Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been ...Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point CT scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.展开更多
BACKGROUND Bone grafts have been applied for many years in orthopedic surgery to assist with bone repair for defects or bone discontinuity caused by trauma and tumors as well as periodontal defects.Jaw cysts are anoth...BACKGROUND Bone grafts have been applied for many years in orthopedic surgery to assist with bone repair for defects or bone discontinuity caused by trauma and tumors as well as periodontal defects.Jaw cysts are another common benign disease of the maxillofacial region which may lead to pathological bone fracture,loss of teeth,and infection.However,whether bone grafts are beneficial for bone regeneration in jaw cystic lesions and when bone grafts should be used remains unclear.AIM To study the efficacy of bone grafts compared to spontaneous healing in the treatment of jaw cystic lesions.METHODS A literature search was performed in Medline,Cochrane Library and Embase to identify related articles published in English in the last ten years.The following key words and Me SH terms were used:“jaw cyst”,“cystic lesion”,“odontogenic cyst”,“periapical cyst”,“dentigerous cyst”,“follicular cyst”,“keratocyst”,“treatment”,“surgery”,“bone graft”,“enucleation”,“cystectomy”,and“bone regeneration”.Case reports,clinical trials,clinical studies,observational studies and randomized controlled trials were included.Study quality was evaluated.RESULTS Ten studies(n=10)met the inclusion criteria.Five studies reported spontaneous bone healing after enucleation,three studies investigated the efficacy of various bone grafts,and two randomized comparative studies focused on the comparison between spontaneous healing and bone grafting.Over 90%of bone regeneration occurred within 6 mo after bone grafting.The bone regeneration rate after cystectomy showed great variation,ranging from 50%to 100%after 6 mo,but reaching over 90%after 12 mo.CONCLUSION While the long-term superiority of bone grafting compared with spontaneous healing after cystectomy is unclear,bone grafts accelerate the process of healing and significantly increase bone quality.展开更多
Purpose: To investigate the periapical tissue response after root end filling with intermediate restorative material (IRM) and filling of the root-end resection bone defects with autogenous bone or a bone graft substi...Purpose: To investigate the periapical tissue response after root end filling with intermediate restorative material (IRM) and filling of the root-end resection bone defects with autogenous bone or a bone graft substitute in comparison to empty controls. Materials and Methods: Vital roots of the second, third and fourth mandibular premolars in six healthy mongrel dogs were apectomized. The root canals were prepared and sealed with IRM following a standardized surgical procedure. The resection bone defects were either filled with autogenous bone (PB) or one of the bone graft substitutes;CERAMENTTM|BONE VOID FILLER, ChronOS?, TigranTM PTG, Easygraft? CLASSIC or left empty. After 120 days the animals were sacrificed and the specimens were analyzed radiologically and histologically. Kruskal-Wallis and Mann-Whitney tests were performed for statistical evaluation. Results: 34 sections were analyzed histologically. The evaluation revealed a variation in the outcome amongst the tested options, regarding reestablishment of the periapical bone healing and inflammatory infiltration in the sections. According to the tested variables, there was no statistical significant difference between the materials when comparing all groups as a whole. When comparing individual materials to each other there was statistical differences among some of the tested materials. Conclusion: The healing outcome after periapical surgery of a five-wall resection defect could not be increased by infill with autogenous bone or bone graft substitutes. The most important factor for the healing outcome in periapical surgery is the quality of the root-end sealing. The healing outcome after some of the tested bone substitutes, might be improved by longer healing time.展开更多
Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologi...Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologic reactions,infection risks,and geometrical mismatching concerns hampered tissue graft use and underscored the need for scaffolds for more effective bone reconstructions due to their tunable properties.Significant progress has been carried out in past decade in the fields of nanoceramics synthesis,bioconjugate chemistry,and composite material processing.This review outlines hierarchical structures and biology of bone tissue,materialistic compo-nents of scaffolds(bioceramics,polymers,bioactive drugs),featured scaffolding strategies(nanofibers,hydrogels,aerogels,bioprinting,and fiber-reinforced composite),and emphasis that hierarchical and physiochemical char-acteristics of bone should be used as an inspiration for scaffold design.This review discussed how differences in materiobiological aspects of scaffolds,such as polymer/bioceramic nanocomposite,mineralized nanocomposite,matrix-rich nanocomposite,3D microenvironmental cues,pore space cues,mechanical cues,usage of physical stimulation(magnetic,electroactive,and photoactivated cues),surface cues(wettability,roughness,textured,and surface charge),and biointerface cues(cell-biomaterial interactions,cell-selective homing,and cell regula-tory strategies)modulate cellular and biological response for bone tissue engineering.This study further outlines the challenges and benefits of integrating materiobiological cues of scaffolds for bone tissue engineering.展开更多
Recently, porous titanium granules (PTGs) have been indicated for the preservation of the dimensions of post-extraction sockets, as a filler in sinus lift procedures and for the treatment of peri-implant and periodo...Recently, porous titanium granules (PTGs) have been indicated for the preservation of the dimensions of post-extraction sockets, as a filler in sinus lift procedures and for the treatment of peri-implant and periodontal defects, based on the osteoconductivity and dimensional stability of the titanium granules. However, there is a lack of information regarding the use of this material in larger defects and in conjunction with membranes. The objective of this study is to test the behavior of PTGs used to fill critical size defects in rabbit tibiae, with and without membranes. Critical defects were created in both tibiae of rabbits, divided randomly into three groups: Group A (defect filled with PTG), Group B (defect filled with PTG+collagen membrane) and a control group (empty defect). After six weeks, histomorphometric analysis was performed. The results showed more defect closures at the cortical area (87.37%±2.2%) and more bone formation at the marrow area (57.6%± 1.3%) in Group B, in comparison with the other groups (P〈0.05); the use of membranes improved the material stability expressed as more percentages of the original material when membranes were used (P〈0.05). Finally, inflammatory reactions were observed when the granules were not protected by membranes. In spite of the limitations of this animal study, it may be concluded that PTG particles are osteoconductive and allow bone growth. The PTG particles must be covered by a membrane, especially when grafting larger defects, in order to control particle migration, promote clot stabilization and separate the PTG graft from undesired soft tissue cells.展开更多
Objective: To prepare hydroxyapatite cement (or calcium phosphate cement, CPC) and analyze its capability. Methods: Tetracalcium phosphate (TTCP) was prepared by the method of high heat. TTCP reacted with in simulated...Objective: To prepare hydroxyapatite cement (or calcium phosphate cement, CPC) and analyze its capability. Methods: Tetracalcium phosphate (TTCP) was prepared by the method of high heat. TTCP reacted with in simulated body situation and produced CPC, Its capability was analyzed by scanning electron microscopy (SEM) , X-ray diffraction(XRD). Its density, absorbing water coefficient, macroporosity and campressive strength were measured also. Results: The main element of CPC is hydroxyapatite (HA) , its microstructure comprised of needlelike or petal crystals. The diameter of micropore was 4-10 nm, density was 1.922 g/cm3, macroporosity was 29. 777% , absorbing coefficient was 15. 503%, compressive strength was 42. 70 Mpa. Conclusion: This CPC has three-dimensional spatial structure, its strength meets the need of cancellous bone grafting.展开更多
BACKGROUND In this case study,a minimally invasive transalveolar approach using platelet-rich fibrin and bone substitute with simultaneous implantation was carried out in an elderly patient.We analyzed the cone-beam c...BACKGROUND In this case study,a minimally invasive transalveolar approach using platelet-rich fibrin and bone substitute with simultaneous implantation was carried out in an elderly patient.We analyzed the cone-beam computed tomography(CBCT)findings to evaluate bone regeneration.CASE SUMMARY A 65-year-old female with no contraindications for dental implants and loss of maxillary bilateral molars is described.Examination by CBCT showed the available vertical bone height in the bilateral posterior maxilla was 0.5-6.8 mm in the left and 2.8-6.5 mm in the right.The patient underwent a transalveolar approach using platelet-rich fibrin and bone substitute with simulataneous placement of an implant 10 mm in length.Six months post-surgery,the implant showed excellent osseointegration with the bone graft.Thereafter,full-ceramic crowns were fitted.Follow-up at 2 years demonstrated satisfactory prognosis.CONCLUSION Platelet-rich fibrin and bone substitute can be used to augment the maxillary sinus with a vertical bone height less than 4 mm.展开更多
Bone grafts have been predominated used to treat bone defects,delayed union or non-union,and spinal fusion in orthopaedic clinically for a period of time,despite the emergency of synthetic bone graft substitutes.Never...Bone grafts have been predominated used to treat bone defects,delayed union or non-union,and spinal fusion in orthopaedic clinically for a period of time,despite the emergency of synthetic bone graft substitutes.Nevertheless,the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies.Hence,the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important.To address this problem,addition of various growth factors,such as bone morphogenetic proteins(BMPs),parathyroid hormone(PTH)and platelet rich plasma(PRP),into structural allografts and synthetic substitutes have been considered.Although clinical applications of these factors have exhibited good bone formation,their further application was limited due to high cost and potential adverse side effects.Alternatively,bioinorganic ions such as magnesium,strontium and zinc are considered as alternative of osteogenic biological factors.Hence,this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.展开更多
This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually...This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/ healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.展开更多
Revision total hip arthroplasty(THA)with massive bone loss has been a real challenge for orthopaedic surgeons.Here we describe an approach using mineralized collagen(MC)graft to reconstruct acetabulum and femur with m...Revision total hip arthroplasty(THA)with massive bone loss has been a real challenge for orthopaedic surgeons.Here we describe an approach using mineralized collagen(MC)graft to reconstruct acetabulum and femur with massive bone defects.We identified 89 patients suffering acetabular or femoral bone defects after primary THA,who required revision THA for this study.During the surgery,MC was applied to reconstruct both the acetabular and femoral defects.Harris hip score was used to evaluate hip function while radiographs were taken to estimate bone formation in the defect regions.The average follow-up period was 33.662.4 months.None of the components needed re-revised.Mean Harris hip scores were 42.563.5 before operation,75.264.0 at 10th month and 95.063.6 at the final follow-up.There were no instances of deep infection,severe venous thrombosis or nerve palsy.The present study demonstrated that MC graft can serve as a promising option for revision THA with massive bone deficiency.Meanwhile,extended follow-up is needed to further prove its long-term performance.展开更多
This study investigated clinical outcomes of biomimetic mineralized collagen artificial bone putty for bone reconstruction in the treatment of calcaneus fracture.Sixty cases of calcaneal fractures surgically treated w...This study investigated clinical outcomes of biomimetic mineralized collagen artificial bone putty for bone reconstruction in the treatment of calcaneus fracture.Sixty cases of calcaneal fractures surgically treated with open reduction and internal fixation in our hospital from June 2014–2015 were chosen and randomly divided into two groups,including 30 cases treated with biomimetic mineralized collagen artificial bone putty as treatment group,and 30 cases treated with autogenous ilia as control group.The average follow-up time was 17.263.0 months.The results showed that the surgery duration and postoperative drainage volume of treatment group were significantly lower than control group;there were no statistically significant differences in the fracture healing time,American Orthopaedic Foot and Ankle Society scores at 3 and 12 months after surgery,Bo¨hler’s angle,Gissane’s angle and height of calcaneus between the two groups.There were no significant differences in wound complication and reject reaction between the two groups,while significant difference in donor site complication.As a conclusion,the implantation of biomimetic mineralized collagen artificial bone putty in the open reduction of calcaneal fracture resulted in reliable effect and less complications,which is suitable for clinical applications in the treatment of bone defect in calcaneal fractures.展开更多
Porous architecture in bone substitutes,notably the interconnectivity of pores,is a critical factor for bone ingrowth.However,controlling the pore interconnectivity while maintaining the microarchitecture has not yet ...Porous architecture in bone substitutes,notably the interconnectivity of pores,is a critical factor for bone ingrowth.However,controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods,such as sintering.Herein,we fabricated a porous block using the crystal growth of calcium sulfate dihydrate,and controlled the pore interconnectivity by limiting the region of crystal growth.The calcium sulfate dihydrate blocks were transformed to bone apatite,carbonate apatite(CO_(3)Ap)through dissolution–precipitation reactions.Thus,CO_(3)Ap blocks with 15%and 30%interconnected pore volumes were obtained while maintaining the microarchitecture:they were designated as CO_(3)Ap-15 and CO_(3)Ap-30,respectively.At 4 weeks after implantation in a rabbit femur defect,new bone formed throughout CO_(3)Ap-30,whereas little bone was formed in the center region of CO_(3)Ap-15.At 12 weeks after implantation,a large portion of CO_(3)Ap-30 was replaced with new bone and the boundary with the host bone became blurred.In contrast,CO_(3)Ap-15 remained in the defect and the boundary with the host bone was still clear.Thus,the interconnected pores promote bone ingrowth,followed by replacement of the material with new bone.These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.展开更多
Bone graft substitutes are widely-studied as alternatives to bone grafts in the clinic. The currently available products are mostly ceramics and polymers. Considerable progress has been made in the study of the biodeg...Bone graft substitutes are widely-studied as alternatives to bone grafts in the clinic. The currently available products are mostly ceramics and polymers. Considerable progress has been made in the study of the biodegradable magnesium alloys, which possess the necessary attributions of a suitable substitute, including an excellent mechanical property. In the present study, a minipig model of a lateral tibial plateau defect was used to evaluate the effectiveness of a magnesium alloy in the repair of a critical-sized defect. The micro-arc oxidation (MAO)-coated ZK60 alloy tablets and medical-grade calcium sulfate pellets were used as the test and control materials, respectively. Bone morphology was monitored by computed tomography after the implantation for 2 and 4 months. It was found that the bone morphology in minipigs following magnesium treatment was similar to that of the normal bone, whereas an abnormal and concave morphology was displayed following the calcium sulfate treatment. The average bone healing rate for the magnesium-treated defects was higher than that of the calcium sulfate-treated defects at the first 4 months following the implantation. Overall, magnesium treatment appeared to calcium sulfate treatment. Thus, the MAO-coated ZK60 al substitute, and further research on its biological activity in improve the defect repair as compared with the oy appears to be a useful biocompatible bone graft vivo is needed.展开更多
One of the biggest challenges in the biocompatibility of implantable metals is the prevention of the stress shielding effect,which is related to the coupling of the bone-metal mechanical properties.This stress shieldi...One of the biggest challenges in the biocompatibility of implantable metals is the prevention of the stress shielding effect,which is related to the coupling of the bone-metal mechanical properties.This stress shielding phenomenon provokes bone resorption and the consequent adverse effects on prosthesis fixation.However,it can be inhibited by adapting the stiffness of the implant material.Since the use of titanium(Ti)porous structures is a great alternative not only to inhibit this effect but also to improve the osteointegration of orthopedic and dental implants,a brief description of the techniques used for their manufacturing and a review of the current commercialized implants produced from porous Ti assemblies are compiled in this work.As powder metallurgy(PM)with space holder(SH)is a powerful technology used to produce porous Ti structures,it is here discussed its potential for the fabrication of medical devices from the perspectives of both design and manufacture.The most important parameters of the technique such as the size and shape of the initial metallic particles,the SH and binder type of materials,the compaction pressure of the green form,and in the sintering stage,the temperature,atmosphere,and time are reviewed according to the bibliography reported.Furthermore,the importance of the porosity and its types together with the influence of the mentioned parameters in the final porosity and,consequently,in the ultimate mechanical properties of the structure are discussed.Finally,a few examples of the PM-SH application for the manufacturing of orthopedic implants are presented.展开更多
The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus...The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the(molecular)weight loss and the morphological and mechanical variations after immersion in SBF.The in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical methods.Both scaffold parts kept their structural integrity,while changes in morphology were observed,especially for the PLA/G5 scaffold.Mechanical properties decreased with progressive degradation,while the PLA/G5 scaffolds presented higher compressive modulus than PLA scaffolds.The tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds,while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed vascularization.Analysis revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 layers.Altogether,the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical strength.Furthermore,the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs,while within the PLA parts a significantly lower vascularization was found optimally for chondral regeneration.Thus,this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue defects.Additionally,the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one experimental animal.展开更多
Bioglass, with the code name 45S5, contains 45% silica, 24.5% CaO, 24.5% Na2O and 6% P2O5 in weight percent. All of these oxides are mixed together and melted at around 1350℃ to form a homogeneous silica network glas...Bioglass, with the code name 45S5, contains 45% silica, 24.5% CaO, 24.5% Na2O and 6% P2O5 in weight percent. All of these oxides are mixed together and melted at around 1350℃ to form a homogeneous silica network glass.1 Bioglass possesses fast biological response and fast bioactivity, when implanted in living tissue. Since Hench et alI reported over 35 years ago that the bioglass composition could chemically bind to bone,展开更多
Background: Regenerative techniques help promote the formation of new attachment and bone filling in periodontal detects. However, the dimensions of intraosseous defects are a key determinant of periodontal regenerat...Background: Regenerative techniques help promote the formation of new attachment and bone filling in periodontal detects. However, the dimensions of intraosseous defects are a key determinant of periodontal regeneration outcomes. In this study, we evaluated the efficacy of use of anorganic bovine bone (ABB) graft in combination with collagen membrane (CM), to facilitate healing ofnoncontained (1-wall) and contained (3-wall) critical size periodontal defects. Methods: The study began on March 2013, and was completed on May 2014. One-wall (7 mm × 4 mm) and 3-wall (5 mm × 4 mm) intrabony periodontal defects were surgically created bilaterally in the mandibular third premolars and first molars in eight beagles. The defects were treated with ABB in combination with CM (ABB + CM group) or open flap debridement (OFD group). The animals were euthanized at 8-week postsurgery for histological analysis. Two independent Student's t-tests (1-wall [ABB + CM] vs. 1-wall [OFD] and 3-wall [ABB + CM] vs. 3-wall [OFD]) were used to assess between-group differences. Results: The mean new bone height in both 1- and 3-wall intrabony defects in the ABB + CM group was significantly greater than that in the OFD group (1-wall: 4.99± 0.70 mm vs. 3.01 ± 0.37 mm, P 〈 0.05; 3-wall: 3.11±0.59 mm vs. 2.08± 0.24 mm, P 〈 0.05). The mean new cementum in 1-wall intrabony defects in the ABB + CM group was significantly greater than that in their counterparts in the OFD group (5.08 ±0.68 mm vs. 1.16 ± 0.38 mm; P 〈 0.05). Likewise, only the 1-wall intrabony defect model showed a significant difference with respect to junctional epithelium between ABB + CM and OFD groups (0.67 ±0.23 mm vs. 1.12 ± 0.28 mm, P 〈 0.05). Conclusions: One-wall intrabony defects treated with ABB and CM did not show less periodontal regeneration than that in 3-wall intrabony defect. The noncontained l-wall intrabony defect might be a more discriminative defect model for further research into periodontal regeneration.展开更多
Biomineralized collagen composite materials pose an intriguing alternative to current synthetic bone graft substitutes by offering a biomimetic composition that closely resembles native bone.We hypothesize that this c...Biomineralized collagen composite materials pose an intriguing alternative to current synthetic bone graft substitutes by offering a biomimetic composition that closely resembles native bone.We hypothesize that this composite can undergo cellular resorption and remodeling similar to natural bone.We investigate the formation and activity of human osteoclasts cultured on biomineralized collagen and pure collagen membranes in comparison to cortical bone slices.Human monocytes/macrophages from peripheral blood differentiate into multinucleated,tartrate-resistant alkaline phosphatase(TRAP)-positive osteoclast-like cells on all substrates.These cells form clear actin rings on cortical bone,but not on biomineralized collagen or pure collagen membranes.Osteoclasts form resorption pits in cortical bone,resulting in higher calcium ion concentration in cell culture medium;however,osteoclast resorption of biomineralized collagen and collagen membranes does not measurably occur.Activity of osteoclast enzymes-TRAP,carbonic anhydrase II(CA-II),and cathepsin-K(CTS-K)-is similar on all substrates,despite phenotypic differences in actin ring formation and resorption.The mesh-like structure,relatively low stiffness,and lack of RGD-containing binding domains are likely the factors responsible for preventing formation of stable actin rings on and resorption of(biomineralized)collagen membranes.This insight helps to guide further research toward the optimized design of biomineralized collagen composites as a more biomimetic bone-graft substitute.展开更多
文摘Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point CT scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.
基金supported by the investigator-initiated trial "The observation of bone healing after filling with bone grafts of cystic lesions in jaws: a single-center prospective study" at First Affiliated Hospital, School of Medicine, Zhejiang University
文摘BACKGROUND Bone grafts have been applied for many years in orthopedic surgery to assist with bone repair for defects or bone discontinuity caused by trauma and tumors as well as periodontal defects.Jaw cysts are another common benign disease of the maxillofacial region which may lead to pathological bone fracture,loss of teeth,and infection.However,whether bone grafts are beneficial for bone regeneration in jaw cystic lesions and when bone grafts should be used remains unclear.AIM To study the efficacy of bone grafts compared to spontaneous healing in the treatment of jaw cystic lesions.METHODS A literature search was performed in Medline,Cochrane Library and Embase to identify related articles published in English in the last ten years.The following key words and Me SH terms were used:“jaw cyst”,“cystic lesion”,“odontogenic cyst”,“periapical cyst”,“dentigerous cyst”,“follicular cyst”,“keratocyst”,“treatment”,“surgery”,“bone graft”,“enucleation”,“cystectomy”,and“bone regeneration”.Case reports,clinical trials,clinical studies,observational studies and randomized controlled trials were included.Study quality was evaluated.RESULTS Ten studies(n=10)met the inclusion criteria.Five studies reported spontaneous bone healing after enucleation,three studies investigated the efficacy of various bone grafts,and two randomized comparative studies focused on the comparison between spontaneous healing and bone grafting.Over 90%of bone regeneration occurred within 6 mo after bone grafting.The bone regeneration rate after cystectomy showed great variation,ranging from 50%to 100%after 6 mo,but reaching over 90%after 12 mo.CONCLUSION While the long-term superiority of bone grafting compared with spontaneous healing after cystectomy is unclear,bone grafts accelerate the process of healing and significantly increase bone quality.
文摘Purpose: To investigate the periapical tissue response after root end filling with intermediate restorative material (IRM) and filling of the root-end resection bone defects with autogenous bone or a bone graft substitute in comparison to empty controls. Materials and Methods: Vital roots of the second, third and fourth mandibular premolars in six healthy mongrel dogs were apectomized. The root canals were prepared and sealed with IRM following a standardized surgical procedure. The resection bone defects were either filled with autogenous bone (PB) or one of the bone graft substitutes;CERAMENTTM|BONE VOID FILLER, ChronOS?, TigranTM PTG, Easygraft? CLASSIC or left empty. After 120 days the animals were sacrificed and the specimens were analyzed radiologically and histologically. Kruskal-Wallis and Mann-Whitney tests were performed for statistical evaluation. Results: 34 sections were analyzed histologically. The evaluation revealed a variation in the outcome amongst the tested options, regarding reestablishment of the periapical bone healing and inflammatory infiltration in the sections. According to the tested variables, there was no statistical significant difference between the materials when comparing all groups as a whole. When comparing individual materials to each other there was statistical differences among some of the tested materials. Conclusion: The healing outcome after periapical surgery of a five-wall resection defect could not be increased by infill with autogenous bone or bone graft substitutes. The most important factor for the healing outcome in periapical surgery is the quality of the root-end sealing. The healing outcome after some of the tested bone substitutes, might be improved by longer healing time.
基金supported by National Natural Science Foundation of China (31971326)Science and Technology Project of Suzhou (ZXT2022007).
文摘Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair material.Unfortunately,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologic reactions,infection risks,and geometrical mismatching concerns hampered tissue graft use and underscored the need for scaffolds for more effective bone reconstructions due to their tunable properties.Significant progress has been carried out in past decade in the fields of nanoceramics synthesis,bioconjugate chemistry,and composite material processing.This review outlines hierarchical structures and biology of bone tissue,materialistic compo-nents of scaffolds(bioceramics,polymers,bioactive drugs),featured scaffolding strategies(nanofibers,hydrogels,aerogels,bioprinting,and fiber-reinforced composite),and emphasis that hierarchical and physiochemical char-acteristics of bone should be used as an inspiration for scaffold design.This review discussed how differences in materiobiological aspects of scaffolds,such as polymer/bioceramic nanocomposite,mineralized nanocomposite,matrix-rich nanocomposite,3D microenvironmental cues,pore space cues,mechanical cues,usage of physical stimulation(magnetic,electroactive,and photoactivated cues),surface cues(wettability,roughness,textured,and surface charge),and biointerface cues(cell-biomaterial interactions,cell-selective homing,and cell regula-tory strategies)modulate cellular and biological response for bone tissue engineering.This study further outlines the challenges and benefits of integrating materiobiological cues of scaffolds for bone tissue engineering.
文摘Recently, porous titanium granules (PTGs) have been indicated for the preservation of the dimensions of post-extraction sockets, as a filler in sinus lift procedures and for the treatment of peri-implant and periodontal defects, based on the osteoconductivity and dimensional stability of the titanium granules. However, there is a lack of information regarding the use of this material in larger defects and in conjunction with membranes. The objective of this study is to test the behavior of PTGs used to fill critical size defects in rabbit tibiae, with and without membranes. Critical defects were created in both tibiae of rabbits, divided randomly into three groups: Group A (defect filled with PTG), Group B (defect filled with PTG+collagen membrane) and a control group (empty defect). After six weeks, histomorphometric analysis was performed. The results showed more defect closures at the cortical area (87.37%±2.2%) and more bone formation at the marrow area (57.6%± 1.3%) in Group B, in comparison with the other groups (P〈0.05); the use of membranes improved the material stability expressed as more percentages of the original material when membranes were used (P〈0.05). Finally, inflammatory reactions were observed when the granules were not protected by membranes. In spite of the limitations of this animal study, it may be concluded that PTG particles are osteoconductive and allow bone growth. The PTG particles must be covered by a membrane, especially when grafting larger defects, in order to control particle migration, promote clot stabilization and separate the PTG graft from undesired soft tissue cells.
基金Supported by Grant from the shaanxi Provincial Science and Technology Foundation(2000K_(14)-G_(16))
文摘Objective: To prepare hydroxyapatite cement (or calcium phosphate cement, CPC) and analyze its capability. Methods: Tetracalcium phosphate (TTCP) was prepared by the method of high heat. TTCP reacted with in simulated body situation and produced CPC, Its capability was analyzed by scanning electron microscopy (SEM) , X-ray diffraction(XRD). Its density, absorbing water coefficient, macroporosity and campressive strength were measured also. Results: The main element of CPC is hydroxyapatite (HA) , its microstructure comprised of needlelike or petal crystals. The diameter of micropore was 4-10 nm, density was 1.922 g/cm3, macroporosity was 29. 777% , absorbing coefficient was 15. 503%, compressive strength was 42. 70 Mpa. Conclusion: This CPC has three-dimensional spatial structure, its strength meets the need of cancellous bone grafting.
基金Supported by the Jilin Province Science and Technology Development Plan Project,No.20180101123JC13th Five-Year Science and Technology Project of Jilin Provincial Education Department,No.JJKH20190096KJ+2 种基金Jilin Province Health and Health Technology Innovation Project,No.2018J072Project of Jilin Provincial Development and Reform Commission,No.2019C051-2and Jilin Province TCM Science and Technology Project,No.2019036。
文摘BACKGROUND In this case study,a minimally invasive transalveolar approach using platelet-rich fibrin and bone substitute with simultaneous implantation was carried out in an elderly patient.We analyzed the cone-beam computed tomography(CBCT)findings to evaluate bone regeneration.CASE SUMMARY A 65-year-old female with no contraindications for dental implants and loss of maxillary bilateral molars is described.Examination by CBCT showed the available vertical bone height in the bilateral posterior maxilla was 0.5-6.8 mm in the left and 2.8-6.5 mm in the right.The patient underwent a transalveolar approach using platelet-rich fibrin and bone substitute with simulataneous placement of an implant 10 mm in length.Six months post-surgery,the implant showed excellent osseointegration with the bone graft.Thereafter,full-ceramic crowns were fitted.Follow-up at 2 years demonstrated satisfactory prognosis.CONCLUSION Platelet-rich fibrin and bone substitute can be used to augment the maxillary sinus with a vertical bone height less than 4 mm.
基金This work was supported in part by Shenzhen Science and Technology Innovation Funding JCYJ20140414090541811,JCYJ20160429190821781 and JCYJ2016429185449249Hong Kong Research Grant Council General Research Funds(RGC GRF)(Nos.718913E,17214516,N_HKU725/16)+3 种基金HKU Seeding Fund(Nos.201511160001 and 201411159045)Hong Kong Innovation Technology Fund(No.ITS/147/15)Hong Kong Health and Medical Research Fund(No.03142446)National Natural Science Foundation of China(NSFC)(Nos.31370957).
文摘Bone grafts have been predominated used to treat bone defects,delayed union or non-union,and spinal fusion in orthopaedic clinically for a period of time,despite the emergency of synthetic bone graft substitutes.Nevertheless,the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies.Hence,the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important.To address this problem,addition of various growth factors,such as bone morphogenetic proteins(BMPs),parathyroid hormone(PTH)and platelet rich plasma(PRP),into structural allografts and synthetic substitutes have been considered.Although clinical applications of these factors have exhibited good bone formation,their further application was limited due to high cost and potential adverse side effects.Alternatively,bioinorganic ions such as magnesium,strontium and zinc are considered as alternative of osteogenic biological factors.Hence,this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.
文摘This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/ healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.
基金This work was partly supported by National Basic Research Program(973 Program)of China(2011CB606205)‘Twelfth Five-Year’National Science and Technology Support Program(2012BAI17B02)funded by the Ministry of Science and Technology of China,and the National Natural Science Foundation of China(21371106,51402167)Shandong province science and technology development program(2013GGA10036).Conflict of interest statement.None declared.
文摘Revision total hip arthroplasty(THA)with massive bone loss has been a real challenge for orthopaedic surgeons.Here we describe an approach using mineralized collagen(MC)graft to reconstruct acetabulum and femur with massive bone defects.We identified 89 patients suffering acetabular or femoral bone defects after primary THA,who required revision THA for this study.During the surgery,MC was applied to reconstruct both the acetabular and femoral defects.Harris hip score was used to evaluate hip function while radiographs were taken to estimate bone formation in the defect regions.The average follow-up period was 33.662.4 months.None of the components needed re-revised.Mean Harris hip scores were 42.563.5 before operation,75.264.0 at 10th month and 95.063.6 at the final follow-up.There were no instances of deep infection,severe venous thrombosis or nerve palsy.The present study demonstrated that MC graft can serve as a promising option for revision THA with massive bone deficiency.Meanwhile,extended follow-up is needed to further prove its long-term performance.
文摘This study investigated clinical outcomes of biomimetic mineralized collagen artificial bone putty for bone reconstruction in the treatment of calcaneus fracture.Sixty cases of calcaneal fractures surgically treated with open reduction and internal fixation in our hospital from June 2014–2015 were chosen and randomly divided into two groups,including 30 cases treated with biomimetic mineralized collagen artificial bone putty as treatment group,and 30 cases treated with autogenous ilia as control group.The average follow-up time was 17.263.0 months.The results showed that the surgery duration and postoperative drainage volume of treatment group were significantly lower than control group;there were no statistically significant differences in the fracture healing time,American Orthopaedic Foot and Ankle Society scores at 3 and 12 months after surgery,Bo¨hler’s angle,Gissane’s angle and height of calcaneus between the two groups.There were no significant differences in wound complication and reject reaction between the two groups,while significant difference in donor site complication.As a conclusion,the implantation of biomimetic mineralized collagen artificial bone putty in the open reduction of calcaneal fracture resulted in reliable effect and less complications,which is suitable for clinical applications in the treatment of bone defect in calcaneal fractures.
文摘Porous architecture in bone substitutes,notably the interconnectivity of pores,is a critical factor for bone ingrowth.However,controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods,such as sintering.Herein,we fabricated a porous block using the crystal growth of calcium sulfate dihydrate,and controlled the pore interconnectivity by limiting the region of crystal growth.The calcium sulfate dihydrate blocks were transformed to bone apatite,carbonate apatite(CO_(3)Ap)through dissolution–precipitation reactions.Thus,CO_(3)Ap blocks with 15%and 30%interconnected pore volumes were obtained while maintaining the microarchitecture:they were designated as CO_(3)Ap-15 and CO_(3)Ap-30,respectively.At 4 weeks after implantation in a rabbit femur defect,new bone formed throughout CO_(3)Ap-30,whereas little bone was formed in the center region of CO_(3)Ap-15.At 12 weeks after implantation,a large portion of CO_(3)Ap-30 was replaced with new bone and the boundary with the host bone became blurred.In contrast,CO_(3)Ap-15 remained in the defect and the boundary with the host bone was still clear.Thus,the interconnected pores promote bone ingrowth,followed by replacement of the material with new bone.These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.
基金the financial support of National Basic Research Program of China(973 Program,No.2012CB 619101)the National Natural Science Foundation of China (Nos.30970715 and 81101387)
文摘Bone graft substitutes are widely-studied as alternatives to bone grafts in the clinic. The currently available products are mostly ceramics and polymers. Considerable progress has been made in the study of the biodegradable magnesium alloys, which possess the necessary attributions of a suitable substitute, including an excellent mechanical property. In the present study, a minipig model of a lateral tibial plateau defect was used to evaluate the effectiveness of a magnesium alloy in the repair of a critical-sized defect. The micro-arc oxidation (MAO)-coated ZK60 alloy tablets and medical-grade calcium sulfate pellets were used as the test and control materials, respectively. Bone morphology was monitored by computed tomography after the implantation for 2 and 4 months. It was found that the bone morphology in minipigs following magnesium treatment was similar to that of the normal bone, whereas an abnormal and concave morphology was displayed following the calcium sulfate treatment. The average bone healing rate for the magnesium-treated defects was higher than that of the calcium sulfate-treated defects at the first 4 months following the implantation. Overall, magnesium treatment appeared to calcium sulfate treatment. Thus, the MAO-coated ZK60 al substitute, and further research on its biological activity in improve the defect repair as compared with the oy appears to be a useful biocompatible bone graft vivo is needed.
基金the Ministry of Science and Innovation of Spain for financial support(Nos.RTI2018098075-B-C21 and RTI2018-098075-B-C22)the EU through the European Regional Development Funds(No.MINECO-FEDER,EU)+1 种基金Generalitat de Catalunya(No.2017SGR-1165)the KTT Excellence Program,funded by the European Union through the European Regional Development Fund(EDF),the Government of Catalonia and the UPC。
文摘One of the biggest challenges in the biocompatibility of implantable metals is the prevention of the stress shielding effect,which is related to the coupling of the bone-metal mechanical properties.This stress shielding phenomenon provokes bone resorption and the consequent adverse effects on prosthesis fixation.However,it can be inhibited by adapting the stiffness of the implant material.Since the use of titanium(Ti)porous structures is a great alternative not only to inhibit this effect but also to improve the osteointegration of orthopedic and dental implants,a brief description of the techniques used for their manufacturing and a review of the current commercialized implants produced from porous Ti assemblies are compiled in this work.As powder metallurgy(PM)with space holder(SH)is a powerful technology used to produce porous Ti structures,it is here discussed its potential for the fabrication of medical devices from the perspectives of both design and manufacture.The most important parameters of the technique such as the size and shape of the initial metallic particles,the SH and binder type of materials,the compaction pressure of the green form,and in the sintering stage,the temperature,atmosphere,and time are reviewed according to the bibliography reported.Furthermore,the importance of the porosity and its types together with the influence of the mentioned parameters in the final porosity and,consequently,in the ultimate mechanical properties of the structure are discussed.Finally,a few examples of the PM-SH application for the manufacturing of orthopedic implants are presented.
基金We thank the Spanish MINECO for supporting the project MAT2012-38793 and for funding MN through the Ramon y Cajal program and TS through the“Personal Tecnico de Apoyo”subprogram.
文摘The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the(molecular)weight loss and the morphological and mechanical variations after immersion in SBF.The in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical methods.Both scaffold parts kept their structural integrity,while changes in morphology were observed,especially for the PLA/G5 scaffold.Mechanical properties decreased with progressive degradation,while the PLA/G5 scaffolds presented higher compressive modulus than PLA scaffolds.The tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds,while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed vascularization.Analysis revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 layers.Altogether,the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical strength.Furthermore,the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs,while within the PLA parts a significantly lower vascularization was found optimally for chondral regeneration.Thus,this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue defects.Additionally,the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one experimental animal.
文摘Bioglass, with the code name 45S5, contains 45% silica, 24.5% CaO, 24.5% Na2O and 6% P2O5 in weight percent. All of these oxides are mixed together and melted at around 1350℃ to form a homogeneous silica network glass.1 Bioglass possesses fast biological response and fast bioactivity, when implanted in living tissue. Since Hench et alI reported over 35 years ago that the bioglass composition could chemically bind to bone,
文摘Background: Regenerative techniques help promote the formation of new attachment and bone filling in periodontal detects. However, the dimensions of intraosseous defects are a key determinant of periodontal regeneration outcomes. In this study, we evaluated the efficacy of use of anorganic bovine bone (ABB) graft in combination with collagen membrane (CM), to facilitate healing ofnoncontained (1-wall) and contained (3-wall) critical size periodontal defects. Methods: The study began on March 2013, and was completed on May 2014. One-wall (7 mm × 4 mm) and 3-wall (5 mm × 4 mm) intrabony periodontal defects were surgically created bilaterally in the mandibular third premolars and first molars in eight beagles. The defects were treated with ABB in combination with CM (ABB + CM group) or open flap debridement (OFD group). The animals were euthanized at 8-week postsurgery for histological analysis. Two independent Student's t-tests (1-wall [ABB + CM] vs. 1-wall [OFD] and 3-wall [ABB + CM] vs. 3-wall [OFD]) were used to assess between-group differences. Results: The mean new bone height in both 1- and 3-wall intrabony defects in the ABB + CM group was significantly greater than that in the OFD group (1-wall: 4.99± 0.70 mm vs. 3.01 ± 0.37 mm, P 〈 0.05; 3-wall: 3.11±0.59 mm vs. 2.08± 0.24 mm, P 〈 0.05). The mean new cementum in 1-wall intrabony defects in the ABB + CM group was significantly greater than that in their counterparts in the OFD group (5.08 ±0.68 mm vs. 1.16 ± 0.38 mm; P 〈 0.05). Likewise, only the 1-wall intrabony defect model showed a significant difference with respect to junctional epithelium between ABB + CM and OFD groups (0.67 ±0.23 mm vs. 1.12 ± 0.28 mm, P 〈 0.05). Conclusions: One-wall intrabony defects treated with ABB and CM did not show less periodontal regeneration than that in 3-wall intrabony defect. The noncontained l-wall intrabony defect might be a more discriminative defect model for further research into periodontal regeneration.
基金the support of the Dutch Province of Limburg(LINK project)the Gravitation Program‘Materials-Driven Regeneration’,funded by the Netherlands Organisation for Scientific Research(NWO).
文摘Biomineralized collagen composite materials pose an intriguing alternative to current synthetic bone graft substitutes by offering a biomimetic composition that closely resembles native bone.We hypothesize that this composite can undergo cellular resorption and remodeling similar to natural bone.We investigate the formation and activity of human osteoclasts cultured on biomineralized collagen and pure collagen membranes in comparison to cortical bone slices.Human monocytes/macrophages from peripheral blood differentiate into multinucleated,tartrate-resistant alkaline phosphatase(TRAP)-positive osteoclast-like cells on all substrates.These cells form clear actin rings on cortical bone,but not on biomineralized collagen or pure collagen membranes.Osteoclasts form resorption pits in cortical bone,resulting in higher calcium ion concentration in cell culture medium;however,osteoclast resorption of biomineralized collagen and collagen membranes does not measurably occur.Activity of osteoclast enzymes-TRAP,carbonic anhydrase II(CA-II),and cathepsin-K(CTS-K)-is similar on all substrates,despite phenotypic differences in actin ring formation and resorption.The mesh-like structure,relatively low stiffness,and lack of RGD-containing binding domains are likely the factors responsible for preventing formation of stable actin rings on and resorption of(biomineralized)collagen membranes.This insight helps to guide further research toward the optimized design of biomineralized collagen composites as a more biomimetic bone-graft substitute.