Hierarchical porous structure,which include macropores,minor pores,and micropores in scaffolds,are essential in the multiple biological functions of bone repair and regeneration.In this study,patientcustomized calcium...Hierarchical porous structure,which include macropores,minor pores,and micropores in scaffolds,are essential in the multiple biological functions of bone repair and regeneration.In this study,patientcustomized calcium-deficient hydroxyapatite(CDHA)scaffolds with three-level hierarchical porous structure were fabricated by indirect 3D printing technology and particulate leaching method.The sacrificial template scaffolds were fabricated using a photo-curing 3D printer,which provided a prerequisite for the integral structure and interconnected macropores of CDHA scaffolds.Additionally,20 wt%pore former was incorporated into the slurry to enhance the content of smaller pores within the CDHA-2 scaffolds,and then the CDHA-2 scaffolds were sintered to remove the sacrificial template scaffolds and pore former.The obtained CDHA-2 scaffolds exhibited interconnected macropores(300-400μm),minor pores(∼10-100μm),and micropores(<10μm)distributed throughout the scaffolds,which could promote bone tissue ingrowth,increase surface roughness,and enhance protein adsorption of scaffolds.In vitro studies identified that CDHA-2 scaffolds had nanocrystal grains,high specific surface area,and outstanding protein adsorption capacity,which could provide a microenvironment for cell adhesion,spreading,and proliferation.In addition,the murine intramuscular implantation experiment suggested that CDHA-2 scaffolds exhibited excellent osteoinductivity and were superior to traditional BCP ceramics under conditions without the addition of live cells and exogenous growth factors.The rabbit calvarial defect repair results indicated that CDHA-2 scaffolds could enhance in situ bone regeneration.In conclusion,these findings demonstrated that the hierarchical porous structure of CDHA scaffolds was a pivotal factor in modulating osteoinductivity and bone regeneration,and CDHA-2 scaffolds were potential candidates for bone regeneration.展开更多
Recent studies have indicated that demineralized cortical bone(DCB)may be used to repair tendons and ligaments,such as the patellar tendon and anterior cruciate ligament(ACL).Hydrogen peroxide(H_(2)O_(2))has been show...Recent studies have indicated that demineralized cortical bone(DCB)may be used to repair tendons and ligaments,such as the patellar tendon and anterior cruciate ligament(ACL).Hydrogen peroxide(H_(2)O_(2))has been shown to reduce the osteoinductivity of DCB,and heat treatment may also decrease the osteoinductivity of DCB.The purpose of this study was(i)to determine whether heat treat-ment reduces the osteoinductivity of DCB and(ii)to compare the effectiveness of heat treatment and H_(2)O_(2)treatment on BMP-2 in-activation.DCB was prepared by immersion in 0.6 N hydrochloric acid,and DCB-H and DCB-HO were prepared by heat treatment(70�C for 8 h)and H_(2)O_(2)treatment(3%H_(2)O_(2)for 8 h),respectively.The surface topographies,elemental distributions and histological structures of the scaffolds were observed by scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FT-IR)and histological staining.The viability and osteogenic differentiation of TDSCs cultured on the scaffolds were evaluated via live/dead cell staining and Cell Counting Kit-8(CCK-8)testing,real-time polymerase chain reaction(RT-PCR)and western bolt(WB)analysis,alkaline phosphatase activity(ALP)and alizarin red S(ARS)staining.The intramuscular implantation of the scaffolds in rats was also used to evaluate the effect of heat treatment and H_(2)O_(2)treatment on the osteoinductivity of DCB.Our results demonstrated that both treatments removed BMP-2 and osteocalcin(OCN)within the DCB and that DCB-H and DCB-HO had good cytocompatibility and reduced the osteo-genic differentiation of TDSCs.Moreover,the in vivo results indicated that the DCB-H and DCB-HO groups had smaller areas of osteoid formation than did the DCB group,and the DCB-HO group had the smallest area among the three groups.Our study demonstrated that heat treatment could reduce the osteoinductivity of DCB,and that H_(2)O_(2)treatment was more effective than heat treatment.展开更多
With the increase of global population,people’s life expectancy is growing as well.Humans tend to live more active lifestyles and,therefore,trauma generated large defects become more common.Instances of tumour resect...With the increase of global population,people’s life expectancy is growing as well.Humans tend to live more active lifestyles and,therefore,trauma generated large defects become more common.Instances of tumour resection or pathological conditions and complex orthopaedic issues occur more frequently increasing necessity for bone substitutes.Composition of calcium phosphate cements(CPCs)is comparable to the chemical structure of bone minerals.Their ability to self-set and resorb in vivo secures a variety of potential applications in bone regeneration.Despite the years-long research and several products already reaching the market,finding the right properties for calcium phosphate cement to be osteoinductive and both injectable and suitable for clinical use is still a sudoku.This article is focused on injectable,porous CPCs,reviewing the latest developments on the path toward finding osteoinductive material,which is suitable for injection.展开更多
Surface modification using bioactive molecules is frequently performed to improve the biological properties of medical metal biomaterial titanium(Ti)implants.Developmental evidence suggests that mesenchymal stem cell-...Surface modification using bioactive molecules is frequently performed to improve the biological properties of medical metal biomaterial titanium(Ti)implants.Developmental evidence suggests that mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)served as potent bioactive component.As a subset of MSC EV,adipose-derived stem cel-derived extracellular vesicles(ADSC-EVs)could be obtained from abundant adipose tissue.Meanwhile,it possesses multiple re-generative properties and might be used to endow biological activities to medical Ti implant.Here,we present a simple ADSC-EV coating strategy based on physisorption of fibronectin.This ADSC-EV functionalized Ti implants(EV-Ti)revealed enhanced osteoblast compatibility and osteoinduc-tive activity.Cell spreading area of EV-Ti group was 1.62-and 1.48-fold larger than that of Ti group after 6 and 12 h of cell seeding,respectively.Moreover,EV-Ti promoted alkaline phosphatase,col-lagen 1 and osteocalcin gene expression in osteoblast by 1.51-,1.68-and 1.82-fold compared with pristine Ti,respectively.Thus,the MSC-EVs modification method reported here provide a clinically translatable strategy to promote the bioactivity of Ti implants.展开更多
The increasing recognition of the contribution of the immune system to activate and prime regeneration implies that tissue engineering strategies and biomaterials design should target regulation of early immunological...The increasing recognition of the contribution of the immune system to activate and prime regeneration implies that tissue engineering strategies and biomaterials design should target regulation of early immunological processes.We previously proposed the cell-based engineering and devitalization of extracellular matrices(ECMs)as a strategy to generate implant materials delivering custom-defined signals.Here,in the context of bone regeneration,we aimed at enhancing the osteoinductivity of such ECMs by enriching their immunomodulatory factors repertoire.Priming with IL1βa cell line overexpressing BMP-2 enabled engineering of ECMs preserving osteoinductive signals and containing larger amounts of angiogenic(VEGF)and pro-inflammatory molecules(IL6,IL8 and MCP1).Upon implantation,these IL1β-induced materials enhanced processes typical of the inflammatory phase(e.g.,vascular invasion,osteoclast recruitment and differentiation),leading to‘regenerative’events(e.g.,M2 macrophage polarization)and ultimately resulting in faster and more efficient bone formation.These results bear relevance towards the manufacturing of potent off-the-shelf osteoinductive materials and outline the broader paradigm of engineering immunoinstructive implants to enhance tissue regeneration.展开更多
A layer of porous film containing Ca and P was prepared by the micro-arc oxidation method on the surface of a novel near β biomedical Ti-3Zr-2Sn-3Mo-25Nb alloy, and then NH2- active group was introduced to the films ...A layer of porous film containing Ca and P was prepared by the micro-arc oxidation method on the surface of a novel near β biomedical Ti-3Zr-2Sn-3Mo-25Nb alloy, and then NH2- active group was introduced to the films by activation treatment. The phase composition, surface micro-topography and elemental characteristics of the micro-arc oxidation films were investigated with XRD, SEM, EDS and XPS, and the osteoinduction of the micro-arc oxidation films was tested using the simulated body fluid immersion, the in-vitro osteoblast cultivation test and animal experiment. The results show that the oxide layer is a kind of porous ceramic intermixture and contains Ca and P. The films in the simulated body fluid can induce apatite formation, resulting in excellent bioactivity. The cell test discovers that osteoblasts can grow well on the surface of micro-arc oxidation films. And the Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy coated with active porous calcium-phosphate films shows better osteoinduction in vivo.展开更多
How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelit...How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelitis.The present study introduced a novel one-step route to realizing the co-doping of zinc oxide(ZnO)and zinc ion(Zn^(2+))in biphasic calcium phosphate(BCP)ceramics to utilize their synergistic antibacterial.Compared with the conventional BCP ceramics(BCP-Ca),the ZnO/Zn^(2+)co-doping ones(BCP-Zn)possessed strong antibacterial ability on E.coli and S.aureus as well as stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)effectively.The synergistic antibacterial mechanism of ZnO and Zn^(2+)was also investigated.BCP-Zn showed excellent osteoinductivity and angiogenesis at three months postoperatively in the canine intramuscular implantation model.Moreover,BCP-Zn exhibited excellent anti-infective ability and bone regenerative repair compared to BCP-Ca and control groups in the infected bone defect model of rat femur.Collectively,these findings suggest that the simultaneous introduction of ZnO/Zn^(2+)could have immense potential to expand the application of osteoinductive BCP ceramics in the regenerative repair of infected bone defects.展开更多
To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 （BMP2）, biodegradable collagen scaffolds （CS） were used to load BMP-2-derived pep...To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 （BMP2）, biodegradable collagen scaffolds （CS） were used to load BMP-2-derived peptide solutions with different concentrations （0.4 mg peptide/CS, 0.1 mg peptide/CS and pure CS, respectively）, and the implants were implanted into muscular pockets on the back of Wistar rats. Radiographs and histological analysis were performed to evaluate the ectopic bone effects. Active ectopic bone formation was seen in both groups containing the peptide at different concentration （0.4 mg and 0.1 mg）, whereas no bone formation and only fibrous tissue was seen in the pure CS group. The new bone formation induced by the peptide P24 displayed a dose-dependent and time-dependent efficiency. The new bone formation in the 0.4 mg peptide/CS group significantly increased than that of the 0.1 mg peptide/CS group. This novel BMP-2-derived peptide had excellent osteoinductive and ectopicly osteogenic properties which were similar to those of BMP2.展开更多
Additive manufacturing of porous, open-cellular metal or alloy implants, fabricated by laser or electron beam melting of a powder bed, is briefly reviewed in relation to optimizing biomechanical compatibility by assur...Additive manufacturing of porous, open-cellular metal or alloy implants, fabricated by laser or electron beam melting of a powder bed, is briefly reviewed in relation to optimizing biomechanical compatibility by assuring elastic(Young's) modulus matching of proximate bone, along with corresponding pore sizes assuring osseointegration and vasculature development and migration. In addition, associated, requisite compressive and fatigue strengths for such implants are described. Strategies for optimizing osteoblast(bone cell) development and osteoinduction as well as vascularization of tissue in 3 D scaffolds and tissue engineering constructs for bone repair are reviewed in relation to the biology of osteogenesis and neovascularization in bone, and the role of associated growth factors, bone morphogenic proteins, signaling molecules and the like. Prospects for infusing hydrogel/collagen matrices containing these cellular and protein components or surgically extracted intramedullary(bone marrow) concentrate/aspirate containing these biological and cell components into porous implants are discussed, as strategies for creating living implants, which over the long term would act as metal or alloy scaffolds.展开更多
This study examined the biological response of two porous calcium phosphate ceramics, hydroxyapntite （ HA ） and hydroxyapaptite/β-tricalcium phosphate （ HA/β- TCP ） scaffolds. Three different cell types , a huma...This study examined the biological response of two porous calcium phosphate ceramics, hydroxyapntite （ HA ） and hydroxyapaptite/β-tricalcium phosphate （ HA/β- TCP ） scaffolds. Three different cell types , a human osteoblastic cell line （ HOS ） , primary human osteoblasts （HOB） and human mesenehymal stem cells （MSCs）, were used to examine biocompatibility and osteoinductive capacity. The experimental results showed both materials were highly biocompatible and proliferation was significantly greater on pure HA （ P 〈 0.01 ）, with a peak in proliferation at day 7. Protein levels were significantly higher （ P 〈 0.05） than the control Thermanox（ TMX （ tm） ） for both test materials. Osteoinduction of MSCs was observed on both test materials, with cells seeded on HA/ β-TCP showing greater alkaline phosphatase activity compared to HA alone, indicating an enhancement in osteoinductive property. Both materials show good potential for use as tissue engineered scaffolds.展开更多
To improve the osteogenesis ability of a-tricalcium phosphate (α-TCP) bone cement, a novel BMP/ α-TCP composite bone cement was prepared. By measuring the setting time and compressive strength, the hydration charact...To improve the osteogenesis ability of a-tricalcium phosphate (α-TCP) bone cement, a novel BMP/ α-TCP composite bone cement was prepared. By measuring the setting time and compressive strength, the hydration characteristic of bone cement was evaluated. Animal experiments including histological observation, radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,a-TCP bone cement and BMP/α-TCP composite bone cement. Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property. Comparison experiments show that BMP/ α-TCP composite bone cement has a stronger osteogenesis ability. The gross observation of the implant site does not exhibit any inflammation or necrosis. Histological analyses reveal that the material has good osteointegration with host bone, and new bone formation is detected within the materials, which are degrading. Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation. Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement. This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability. Key words α-tricalcium phosphate (α-TCP) - bone morphogenetic proteins (BMP) - bone cement - osteogenesis - osteoinductivity - bone tissue engineering Funded by 863 Hi-Tech Research and Development Program of China (2002AA326080) and the Fund for Outstanding Young Teacher of the Education Ministry of China(2002123)展开更多
The arginine-glycine-aspartic （RGD） acid peptide was grafted to the surface of apatitewollastonite （AW） ceramic in an effort to improve its cell adhesion, proliferation and osteoinduction. RGD peptide was covalent...The arginine-glycine-aspartic （RGD） acid peptide was grafted to the surface of apatitewollastonite （AW） ceramic in an effort to improve its cell adhesion, proliferation and osteoinduction. RGD peptide was covalently immobilized onto the surface of AW ceramic via the synthetic cross linker AA.PTS-E and 1-ethyl-3-（3-dimethylaminopropyl）carbodiimide （EDC）. The modified surfaces were characterized by attenuated total reflectance Fourier transform infrared spectroscopy （ATR-FTIR） and X-ray photoelectron spectroscopy （XPS）. The chemical analysis indicated that RGD peptide had been immobilized onto the AW surface successfully. The growth of osteoblast-like cells （MG63） showed that modifying the AW surface with RGD peptide enhanced the cell adhesion and proliferation. And the histological evaluation of RGD-AW showed that the bone regeneration and remodeling process were significantly enhanced compared to the original AW ceramics after 2, 4 and 8 weeks implantation in rabbit＇s femoral condyles.展开更多
To develop a novel degradable poly (L-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) bioactive materials for bone tissueengineering, β-TCP powder was produced by a new wet process. Porous scaffolds were prepared ...To develop a novel degradable poly (L-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) bioactive materials for bone tissueengineering, β-TCP powder was produced by a new wet process. Porous scaffolds were prepared by three steps, i.e. solventcasting, compression molding and leaching stage. Factors influencing the compressive strength and the degradation behaviorof the porous scaffold, e.g. weight fraction of pore forming agent-sodium chloride (NaCl), weight ratio of PLLA: β-TCP,the particle size of β-TCP and the porosity, were discussed in details. Rat marrow stromal cells (RMSC) were incorporatedinto the composite by tissue engineering approach. Biological and osteogenesis potential of the composite scaffold weredetermined with MTT assay, alkaline phosphatase (ALP) activity and bone osteocalcin (OCN) content evaluation. Resultsshow that PLLA/β-TCP bioactive porous scaffold has good mechanical and pore structure with adjustable compressive strengthneeded for surgery. RMSCs seeding on porous PLLA/β-TCP composite behaves good seeding efficacy, biocompatibility andosteoinductive potential. Osteoprogenitor cells could well penetrate into the material matrix and begin cell proliferation andosteogenic differentiation. Osseous matrix could be formed on the surface of the composite after culturing in vitro. It isexpected that the PLLA/β-TCP porous composites are promising scaffolds for bone tissue engineering in prosthesis surgery.展开更多
AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7(rhB MP-7) for the treatment of nonunions.METHODS Bone morphogenetic proteins(BMPs) promote bone ...AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7(rhB MP-7) for the treatment of nonunions.METHODS Bone morphogenetic proteins(BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients(80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent jointswere also carried out. Factors related to the patient(age, gender), the nonunion(location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure(graft and fixation type, amount of rhB MP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ~2 test was performed.RESULTS Eighty point nine percent of the nonunions treated with rh BMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients(17.8%) and it was apparent in the routine radiologi-cal evaluation of the nonunion site, in a mean time of 5.5 mo after the rh BMP-7 application(range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhB MP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient's gender was the only important factor for the development of heterotopic ossification(P = 0.007). CONCLUSION Heterotopic ossification after the use of rh BMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.展开更多
The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented,but little research has been performed on rodent animals,e.g.,mice.In this study,we report osteoinduction ...The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented,but little research has been performed on rodent animals,e.g.,mice.In this study,we report osteoinduction in a mouse model.Thirty mice were divided into two groups.BCP materials (Sample A) and control ceramics (Sample B) were implanted into the leg muscle,respectively.Five mice in each group were killed at 15,30,and 45 d after surgery.Sample A and Sample B were harvested and used for hematoxylin and eosin (HE) staining,immunohistochemistry (IHC) staining,and Alizarin Red S staining to check bone formation in the biomaterials.Histological analysis showed that no bone tissue was formed 15 d after implantation (0/5) in either of the two groups.Newly-formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after implantation;the average amounts of newly-formed bone tissues were approximately 5.2% and 8.6%,respectively.However,we did not see any bone tissue in Sample B until 45 d after implantation.Bone-related molecular makers such as bone morphogenesis protein-2 (BMP-2),collagen type I,and osteopontin were detected by IHC staining in Sample A 30 d after implantation.In addition,the newly-formed bone was also confirmed by Alizarin Red S staining.Because this is the report of osteoinduction in the rodent animal on which all the biotechnologies were available,our results may contribute to further mechanism research.展开更多
Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self...Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self-healing nano hybrid hydrogel was on-demand prepared via a fast(within 30 s)and easy gelation approach by reversible Schiff base formed between-CH=O of oxidized sodium alginate(OSA)and-NH2 of glycol chitosan(GCS)mixed with calcium phosphate nanoparticles(CaP NPs).Its raw materials can be ready in large quantities by a simple synthesis process.The mechanical strength,degradation and swelling behavior of the hydrogel can be readily controlled by simply controlling the molar ratio of-CH=O and-NH2.This hydrogel exhibits pH responsiveness,good degradability and biocompatibility.The hydrogel used as the matrix for mesenchymal stem cells can significantly induce the proliferation,differentiation and osteoinduction in vitro.These results showed this novel hydrogel is an ideal candidate for applications in bone tissue regeneration and drug delivery.展开更多
The immune response of a biomaterial determines its osteoinductive effect.Although the mechanisms by which some immune cells promote regeneration have been revealed,the biomaterial-induced immune response is a dynamic...The immune response of a biomaterial determines its osteoinductive effect.Although the mechanisms by which some immune cells promote regeneration have been revealed,the biomaterial-induced immune response is a dynamic process involving multiple cells.Currently,it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials.Herein,we investigated the roles of macrophages and dendritic cells(DCs)during the osteoinduction of biphasic calcium phosphate(BCP)scaffolds.We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation,resulting in low T cell response and efficient osteogenesis.Accordingly,a dual-targeting nano-in-micro scaffold(BCP loaded with gold nanocage,BCP-GNC)was designed to regulate the immune responses of macrophages and DCs.Through a dual-wavelength photosensitive switch,BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs,creating a desirable inflammatory environment for osteogenesis.This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.展开更多
HA/TCP and HA rods （φ5 mm×10 mm） were made for implantation in New Zealand white rabbit with different condition. Sixty three rabbit were divided into three groups： group 1 （n=18）, group 2 （n=27） and grou...HA/TCP and HA rods （φ5 mm×10 mm） were made for implantation in New Zealand white rabbit with different condition. Sixty three rabbit were divided into three groups： group 1 （n=18）, group 2 （n=27） and group 3 （n=18）. In group 1, 10 mm radius was defected, and one HA/TCP rod was implanted in the muscle a distant away from the bone defect area. In group 2, also, 10 mm radius was defected, one HA rod was implanted in the muscle a distant away from the bone defect area. In group 3, two HA/TCP rods were implanted in the dorsal muscle of the rabbit with bone intact. Histological observation showed that in group 1, some new bone was found only two months after implantation （n=2）, and obvious immature woven bone could be observed in these bioceramics from the 3rd month on. However, in group 3, bone began to be found 6 months after implantation （n=2）. In group 2, we could not find any bone tissue up to 9 month’s observation. These results suggest that, first, the bone defect model could significantly accelerate bone formation at non-osseous sites in rabbits; second,. HA/TCP bioceramics were confirmed with osteoinductive property while HA bioceramics without osteoinductive property nearly. Thus, bone defect might be a good animal model for further researches for osteoinductive bioceramics.展开更多
This paper reports the results of 24 cases of bone defect resulting from bone tumor or tumor condition excision, and of posterior spinal fusion, treated by human bone matrix gelatin. The success rate of bone defect re...This paper reports the results of 24 cases of bone defect resulting from bone tumor or tumor condition excision, and of posterior spinal fusion, treated by human bone matrix gelatin. The success rate of bone defect repair and spinal fusion is 91. 67 %. The results suggest that human bone matrix gelatin has. excellent osteoinductive effect and is ideal substitute for bone autografts.展开更多
Porous β-tricalcium phosphate (TCP) displays osteoinductivity in certain animals in the absence of osteoinductive agents. We evaluated whether the microstructure may be an important determinant of osteoinduction, and...Porous β-tricalcium phosphate (TCP) displays osteoinductivity in certain animals in the absence of osteoinductive agents. We evaluated whether the microstructure may be an important determinant of osteoinduction, and also investigated how bone formation was promoted using β-TCP combined with bone marrow aspirates. We prepared two types of β-TCP, namely, β-TCP A, which possessed interconnected macropores and micropores, and β-TCP B, which possessed macropores but had less detectable micropores. These were implanted with or without marrow in canine muscles. Bone formation and the resorption of each β-TCP implant were evaluated histologically. Newly formed bone began to appear at day 42 in the implants of β-TCP A alone, but the implants of β-TCP B alone did not show any bone formation by day 42. Meanwhile, bone formation was already evident on day 14 by loading with bone marrow aspirates with or without micropores. By immunohistochemistry, the number of cathepsin K-positive cells (osteoclasts) increased as time passed in the implants of β-TCP A alone, while the number of the osteoclasts did not change obviously in the implants of β-TCP B alone from day 14 to 56. Reticular fibrils were evident within the β-TCP A, and were barely observed in the β-TCP B in the silver impregnation. The present result would bring about the possible role to enhance the importance of the surface microstructure for the better osteoinductivity. Our findings suggest that the combination of porous β-TCP and bone marrow facilitates bone formation.展开更多
基金supported by the National Key Research and Development Program of China(No.2019YFA0110600)the Science and Technology Support Program of Sichuan Province(No.2019YJ0161).
文摘Hierarchical porous structure,which include macropores,minor pores,and micropores in scaffolds,are essential in the multiple biological functions of bone repair and regeneration.In this study,patientcustomized calcium-deficient hydroxyapatite(CDHA)scaffolds with three-level hierarchical porous structure were fabricated by indirect 3D printing technology and particulate leaching method.The sacrificial template scaffolds were fabricated using a photo-curing 3D printer,which provided a prerequisite for the integral structure and interconnected macropores of CDHA scaffolds.Additionally,20 wt%pore former was incorporated into the slurry to enhance the content of smaller pores within the CDHA-2 scaffolds,and then the CDHA-2 scaffolds were sintered to remove the sacrificial template scaffolds and pore former.The obtained CDHA-2 scaffolds exhibited interconnected macropores(300-400μm),minor pores(∼10-100μm),and micropores(<10μm)distributed throughout the scaffolds,which could promote bone tissue ingrowth,increase surface roughness,and enhance protein adsorption of scaffolds.In vitro studies identified that CDHA-2 scaffolds had nanocrystal grains,high specific surface area,and outstanding protein adsorption capacity,which could provide a microenvironment for cell adhesion,spreading,and proliferation.In addition,the murine intramuscular implantation experiment suggested that CDHA-2 scaffolds exhibited excellent osteoinductivity and were superior to traditional BCP ceramics under conditions without the addition of live cells and exogenous growth factors.The rabbit calvarial defect repair results indicated that CDHA-2 scaffolds could enhance in situ bone regeneration.In conclusion,these findings demonstrated that the hierarchical porous structure of CDHA scaffolds was a pivotal factor in modulating osteoinductivity and bone regeneration,and CDHA-2 scaffolds were potential candidates for bone regeneration.
基金supported by grants from the National Natural Science Foundation of China(32171349)Shukun He thanks the China Scholarship Council(CSC)(No.201906240083)Zhejiang Provincial Natural Science Foundation of China under Grant(No.LQ23H060005)for financial support.
文摘Recent studies have indicated that demineralized cortical bone(DCB)may be used to repair tendons and ligaments,such as the patellar tendon and anterior cruciate ligament(ACL).Hydrogen peroxide(H_(2)O_(2))has been shown to reduce the osteoinductivity of DCB,and heat treatment may also decrease the osteoinductivity of DCB.The purpose of this study was(i)to determine whether heat treat-ment reduces the osteoinductivity of DCB and(ii)to compare the effectiveness of heat treatment and H_(2)O_(2)treatment on BMP-2 in-activation.DCB was prepared by immersion in 0.6 N hydrochloric acid,and DCB-H and DCB-HO were prepared by heat treatment(70�C for 8 h)and H_(2)O_(2)treatment(3%H_(2)O_(2)for 8 h),respectively.The surface topographies,elemental distributions and histological structures of the scaffolds were observed by scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FT-IR)and histological staining.The viability and osteogenic differentiation of TDSCs cultured on the scaffolds were evaluated via live/dead cell staining and Cell Counting Kit-8(CCK-8)testing,real-time polymerase chain reaction(RT-PCR)and western bolt(WB)analysis,alkaline phosphatase activity(ALP)and alizarin red S(ARS)staining.The intramuscular implantation of the scaffolds in rats was also used to evaluate the effect of heat treatment and H_(2)O_(2)treatment on the osteoinductivity of DCB.Our results demonstrated that both treatments removed BMP-2 and osteocalcin(OCN)within the DCB and that DCB-H and DCB-HO had good cytocompatibility and reduced the osteo-genic differentiation of TDSCs.Moreover,the in vivo results indicated that the DCB-H and DCB-HO groups had smaller areas of osteoid formation than did the DCB group,and the DCB-HO group had the smallest area among the three groups.Our study demonstrated that heat treatment could reduce the osteoinductivity of DCB,and that H_(2)O_(2)treatment was more effective than heat treatment.
基金The authors acknowledge financial support for granting Open Access from the European Union’s Horizon 2020 research and innovation programme under the grant agreement No.857287.
文摘With the increase of global population,people’s life expectancy is growing as well.Humans tend to live more active lifestyles and,therefore,trauma generated large defects become more common.Instances of tumour resection or pathological conditions and complex orthopaedic issues occur more frequently increasing necessity for bone substitutes.Composition of calcium phosphate cements(CPCs)is comparable to the chemical structure of bone minerals.Their ability to self-set and resorb in vivo secures a variety of potential applications in bone regeneration.Despite the years-long research and several products already reaching the market,finding the right properties for calcium phosphate cement to be osteoinductive and both injectable and suitable for clinical use is still a sudoku.This article is focused on injectable,porous CPCs,reviewing the latest developments on the path toward finding osteoinductive material,which is suitable for injection.
基金This work was supported by the National Key R&D Program of China(2019YFA0110500)the National Natural Science Foundation of China(No.81873941,81701922 and 81701912).
文摘Surface modification using bioactive molecules is frequently performed to improve the biological properties of medical metal biomaterial titanium(Ti)implants.Developmental evidence suggests that mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)served as potent bioactive component.As a subset of MSC EV,adipose-derived stem cel-derived extracellular vesicles(ADSC-EVs)could be obtained from abundant adipose tissue.Meanwhile,it possesses multiple re-generative properties and might be used to endow biological activities to medical Ti implant.Here,we present a simple ADSC-EV coating strategy based on physisorption of fibronectin.This ADSC-EV functionalized Ti implants(EV-Ti)revealed enhanced osteoblast compatibility and osteoinduc-tive activity.Cell spreading area of EV-Ti group was 1.62-and 1.48-fold larger than that of Ti group after 6 and 12 h of cell seeding,respectively.Moreover,EV-Ti promoted alkaline phosphatase,col-lagen 1 and osteocalcin gene expression in osteoblast by 1.51-,1.68-and 1.82-fold compared with pristine Ti,respectively.Thus,the MSC-EVs modification method reported here provide a clinically translatable strategy to promote the bioactivity of Ti implants.
基金supported by the Swiss National Science Foundation Div 3(Grant 31003A-179259 to I.M.)the National Centre of Competence in Research(NCCR)Molecular Systems Engineering(Grant 51NF40-141825 to I.M.).
文摘The increasing recognition of the contribution of the immune system to activate and prime regeneration implies that tissue engineering strategies and biomaterials design should target regulation of early immunological processes.We previously proposed the cell-based engineering and devitalization of extracellular matrices(ECMs)as a strategy to generate implant materials delivering custom-defined signals.Here,in the context of bone regeneration,we aimed at enhancing the osteoinductivity of such ECMs by enriching their immunomodulatory factors repertoire.Priming with IL1βa cell line overexpressing BMP-2 enabled engineering of ECMs preserving osteoinductive signals and containing larger amounts of angiogenic(VEGF)and pro-inflammatory molecules(IL6,IL8 and MCP1).Upon implantation,these IL1β-induced materials enhanced processes typical of the inflammatory phase(e.g.,vascular invasion,osteoclast recruitment and differentiation),leading to‘regenerative’events(e.g.,M2 macrophage polarization)and ultimately resulting in faster and more efficient bone formation.These results bear relevance towards the manufacturing of potent off-the-shelf osteoinductive materials and outline the broader paradigm of engineering immunoinstructive implants to enhance tissue regeneration.
基金Project (2005CB623904) supported by the National Basic Research Program of ChinaProject (30770586) supported by the National Natural Science Foundation of China+1 种基金Project (31011120049) supported by the Australia-China special fund, International Science Linkages Program co-supported by the Department of Innovation, Industry, Science and Research of Australia, and the Ministry of Science and Technology and National Science Foundation of ChinaProject (2010ZDKG-96) supported by the major Subject of "13115" Programs of Shaan’xi Province, China
文摘A layer of porous film containing Ca and P was prepared by the micro-arc oxidation method on the surface of a novel near β biomedical Ti-3Zr-2Sn-3Mo-25Nb alloy, and then NH2- active group was introduced to the films by activation treatment. The phase composition, surface micro-topography and elemental characteristics of the micro-arc oxidation films were investigated with XRD, SEM, EDS and XPS, and the osteoinduction of the micro-arc oxidation films was tested using the simulated body fluid immersion, the in-vitro osteoblast cultivation test and animal experiment. The results show that the oxide layer is a kind of porous ceramic intermixture and contains Ca and P. The films in the simulated body fluid can induce apatite formation, resulting in excellent bioactivity. The cell test discovers that osteoblasts can grow well on the surface of micro-arc oxidation films. And the Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy coated with active porous calcium-phosphate films shows better osteoinduction in vivo.
基金the National Key Research and Development Program of China(Grant No.2022YFC2401801)National Science Foundation of China(Grant No.52002256)+1 种基金Major Project of Sichuan Science and Technology Department(Grant Nos.2022ZDZX0029 and 2021YFS0032)Sichuan University“Zero to one”Innovation Research Project(Grant No.2022SCUH0044).
文摘How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelitis.The present study introduced a novel one-step route to realizing the co-doping of zinc oxide(ZnO)and zinc ion(Zn^(2+))in biphasic calcium phosphate(BCP)ceramics to utilize their synergistic antibacterial.Compared with the conventional BCP ceramics(BCP-Ca),the ZnO/Zn^(2+)co-doping ones(BCP-Zn)possessed strong antibacterial ability on E.coli and S.aureus as well as stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)effectively.The synergistic antibacterial mechanism of ZnO and Zn^(2+)was also investigated.BCP-Zn showed excellent osteoinductivity and angiogenesis at three months postoperatively in the canine intramuscular implantation model.Moreover,BCP-Zn exhibited excellent anti-infective ability and bone regenerative repair compared to BCP-Ca and control groups in the infected bone defect model of rat femur.Collectively,these findings suggest that the simultaneous introduction of ZnO/Zn^(2+)could have immense potential to expand the application of osteoinductive BCP ceramics in the regenerative repair of infected bone defects.
基金the National Natural Science Foundation of China(No.30200063,30070483,301070270)the Program for New Century Excellent Talents in University from the Ministry of Education of China,and the Excellent Youth Foundation of Wuhan Science and Technology Committee(No.20005006071-10)
文摘To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 （BMP2）, biodegradable collagen scaffolds （CS） were used to load BMP-2-derived peptide solutions with different concentrations （0.4 mg peptide/CS, 0.1 mg peptide/CS and pure CS, respectively）, and the implants were implanted into muscular pockets on the back of Wistar rats. Radiographs and histological analysis were performed to evaluate the ectopic bone effects. Active ectopic bone formation was seen in both groups containing the peptide at different concentration （0.4 mg and 0.1 mg）, whereas no bone formation and only fibrous tissue was seen in the pure CS group. The new bone formation induced by the peptide P24 displayed a dose-dependent and time-dependent efficiency. The new bone formation in the 0.4 mg peptide/CS group significantly increased than that of the 0.1 mg peptide/CS group. This novel BMP-2-derived peptide had excellent osteoinductive and ectopicly osteogenic properties which were similar to those of BMP2.
文摘Additive manufacturing of porous, open-cellular metal or alloy implants, fabricated by laser or electron beam melting of a powder bed, is briefly reviewed in relation to optimizing biomechanical compatibility by assuring elastic(Young's) modulus matching of proximate bone, along with corresponding pore sizes assuring osseointegration and vasculature development and migration. In addition, associated, requisite compressive and fatigue strengths for such implants are described. Strategies for optimizing osteoblast(bone cell) development and osteoinduction as well as vascularization of tissue in 3 D scaffolds and tissue engineering constructs for bone repair are reviewed in relation to the biology of osteogenesis and neovascularization in bone, and the role of associated growth factors, bone morphogenic proteins, signaling molecules and the like. Prospects for infusing hydrogel/collagen matrices containing these cellular and protein components or surgically extracted intramedullary(bone marrow) concentrate/aspirate containing these biological and cell components into porous implants are discussed, as strategies for creating living implants, which over the long term would act as metal or alloy scaffolds.
文摘This study examined the biological response of two porous calcium phosphate ceramics, hydroxyapntite （ HA ） and hydroxyapaptite/β-tricalcium phosphate （ HA/β- TCP ） scaffolds. Three different cell types , a human osteoblastic cell line （ HOS ） , primary human osteoblasts （HOB） and human mesenehymal stem cells （MSCs）, were used to examine biocompatibility and osteoinductive capacity. The experimental results showed both materials were highly biocompatible and proliferation was significantly greater on pure HA （ P 〈 0.01 ）, with a peak in proliferation at day 7. Protein levels were significantly higher （ P 〈 0.05） than the control Thermanox（ TMX （ tm） ） for both test materials. Osteoinduction of MSCs was observed on both test materials, with cells seeded on HA/ β-TCP showing greater alkaline phosphatase activity compared to HA alone, indicating an enhancement in osteoinductive property. Both materials show good potential for use as tissue engineered scaffolds.
文摘To improve the osteogenesis ability of a-tricalcium phosphate (α-TCP) bone cement, a novel BMP/ α-TCP composite bone cement was prepared. By measuring the setting time and compressive strength, the hydration characteristic of bone cement was evaluated. Animal experiments including histological observation, radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,a-TCP bone cement and BMP/α-TCP composite bone cement. Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property. Comparison experiments show that BMP/ α-TCP composite bone cement has a stronger osteogenesis ability. The gross observation of the implant site does not exhibit any inflammation or necrosis. Histological analyses reveal that the material has good osteointegration with host bone, and new bone formation is detected within the materials, which are degrading. Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation. Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement. This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability. Key words α-tricalcium phosphate (α-TCP) - bone morphogenetic proteins (BMP) - bone cement - osteogenesis - osteoinductivity - bone tissue engineering Funded by 863 Hi-Tech Research and Development Program of China (2002AA326080) and the Fund for Outstanding Young Teacher of the Education Ministry of China(2002123)
基金Supported in part by the Specialized Research Fund for theDoctoral Program of Higher Education of China(No.20060610024)
文摘The arginine-glycine-aspartic （RGD） acid peptide was grafted to the surface of apatitewollastonite （AW） ceramic in an effort to improve its cell adhesion, proliferation and osteoinduction. RGD peptide was covalently immobilized onto the surface of AW ceramic via the synthetic cross linker AA.PTS-E and 1-ethyl-3-（3-dimethylaminopropyl）carbodiimide （EDC）. The modified surfaces were characterized by attenuated total reflectance Fourier transform infrared spectroscopy （ATR-FTIR） and X-ray photoelectron spectroscopy （XPS）. The chemical analysis indicated that RGD peptide had been immobilized onto the AW surface successfully. The growth of osteoblast-like cells （MG63） showed that modifying the AW surface with RGD peptide enhanced the cell adhesion and proliferation. And the histological evaluation of RGD-AW showed that the bone regeneration and remodeling process were significantly enhanced compared to the original AW ceramics after 2, 4 and 8 weeks implantation in rabbit＇s femoral condyles.
基金This study was financially supported by 863 Hj-Tech ResearchDevelopment Program of China(2002AA326080)The Fund for Youth Teacher of Education Mlinistry of China(2002123).
文摘To develop a novel degradable poly (L-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) bioactive materials for bone tissueengineering, β-TCP powder was produced by a new wet process. Porous scaffolds were prepared by three steps, i.e. solventcasting, compression molding and leaching stage. Factors influencing the compressive strength and the degradation behaviorof the porous scaffold, e.g. weight fraction of pore forming agent-sodium chloride (NaCl), weight ratio of PLLA: β-TCP,the particle size of β-TCP and the porosity, were discussed in details. Rat marrow stromal cells (RMSC) were incorporatedinto the composite by tissue engineering approach. Biological and osteogenesis potential of the composite scaffold weredetermined with MTT assay, alkaline phosphatase (ALP) activity and bone osteocalcin (OCN) content evaluation. Resultsshow that PLLA/β-TCP bioactive porous scaffold has good mechanical and pore structure with adjustable compressive strengthneeded for surgery. RMSCs seeding on porous PLLA/β-TCP composite behaves good seeding efficacy, biocompatibility andosteoinductive potential. Osteoprogenitor cells could well penetrate into the material matrix and begin cell proliferation andosteogenic differentiation. Osseous matrix could be formed on the surface of the composite after culturing in vitro. It isexpected that the PLLA/β-TCP porous composites are promising scaffolds for bone tissue engineering in prosthesis surgery.
基金The European Union(European Social Fund-ESF)Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework(NSRF)-Research Funding Program:Heracleitus Ⅱ
文摘AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7(rhB MP-7) for the treatment of nonunions.METHODS Bone morphogenetic proteins(BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients(80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent jointswere also carried out. Factors related to the patient(age, gender), the nonunion(location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure(graft and fixation type, amount of rhB MP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ~2 test was performed.RESULTS Eighty point nine percent of the nonunions treated with rh BMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients(17.8%) and it was apparent in the routine radiologi-cal evaluation of the nonunion site, in a mean time of 5.5 mo after the rh BMP-7 application(range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhB MP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient's gender was the only important factor for the development of heterotopic ossification(P = 0.007). CONCLUSION Heterotopic ossification after the use of rh BMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.
基金Project (No. 2005CB623901) supported by the National Basic Research Program (973) of China
文摘The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented,but little research has been performed on rodent animals,e.g.,mice.In this study,we report osteoinduction in a mouse model.Thirty mice were divided into two groups.BCP materials (Sample A) and control ceramics (Sample B) were implanted into the leg muscle,respectively.Five mice in each group were killed at 15,30,and 45 d after surgery.Sample A and Sample B were harvested and used for hematoxylin and eosin (HE) staining,immunohistochemistry (IHC) staining,and Alizarin Red S staining to check bone formation in the biomaterials.Histological analysis showed that no bone tissue was formed 15 d after implantation (0/5) in either of the two groups.Newly-formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after implantation;the average amounts of newly-formed bone tissues were approximately 5.2% and 8.6%,respectively.However,we did not see any bone tissue in Sample B until 45 d after implantation.Bone-related molecular makers such as bone morphogenesis protein-2 (BMP-2),collagen type I,and osteopontin were detected by IHC staining in Sample A 30 d after implantation.In addition,the newly-formed bone was also confirmed by Alizarin Red S staining.Because this is the report of osteoinduction in the rodent animal on which all the biotechnologies were available,our results may contribute to further mechanism research.
基金supported by the National Key Research and Development Program of China(No.2017YFC1104102)National Natural Science Foundation of China(Nos.31370958,21875044)+1 种基金Key Program of Natural Science Foundation of Fujian Province(No.2018Y0056)the International Scientific Partnership Program ISPP at King Saud University for funding this research work through ISPP-17-94(2)。
文摘Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self-healing nano hybrid hydrogel was on-demand prepared via a fast(within 30 s)and easy gelation approach by reversible Schiff base formed between-CH=O of oxidized sodium alginate(OSA)and-NH2 of glycol chitosan(GCS)mixed with calcium phosphate nanoparticles(CaP NPs).Its raw materials can be ready in large quantities by a simple synthesis process.The mechanical strength,degradation and swelling behavior of the hydrogel can be readily controlled by simply controlling the molar ratio of-CH=O and-NH2.This hydrogel exhibits pH responsiveness,good degradability and biocompatibility.The hydrogel used as the matrix for mesenchymal stem cells can significantly induce the proliferation,differentiation and osteoinduction in vitro.These results showed this novel hydrogel is an ideal candidate for applications in bone tissue regeneration and drug delivery.
基金supported by the National Key R&D Program of China(2018YFC1105300)the National Natural Science Foundation of China(81771050,81700931,81901017)+1 种基金the Special Fund for Technical Innovation of Hubei Province(2017AHB046)the Natural Science Foundation of Hubei Province(2017CFA025).
文摘The immune response of a biomaterial determines its osteoinductive effect.Although the mechanisms by which some immune cells promote regeneration have been revealed,the biomaterial-induced immune response is a dynamic process involving multiple cells.Currently,it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials.Herein,we investigated the roles of macrophages and dendritic cells(DCs)during the osteoinduction of biphasic calcium phosphate(BCP)scaffolds.We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation,resulting in low T cell response and efficient osteogenesis.Accordingly,a dual-targeting nano-in-micro scaffold(BCP loaded with gold nanocage,BCP-GNC)was designed to regulate the immune responses of macrophages and DCs.Through a dual-wavelength photosensitive switch,BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs,creating a desirable inflammatory environment for osteogenesis.This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.
基金Funded by the National Basic Research Program of China (973 Program)(No. 2005CB623900-G)
文摘HA/TCP and HA rods （φ5 mm×10 mm） were made for implantation in New Zealand white rabbit with different condition. Sixty three rabbit were divided into three groups： group 1 （n=18）, group 2 （n=27） and group 3 （n=18）. In group 1, 10 mm radius was defected, and one HA/TCP rod was implanted in the muscle a distant away from the bone defect area. In group 2, also, 10 mm radius was defected, one HA rod was implanted in the muscle a distant away from the bone defect area. In group 3, two HA/TCP rods were implanted in the dorsal muscle of the rabbit with bone intact. Histological observation showed that in group 1, some new bone was found only two months after implantation （n=2）, and obvious immature woven bone could be observed in these bioceramics from the 3rd month on. However, in group 3, bone began to be found 6 months after implantation （n=2）. In group 2, we could not find any bone tissue up to 9 month’s observation. These results suggest that, first, the bone defect model could significantly accelerate bone formation at non-osseous sites in rabbits; second,. HA/TCP bioceramics were confirmed with osteoinductive property while HA bioceramics without osteoinductive property nearly. Thus, bone defect might be a good animal model for further researches for osteoinductive bioceramics.
文摘This paper reports the results of 24 cases of bone defect resulting from bone tumor or tumor condition excision, and of posterior spinal fusion, treated by human bone matrix gelatin. The success rate of bone defect repair and spinal fusion is 91. 67 %. The results suggest that human bone matrix gelatin has. excellent osteoinductive effect and is ideal substitute for bone autografts.
文摘Porous β-tricalcium phosphate (TCP) displays osteoinductivity in certain animals in the absence of osteoinductive agents. We evaluated whether the microstructure may be an important determinant of osteoinduction, and also investigated how bone formation was promoted using β-TCP combined with bone marrow aspirates. We prepared two types of β-TCP, namely, β-TCP A, which possessed interconnected macropores and micropores, and β-TCP B, which possessed macropores but had less detectable micropores. These were implanted with or without marrow in canine muscles. Bone formation and the resorption of each β-TCP implant were evaluated histologically. Newly formed bone began to appear at day 42 in the implants of β-TCP A alone, but the implants of β-TCP B alone did not show any bone formation by day 42. Meanwhile, bone formation was already evident on day 14 by loading with bone marrow aspirates with or without micropores. By immunohistochemistry, the number of cathepsin K-positive cells (osteoclasts) increased as time passed in the implants of β-TCP A alone, while the number of the osteoclasts did not change obviously in the implants of β-TCP B alone from day 14 to 56. Reticular fibrils were evident within the β-TCP A, and were barely observed in the β-TCP B in the silver impregnation. The present result would bring about the possible role to enhance the importance of the surface microstructure for the better osteoinductivity. Our findings suggest that the combination of porous β-TCP and bone marrow facilitates bone formation.
