conducted including available in vitro, in vivo, and clinical studies on cellular and molecular immunological response to these two types of nonresorbable membranes, in particular the formation of “pseudo periosteum”.Emerging data demonstrates that despite barrier membranes being considered as bioinert, they still elicit an immunological response from the body. The outcome of this reaction is the formation of a thin fibrous capsule referred to as “pseudo periosteum”.There are almost no biomaterials that are truly bioinert and this makes no exception for the nonresorbable membranes used in the guided bone regeneration. This iatrogenically made tissue is hypothesized to have a number of advantages and drawbacks. However, more research is needed in that area to truly understand its nature and importance to the guided bone regeneration process.

Scheme. 1 Schematic diagram of the principle of MB @ ZIF-8 / HA@TPU Janus membrane used for periodontal tissue regeneration. [Display omitted] • Designed and fabricated a MZHT Janus membrane with GTR, bone promoting and antibacterial effects. • ZIF-8 loaded MB was used to achieve both photodynamic and cationic synergistic antibacterial. • The MZHT Janus membrane has excellent biocompatibility and some degradability. • The use of MZHT Janus membrane significantly improves the inflammation in infected wounds in the mouth. The guided tissue regeneration (GTR) procedure has become an important process for the treatment of periodontal tissue regeneration, using the membrane as a mechanical barrier to generate a distance across the defect that subsequently allowing bone regeneration. Due to the complexity of periodontal microenvironment caused by bacterial infections, inflammation, and fibrous tissue penetration, the guided tissue regeneration membrane is required to have antibacterial and barrier functions. We developed a loaded methylene blue @ ZIF-8 and hydroxyapatite gradient thermoplastic polyurethane Janus membrane for antibacterial osteogenic and barrier. This Janus membrane with a porous gradient structure was prepared to use phase-conversion method. The rough layer facilitated cell growth and promoted periodontal bone regeneration, whereas the smooth layer isolated the growing fiber tissue.The rapid release of reactive oxygen species in the early stage and continuous release of zinc ions by methylene blue @ZIF-8 can achieve long-term synergistic antibacterial effect, with antibacterial rates of 84 % and 72 % against Escherichia coli and Staphylococcus aureus, respectively, which can effectively reduce the local inflammation caused by bacteria. In summary, we applied the Janus membrane to a rat periodontal bone defect model, and the membrane showed good surgical performance, barrier properties, osteogenic properties, and antibacterial effects, which could have broad application prospects in the treatment of periodontal bone defects. [ABSTRACT FROM AUTHOR]

Maxillary sinus augmentation with a lateral approach (MSA) is a well-established treatment. In this prospective study, we evaluated risk factors for postoperative bone graft displacement and reported the clinical application of long-term resorbable L-lactic acid/-caprolactone (PLA/PCL) as a barrier membrane to cover the open window in the lateral wall in MSA. Twenty-four patients underwent MSA according to the relevant criteria; CT data obtained before and 1 week (1 w) and 5–6 months (5 m) post-MSA, bone height changes, bone height reduction rates at 1 w and 5 m post-MSA, bone graft displacement measurements, and risk factors were examined. All patients showed bone height increments (p < 0.005). However, no difference was observed between 1 w and 5 m post-MSA. Bone graft displacement was observed in eight patients; the reduction rate from 1 w to 5 m post-MSA was 8.38% ± 4.88%. Sex, septa, maxillary sinus floor–palatal bone distance, and maxillary sinus floor–maxillary ostium distance were associated with bone graft displacement (p < 0.05). The height from the maxillary sinus floor to the palatal bone and the sinus angle influenced the augmentation degree (p < 0.05). The PLA/PCL membrane is compared favorably with other membranes and may be useful as a barrier membrane for the MSA open window.

Poly(L-lactic acid) (PLLA) and PLLA/gelatin polymers were prepared via electrospinning to evaluate the effect of PLLA and gelatin content on the mechanical properties, water uptake capacity (WUC), water contact angle (WCA), degradation rate, cytotoxicity and cell proliferation of membranes. As the PLLA concentration increased from 1 wt% to 3 wt%, the tensile strength increased from 5.8 MPa to 9.1 MPa but decreased to 7.0 MPa with 4 wt% PLLA doping. The WUC decreased rapidly from 594% to 236% as the PLLA content increased from 1 to 4 wt% due to the increased hydrophobicity of PLLA. As the gelatin content was increased to 3 wt% PLLA, the strength, WUC and WCA of the PLLA/gelatin membrane changed from 9.1 ± 0.9 MPa to 13.3 ± 2.3 MPa, from 329% to 1248% and from 127 ± 1.2° to 0°, respectively, with increasing gelatin content from 0 to 40 wt%. However, the failure strain decreased from 3.0 to 0.5. The biodegradability of the PLLA/gelatin blend increased from 3 to 38% as the gelatin content increased to 40 wt%. The viability of L-929 and MG-63 cells in the PLLA/gelatin blend was over 95%, and the excellent cell proliferation and mechanical properties suggested that the tunable PLLA/gelatin barrier membrane was well suited for absorbable periodontal tissue regeneration.

Guided tissue regeneration (GTR) and guided bone regeneration (GBR) are two common dental regenerative treatments targeted at reconstructing damaged periodontal tissue and bone caused by periodontitis. During GTR/GBR treatment, a barrier membrane is placed in the interface between the soft tissue and the periodontal defect to inhibit soft tissue ingrowth and creating a space for the infiltration of slow‐growing bone cells into the defect site. Recently, asymmetric resorbable‐based barrier membrane has received a considerable attention as a new generation of GTR/GBR membrane. Despite numerous literatures about asymmetric‐based membrane that had been published, there is lacks comprehensive review on asymmetric barrier membrane that particularly highlight the importance of membrane structure for periodontal regeneration. In this review, we systematically cover the latest development and advancement of various kinds of asymmetric barrier membranes used in periodontal GTR/GBR application. Herein, the ideal requirements for constructing a barrier membrane as well as the rationale behind the asymmetric design, are firstly presented. Various innovative methods used in fabricating asymmetric barrier membrane are being further discussed. Subsequently, the application and evaluation of various types of asymmetric barrier membrane used for GTR/GBR are compiled and extensively reviewed based on the recent literatures reported. Based on the existing gap in this field, the future research directions of asymmetric resorbable‐based barrier membrane such as its combination potential with bone grafts, are also presented. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of polycaprolactone barrier membrane can prevent the surrounding fast-growing fibrous tissue and epithelial tissue from entering the bone defect thus enhancing bone regeneration process. In addition, the osteogenic modification of the polycaprolactone barrier membrane has been explored by researchers. OBJECTIVE: To summarize the modification strategies of polycaprolactone barrier membrane, and look forward to new osteogenesis strategies. METHODS: CNKI, Wanfang, VIP, and PubMed databases were searched with key words of “polycaprolactone membrane, osteogenesis, bone substitute material, natural polymer, artificial polymer, metal ion, growth factor, stem cell” in both Chinese and English for articles regarding polycaprolactone barrier membrane published from January 2000 to February 2021. RESULTS AND CONCLUSION: The first problem to be solved for polycaprolactone is to reduce the hydrophobicity when combining with other materials. At present, many methods have been developed as connecting bridges to make polycaprolactone more compatible with other materials, such as dopamine, heparin, and collagen. However, the combination of polycaprolactone with different materials requires diverse conditions, and new hydrophobicity modification methods still need to be explored. In addition, polycaprolactone material and its modification strategies have been widely studied. The research of the incorporation of polycaprolactone with bone substitute material, natural polymer and artificial polymer has achieved pleasing results. Nevertheless, due to the limitation of osteogenesis of composite materials, new osteogenic materials still need to be developed. Presently, there are some substances (such as exosomes and extracellular matrix) that have been verified to exhibit superior osteogenic ability for many kinds of tissues, such as peripheral nerve regeneration and vascular regeneration. The incorporation of polycaprolactone with those active substances is expected to develop into new regeneration strategies for tissue engineering. [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) technology has been demonstrated to be an effective method for reconstructing bone defects. A membrane is used to cover the bone defect to stop soft tissue from growing into it. The biosurface design of the barrier membrane is key to the technology. In this work, an asymmetric functional gradient Janus membrane was designed to address the bidirectional environment of the bone and soft tissue during bone reconstruction. The Janus membrane was simply and efficiently prepared by the multilayer self-assembly technique, and it was divided into the polycaprolactone isolation layer (PCL layer, GBR-A) and the nanohydroxyapatite/polycaprolactone/polyethylene glycol osteogenic layer (HAn/PCL/PEG layer, GBR-B). The morphology, composition, roughness, hydrophilicity, biocompatibility, cell attachment, and osteogenic mineralization ability of the double surfaces of the Janus membrane were systematically evaluated. The GBR-A layer was smooth, dense, and hydrophobic, which could inhibit cell adhesion and resist soft tissue invasion. The GBR-B layer was rough, porous, hydrophilic, and bioactive, promoting cell adhesion, proliferation, matrix mineralization, and expression of alkaline phosphatase and RUNX2. In vitro and in vivo results showed that the membrane could bind tightly to bone, maintain long-term space stability, and significantly promote new bone formation. Moreover, the membrane could fix the bone filling material in the defect for a better healing effect. This work presents a straightforward and viable methodology for the fabrication of GBR membranes with Janus-based bioactive surfaces. This work may provide insights for the design of biomaterial surfaces and treatment of bone defects.

Bone substitutes and barrier membranes are widely used in dental regeneration procedures. New materials are constantly being developed to provide the most optimal surgical outcomes. One of these developments is the addition of hyaluronate (HA) to the bovine bone graft, which has beneficial wound healing and handling properties. However, an acidic environment that is potentially produced by the HA is known to increase the degradation of magnesium metal. The aim of this study was to evaluate the potential risk for the addition of HA to the bovine bone graft on the degradation rate and hence the efficacy of a new biodegradable magnesium metal GBR membrane. pH and conductivity measurements were made in vitro for samples placed in phosphate-buffered solutions. These in vitro tests showed that the combination of the bovine graft with HA resulted in an alkaline environment for the concentrations that were used. The combination was also tested in a clinical setting. The use of the magnesium metal membrane in combination with the tested grafting materials achieved successful treatment in these patients and no adverse effects were observed in vivo for regenerative treatments with or without HA. Magnesium based biodegradable GBR membranes can be safely used in combination with bovine graft with or without hyaluronate.

This study aimed to evaluate the usefulness of a novel titanium membrane (Ti honeycomb membrane), which has ultrafine structures with dense microperforations, for the alveolar bone augmentation including guided bone regeneration (GBR). Fifteen patients with 17 bone defects underwent alveolar bone augmentation surgery using the membranes with autologous bone grafting plus beta-tricalcium phosphate (β-TCP) (n = 9) or with β-TCP alone (n = 8). The membranes were removed at 6–8 months postoperatively, and the regenerated bone was evaluated clinically. In addition, the prognosis of the implants placed in the augmented bones was assessed. Postoperative courses were uneventful in 14 sites without membrane exposures, in which CT analysis showed the bone volume required to place the implants and significantly higher bone density in the sites with autologous bone grafting plus β-TCP than in the sites with β-TCP alone (p = 0.019). In contrast, membrane exposures were found in three sites (17.6%) at< 4 weeks postoperatively (early membrane exposure) and the bone augmentations resulted in failure; however, implants could be placed in two of the three sites. Finally, the overall success rate of bone augmentation and implants placed in the augmented bone were 82.4% and 93.3%, respectively. This membrane was proved to be useful for alveolar bone augmentation, especially when using autologous bone grafting plus β-TCP; however, more efficient operative techniques are required to prevent early membrane exposure. [ABSTRACT FROM AUTHOR]

This study evaluated the in vitro biocompatibility of a novel, semi-rigid shell barrier system for guided bone regeneration (GBR) based on polycaprolactone and biphasic calcium phosphate membranes and consisting of a semi-rigid shell (SR) and two semi-resorbable barrier membranes, i.e., a buffered (BF) and an airdried (AD) membrane. In vitro biocompatibility, cell cytotoxicity, cell proliferation and differentiation were evaluated with osteoblast (MC3T3-E1) and fibroblast (L929) cells compared to the d-PTFE membrane (Cytoplast®, CP). The osteoblasts and fibroblasts were well attached and proliferated on all materials from days 1, 3, and 7 without cell cytotoxicity. All groups showed that osteoblast and fibroblast cell proliferation increased from day 1 to day 14–17 and decreased on day 21. On day 21, the CP membrane presented significantly higher osteoblast cell numbers than the BF membrane and the SR shell (p = 0.000). The CP membrane presented a significantly higher amount of fibroblast cells than the other groups (p = 0.000). The SR shell and the BF membrane demonstrated higher osteoblast cell differentiation markers including ALP activity, osteocalcin, and mineral secretion than the CP and the AD membrane. The semi-rigid shell barrier system demonstrated good in vitro biocompatibility and supported osteogenic cell proliferation and differentiation better than the d-PTFE membrane. [ABSTRACT FROM AUTHOR]

Background and Objective: The clinical outcomes of guided tissue regeneration (GTR) or guided bone regeneration (GBR) procedures can be impaired if a bacterial infection develops at the surgical site. Membrane exposure is one of the causes of the onset of bacterial infection. Previously, we have fabricated a poly(lactic acid/caprolactone) (PLCL) bilayer membrane composed of a porous layer and a compact layer. The compact layer acts as a barrier against connective tissue and epithelial cells, and we hypothesized that it could also be an effective barrier against bacterial cells. The objective of this study was to evaluate the ability of the PLCL bilayer membrane to block bacterial cell penetration, which would be useful for preventing postoperative infections. Methods: Porphyromonas gingivalis, Streptococcus mutans, and multispecies bacteria collected from human saliva were used in this study. Bacteria were seeded directly on the compact layer of a PLCL bilayer membrane, and bacterial adhesion to the membrane, as well as penetration into the membrane's structure, were assessed. Bacterial adhesion was evaluated by the number of colonies formed at 6, 24, and 72 h, and penetration was observed using a scanning electron microscope at 24 and 72 h. Commercially available membranes, composed of poly(lactic‐co‐glycolic acid) or type I collagen, were used as controls. Results: P. gingivalis, S. mutans, and the multispecies bacteria obtained from human saliva adhered onto all the membranes after only 6 h of incubation. However, fewer adherent cells were observed for the PLCL bilayer membrane compared with the controls for all experimental periods. The PLCL membrane was capable of blocking bacterial penetration, and no bacterial cells were observed in the structure. In contrast, bacteria penetrated both the control membranes and were observed at depths of up to 80 µm after 72 h of incubation. Conclusion: Membrane characteristics may influence how bacterial colonization occurs. The PLCL membrane had reduced bacterial adhesion and blocked bacterial penetration, and these characteristics could contribute to a favorable outcome for regenerative treatments. In the event of membrane exposure at GTR/GBR surgical sites, membranes with an efficient barrier function, such as the PLCL bilayer membrane, could simplify the management of GTR/GBR complications. [ABSTRACT FROM AUTHOR]

The adjunctive use of GTR membranes helps us to achieve predictable periodontal regeneration. The aim of this systematic review was to evaluate and compare the treatment efficacy of resorbable versus non-resorbable barrier membranes used in guided tissue regeneration in the treatment of intrabony defects in chronic periodontitis patients. The following databases were searched: Medline, the Cochrane Central Register of Controlled Trails (CENTRAL), SCOPUS, EMBASE. Randomized clinical trials (RCTs) published in English languages over the past 25 years were included. The primary outcomes assessed were: change of probing pocket depth (PD), change in clinical attachment level (CAL) and gingival recession coverage (GRC), and intrabony defect fill (IBDF). A total of eight RCTs were included for systematic review. The outcome of GR at a six-month interval revealed a significant difference in treatment effect with a mean difference of 0.42, 95% CI [0.02, 0.81]; Z = 2.09, (p = 0.04) favouring the resorbable membrane group. The intrabony defect depth fill at a 12-month interval revealed a significant difference in treatment effect with MD of 0.79, p = 0.00001; favoring the resorbable membrane group. The resorbable membrane showed a significant improvement in gingival recession coverage and intrabony defect fill, owing to its advantage of avoiding the second surgical intervention. [ABSTRACT FROM AUTHOR]

Sufficient bone volume is indispensable to achieve functional and aesthetic results in the fields of oral oncology, trauma, and implantology. Currently, guided bone regeneration (GBR) is widely used in reconstructing the alveolar ridge and repairing bone defects owing to its low technical sensitivity and considerable osteogenic effect. However, traditional barrier membranes such as collagen membranes or commercial titanium mesh cannot meet clinical requirements, such as lack of space-preserving ability, or may lead to more complications. With the development of digitalization and three-dimensional printing technology, the above problems can be addressed by employing customized barrier membranes to achieve space maintenance, precise predictability of bone graft, and optimization of patient-specific strategies. The article reviews the processes and advantages of three-dimensional computer-assisted surgery with GBR in maxillofacial reconstruction and alveolar bone augmentation; the properties of materials used in fabricating customized bone regeneration sheets; the promising bone regeneration potency of customized barrier membranes in clinical applications; and up-to-date achievements. This review aims to present a reference on the clinical aspects and future applications of customized barrier membranes.

Guided bone regeneration (GBR) is a widely used technique for alveolar bone augmentation. Among all the principal elements, barrier membrane is recognized as the key to the success of GBR. Ideal barrier membrane should have satisfactory biological and mechanical properties. According to their composition, barrier membranes can be divided into polymer membranes and non-polymer membranes. Polymer barrier membranes have become a research hotspot not only because they can control the physical and chemical characteristics of the membranes by regulating the synthesis conditions but also because their prices are relatively low. Still now the bone augment effect of barrier membrane used in clinical practice is more dependent on the body’s own growth potential and the osteogenic effect is difficult to predict. Therefore, scholars have carried out many researches to explore new barrier membranes in order to improve the success rate of bone enhancement. The aim of this study is to collect and compare recent studies on optimizing barrier membranes. The characteristics and research progress of different types of barrier membranes were also discussed in detail.

Periodontal treatment of tissue defects which comprises guided tissue regeneration and mucosal plastic surgery still remains nowadays a challenge in the dental office due to the lack of absolute predictability. New treatment techniques and biomaterials have emerged in order to counteract the different risks generated by the periodontal surgical methods. 3D and 4D printing technologies offer new possibilities in terms of patient-tailored materials, with lower complications and trauma and with the promise of a more accurate treatment plan and success.

Barrier membranes are an essential tool in guided bone Regeneration (GBR), which have been widely presumed to have a bioactive effect that is beyond their occluding and space maintenance functionalities. A standardized calvaria implantation model was applied for 2, 8, and 16 weeks on Wistar rats to test the interactions between the barrier membrane and the underlying bone defects which were filled with bovine bone substitute materials (BSM). In an effort to understand the barrier membrane’s bioactivity, deeper histochemical analyses, as well as the immunohistochemical detection of macrophage subtypes (M1/M2) and vascular endothelial cells, were conducted and combined with histomorphometric and statistical approaches. The native collagen-based membrane was found to have ossified due to its potentially osteoconductive and osteogenic properties, forming a “bony shield” overlying the bone defects. Histomorphometrical evaluation revealed the resorption of the membranes and their substitution with bone matrix. The numbers of both M1- and M2-macrophages were significantly higher within the membrane compartments compared to the underlying bone defects. Thereby, M2-macrophages significantly dominated the tissue reaction within the membrane compartments. Statistically, a correlation between M2-macropahges and bone regeneration was only found at 2 weeks post implantationem, while the pro-inflammatory limb of the immune response correlated with the two processes at 8 weeks. Altogether, this study elaborates on the increasingly described correlations between barrier membranes and the underlying bone regeneration, which sheds a light on the understanding of the immunomodulatory features of biomaterials.

The fast degradation of collagen-based membranes in the biological environment remains a critical challenge, resulting in underperforming Guided Bone Regeneration (GBR) therapy leading to compromised clinical results. Photoactive atelocollagen (AC) systems functionalised with ethylenically unsaturated monomers, such as 4-vinylbenzyl chloride (4VBC), have been shown to generate mechanically competent materials for wound healing, inflammation control and drug delivery, whereby control of the molecular architecture of the AC network is key. Building on this platform, the sequential functionalisation with 4VBC and methacrylic anhydride (MA) was hypothesised to generate UV-cured AC hydrogels with reduced swelling ratio, increased proteolytic stability and barrier functionality for GBR therapy. The s equentially functionalised a telocollagen p recursor (SAP) was characterised via TNBS and ninhydrin colourimetric assays, circular dichroism and UV-curing rheometry, which confirmed nearly complete consumption of collagen's primary amino groups, preserved triple helices and fast (< 180 s) gelation kinetics, respectively. Hydrogel's swelling ratio and compression modulus were adjusted depending on the aqueous environment used for UV-curing, whilst the sequential functionalisation of AC successfully generated hydrogels with superior proteolytic stability in vitro compared to both 4VBC-functionalised control and the commercial dental membrane Bio-Gide®. These in vitro results were confirmed in vivo via both subcutaneous implantation and a proof-of-concept study in a GBR calvarial model, indicating integrity of the hydrogel and barrier defect, as well as tissue formation following 1-month implantation in rats. Collagen-based membranes remain a key component in Guided Bone Regeneration (GBR) therapy, but their properties, e.g. proteolytic stability and soft tissue barrier functionality, are still far from optimal. This is largely attributed to the complex molecular configuration of collagen, which makes chemical accessibility and structure-function relations challenging. Here, we fabricated a UV-cured hydrogel network of atelocollagen, whereby triple helices were sequentially functionalised with two distinct ethylenically unsaturated monomers. The effects of the sequential functionalisation and UV-curing on the macroscopic properties, degradation behaviour and GBR capability were investigated in vitro and in vivo. The results highlight the key role of the sequential functionalisation and provide important insights for the design of future, longer-lasting resorbable membranes for GBR therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: In dentistry, barrier membranes are used for guided tissue regeneration (GTR) and guided bone regeneration (GBR). Various membranes are commercially available and extensive research and development of novel membranes have been conducted. In general, membranes are required to provide barrier function, biosafety, biocompatibility and appropriate mechanical properties. In addition, membranes are expected to be bioactive to promote tissue regeneration. Objectives: This review aims to organize the fundamental characteristics of the barrier membranes that are available and studied for dentistry, based on their components. Results: The principal components of barrier membranes are divided into nonbiodegradable and biodegradable materials. Nonbiodegradable membranes are manufactured from synthetic polymers, metals or composites of these materials. The first reported barrier membrane was made from expanded polytetrafluoroethylene (e-PTFE). Titanium has also been applied for dental regenerative therapy and shows favorable barrier function. Biodegradable membranes are mainly made from natural and synthetic polymers. Collagens are popular materials that are processed for clinical use by cross-linking. Aliphatic polyesters and their copolymers have been relatively recently introduced into GTR and GBR treatments. In addition, to improve the tissue regenerative function and mechanical strength of biodegradable membranes, inorganic materials such as calcium phosphate and bioactive glass have been incorporated at the research stage. Conclusions: Currently, there are still insufficient guidelines for barrier membrane choice in GTR and GBR, therefore dentists are required to understand the characteristics of barrier membranes.

Fatemeh Ejeian,1,2 Amir Razmjou,1,3 Mohammad Hossein Nasr-Esfahani,2 Munirah Mohammad,3 Fereshteh Karamali,2 Majid Ebrahimi Warkiani,4 Mohsen Asadnia,5 Vicki Chen6 1Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 73441-81746, Iran; 2Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran; 3UNESCO Center for Membrane Technology, School of Chemical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia; 4School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia; 5School of Engineering, Macquarie University, Sydney, NSW, 2109, Australia; 6School of Chemical Engineering, University of Queensland, Brisbane, QLD, 4072, AustraliaCorrespondence: Amir RazmjouUNESCO Center for Membrane Technology, School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, AustraliaTel +61 (2) 9385 4341Fax +61 (2) 9385 5966Email amirr@unsw.edu.auMohammad Hossein Nasr-Esfahani Department of Animal Biotechnology, Cell Science Research CenterRoyan Institute for Biotechnology, ACECR, Isfahan, IranTel +98 31 95015680Fax +98 31 95015687Email mh.nasr-esfahani@royaninstitute.orgPurpose: Despite the significant advances in modeling of biomechanical aspects of cell microenvironment, it remains a major challenge to precisely mimic the physiological condition of the particular cell niche. Here, the metal–organic frameworks (MOFs) have been introduced as a feasible platform for multifactorial control of cell-substrate interaction, given the wide range of physical and mechanical properties of MOF materials and their structural flexibility.Results: In situ crystallization of zeolitic imidazolate framework-8 (ZIF-8) on the polydopamine (PDA)-modified membrane significantly raised surface energy, wettability, roughness, and stiffness of the substrate. This modulation led to an almost twofold increment in the primary attachment of dental pulp stem cells (DPSCs) compare to conventional plastic culture dishes. The findings indicate that polypropylene (PP) membrane modified by PDA/ZIF-8 coating effectively supports the growth and proliferation of DPSCs at a substantial rate. Further analysis also displayed the exaggerated multilineage differentiation of DPSCs with amplified level of autocrine cell fate determination signals, like BSP1, BMP2, PPARG, FABP4, ACAN, and COL2A. Notably, osteogenic markers were dramatically overexpressed (more than 100-folds rather than tissue culture plate) in response to biomechanical characteristics of the ZIF-8 layer.Conclusion: Hence, surface modification of cell culture platforms with MOF nanostructures proposed as a powerful nanomedical approach for selectively guiding stem cells for tissue regeneration. In particular, PP/PDA/ZIF-8 membrane presented ideal characteristics for using as a barrier membrane for guided bone regeneration (GBR) in periodontal tissue engineering.Keywords: metal–organic framework, mesenchymal stem cell, ZIF-8, cell culture platform, barrier membrane

Guided bone regeneration (GBR) barrier membranes are of great significance for the reconstruction of the health and function of different periodontal tissues. Biocompatibility, spatial maintenance, closure, controllability and biological activation are the main criteria that should be met by these membranes. Artificial barrier membrane biomaterials can be divided into synthetic polymer materials, natural polymer materials and metals. According to their degradation characteristics, these membranes can be divided into two categories, absorbable and nonabsorbable membranes. GBR used for horizontal bone increments can be used to treat various types of bone defects, including the treatment of bone fenestration and bone cracking. The use of a non-absorbable e-PTFE membrane or absorbable collagen membrane can achieve the expected effect. However, for incremental or vertical bone growth at the alveolar crest, the use of this membrane is very challenging and requires good strength to maintain the osteogenic space. This space can be enhanced with e-PTFE or d-PTFE membranes with stable morphology, or absorbable membranes can be covered with titanium plates or meshes to achieve vertical bone increments. Currently, bioactive membranes, digital 3D-printed titanium membranes and piezoelectric active biological membranes are research hotspots. In future research, the biological activation of these membranes will be further improved, which will promote the development of artificial membranes in the next stage.

Purpose To test whether or not alveolar ridge preservation (ARP) changes the clinical attachment level (CAL) at adjacent teeth of extraction sockets after 6 months. Material and methods: Seventeen patients requiring bilateral tooth extractions of the upper molars were recruited. After tooth extraction, the sockets were randomly allocated to two groups applying a split‐mouth design: (1) ARP using deproteinized bovine bone mineral containing 10% collagen (DBBM‐C) covered by a collagen membrane and (2) spontaneous healing (control). CAL, probing pocket depth (PD), bleeding on probing (BOP), gingival recession (REC), and bone levels were evaluated at the adjacent teeth of the extraction sockets at baseline and after 6 months of follow‐up. Results: A total of 14 patients were available for reexamination. From baseline to 6 months of follow‐up mean CAL changes of all six sites at adjacent teeth of the extraction sockets amounted to −0.23 ± 0.65 mm (gain) in ARP group and 0.05 ± 0.86 mm (loss) in the control group with significant differences in favor of ARP (p = 0.04). The CAL gain was significantly more favorable at mesiopalatal sites (p = 0.01). Consistently, the mean reduction of PD of all six sites amounted to −0.68 ± 0.84 mm in ARP and −0.34 ± 0.74 mm in the control group (intergroup p = 0.02). The PD reduction was significant (p = 0.001) at the mesiopalatal sites in ARP. BOP, REC, and bone levels showed no significant differences between the groups (intergroup p > 0.05). Conclusion: Although ARP with DBBM‐C revealed a trend toward CAL gain and PD reduction at adjacent teeth of extraction sites, these adjunctive benefits seem to be clinically negligible. [ABSTRACT FROM AUTHOR]

Schematic 1. Illustration of proposed mechanisms by which bredigite-containing scaffolds provide a dynamic immuno-modulatory and repair-supportive microenvironment for guided bone regeneration. [Display omitted] • BRT-containing scaffold as a potential GBR barrier membrane. • scRNA-seq revealing responses of BMSCs to BRT. • Osteo-immunomodulatory property of BRT-containing scaffolds in GBR. Barrier membranes play an important role in guided bone regeneration (GBR) and have been primarily considered as physical barriers. Due to their inherent "foreign body" properties, barrier membranes introduced during GBR procedures unavoidably modify the local immune microenvironment, with consequent impacts on osteogenesis. In bone tissue engineering applications, inorganic bioceramics have been shown to possess the abilities to modulate the local immune response and promote the differentiation of stem cells along osteogenic lineages. Moreover, these bioceramics can be easily incorporated into scaffold membranes, thus demonstrating significant potential as a barrier membrane material for GBR. Herein, an inorganic bredigite (BRT, Ca 7 MgSi 4 O 16) bioceramic-containing scaffold was fabricated and characterized, and its effects on the immune response and osteogenesis during GBR were investigated. The results indicated that the BRT-containing scaffolds promoted the migration and osteogenic differentiation of bone marrow-derived stem cells (BMSCs). Single-cell RNA sequencing analysis indicated a unique microenvironment and subpopulation of BMSCs cultured on the BRT scaffolds, which exhibited increased osteo/chondrogenic and angiogenic differentiation potential. Furthermore, the BRT-containing scaffolds induced macrophage polarization into the pro-regenerative M2 phenotype, which subsequently promoted the migration and osteogenic differentiation of BMSCs. Additionally, in an in vivo rat model, the BRT-containing membrane was confirmed to enhance the immune microenvironment and support bone regeneration in a cranial critical-size defect. Collectively, these findings indicate that the BRT-containing scaffold membrane possesses dual immunomodulatory and osteogenic properties, offering a potentially beneficial GBR membrane for clinical application. [ABSTRACT FROM AUTHOR]

Postoperative abdominal adhesions often occur after abdominal surgery; barrier membranes which mimic peritoneal tissue can be constructed to prevent abdominal adhesions. To this end, silk fibroin (SF) sheets were coated with polyvinyl alcohol (PVA) and agarose (AGA) at PVA:AGA ratios of 100:0, 70:30, 50:50, 30:70, and 0:100 to create a composite anti-adhesive barrier and allow us to identify a suitable coating ratio. The membranes were characterized in terms of their molecular organization, structure, and morphology using Fourier transform Infrared spectrometer (FT-IR), differential scanning calorimeter (DSC), and scanning electron microscope (SEM), respectively. The physical and mechanical properties of the membranes and their biological performance (i.e., fibroblast proliferation and invasion) were tested in vitro. Each membrane showed both smooth and rough surface characteristics. Membranes coated with PVA:AGA at ratios of 100:0, 70:30, 50:50, and 30:70 exhibited more –OH and amide III moieties than those coated with 0:100 PVA:AGA, which consequently affected structural organization, degradation, and fibroblast viability. The 0:100 PVA:AGA-coated degraded the fastest. Barrier membranes coated with 100:0 and 70:30 PVA: AGA demonstrated reduced fibroblast proliferation and attachment. The membrane coated with 70:30 PVA:AGA exhibited a stable appearance, and did not curl under wet conditions. Therefore, SF sheets coated with 70:30 PVA:AGA show promise as anti-adhesive barrier membranes for further development. [ABSTRACT FROM AUTHOR]