The Role of Microstructure of Highly Purified Beta-Tricalcium Phosphate for Osteoinduction in Canine Dorsal Muscles

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.

Osteoinduction and Osteoconduction with Porous Beta-Tricalcium Phosphate Implanted after Fibular Resection in Humans

Osteoinductive properties of β-TCP remain unknown in humans. It is important to improve the bone grafts which have been the standard treatment for bone defect due to their biocompatibility and bone-healing properties. The purpose of this study was to radiologically clarify the bone forming property of β-TCP by evaluating the replacement of β-TCP by newly formed bone in the defect after fibular resection and to examine the histological features of a β-TCP specimen three months after grafting. Radiographs of 17 patients who underwent β-TCP grafting were evaluated. Osteoinductive and osteoconductive properties were assessed by examining bone formation from the remnant fibula, periosteum, and β-TCP alone. In one case, β-TCP was removed later because of postoperative complications and was evaluated histologically. Twenty two of 34 sites between the remnant fibula and β-TCP had achieved good bone regeneration. Five of 14 sites between the periosteum and β-TCP had achieved good bone regeneration. We found immature but evident bone formation in three cases with no osseous and periosteal sites. Histological analysis revealed bone formation on the outer macropore surface of β-TCP. Some blood vessels formed in the macropores expressed CD31 and CD34, while a few lymphatic vessels expressed CD34 and podoplanin. Thus, the osteoinductive ability of β-TCP alone was demonstrated in humans radiographically for the first time. The histological morphology of β-TCP was demonstrated at an early stage after grafting in humans.

Strategies for creating living, additively manufactured, open-cellular metal and alloy implants by promoting osseointegration,osteoinduction and vascularization: An overview

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.

Osteoinduction by Ca-P biomaterials implanted into the muscles of mice

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.

Design and evaluation of a novel sub-scaffold dental implant system based on the osteoinduction of micro-nano bioactive glass

Alveolar ridge atrophy brings great challenges for endosteal implantation due to the lack of adequate vertical bone mass to hold the implants.To overcome this limitation,we developed a novel dental implant design:sub-scaffold dental implant system(SDIS),which is composed of a metal implant and a micro-nano bioactive glass scaffold.This implant system can be directly implanted under mucous membranes without adding any biomolecules or destroying the alveolar ridge.To evaluate the performance of the novel implant system in vivo,SDISs were implanted into the subepicranial aponeurosis space of Sprague–Dawley rats.After 6 weeks,the SDIS and surrounding tissues were collected and analysed by micro-CT,scanning electron microscopy and histology.Our results showed that SDISs implanted into the sub-epicranial aponeurosis had integrated with the skull without any mobility and could stably support a denture.Moreover,this design achieved alveolar ridge augmentation,as active osteogenesis could be observed outside the cortical bone.Considering that the microenvironment of the sub-epicranial aponeurosis space is similar to that of the alveolar ridge,SDISs have great potential for clinical applications in the treatment of atrophic alveolar ridges.The study was approved by the Animal Care Committee of Guangdong Pharmaceutical University(approval No.2017370).

A fast on-demand preparation of injectable self-healing nanocomposite hydrogels for efficient osteoinduction

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.

Preparation of multigradient hydroxyapatite scaffolds and evaluation of their osteoinduction properties

Porous hydroxyapatite(HA)scaffolds are often used as bone repair materials,owing to their good biocompatibility,osteoconductivity and low cost.Vascularization and osteoinductivity of porous HA scaffolds were limited in clinical application,and these disadvantages were need to be improved urgently.We used water-in-oil gelation and pore former methods to prepare HA spheres and a porous cylindrical HA container,respectively.The prepared HA spheres were filled in container to assemble into composite scaffold.By adjusting the solid content of the slurry(solid mixture of chitin sol and HA powder)and the sintering temperature,the porosity and crystallinity of the HA spheres could be significantly improved;and mineralization of the HA spheres significantly improved the biological activity of the composite scaffold.The multigradient(porosity,crystallinity and mineralization)scaffold(HA-700)filled with the mineralized HA spheres exhibited a lower compressive strength;however,in vivo results showed that their vascularization ability were higher than those of other groups,and their osteogenic Gini index(Go:an index of bone mass,and inversely proportional to bone mass)showed a continuous decrease with the implantation time.This study provides a new method to improve porous HA scaffolds and meet the demands of bone tissue engineering applications.

Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

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.

The Clinical Application of Human Bone Matrix Gelatin

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Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis

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.

Local Application of Alendronate on <i>β</i>-Tricalcium Phosphate Accelerated Induction of Osteogenesis with Formation of Giant Osteoclast-Like Cell

Intrinsic osteoinductivity—the ability to induce bone formation in ectopic sites without addition of osteogenic factors has been reported in various porous materials. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells are thought to play an important role in material-induced osteoinduction. To investigate the influence of osteoclastic activity on intrinsic osteoinduction, we loaded alendronate (10–2 , 10–4 , and 10–6 M) onto porous β-tricalcium phosphate (β-TCP) blocks to inhibit osteoclastic activity, and evaluated osteoinductivity by implantation of the blocks into the dorsal muscles of adult beagle dogs. Alendronate-loaded porous β-TCP blocks increased both speed and amount of osteoinduction, as measured 4 weeks after implantation, with the 10–4 M alendronate-loaded β-TCP being especially active. This finding indicates that β-TCP loaded with 10–4 M alendronate might prove crucial in providing the desirable balance between the degradation rate of bone scaffolds and their osteoinductive replacement. Thus, material-induced osteoinduction may be controlled by local application of alendronate, establishing alendronate loading as a promising therapeutic approach.

Osteogenesis Capacity of a Novel BMP/α-TCP Bioactive Composite Bone Cement

To improve the osteogenesis ability of α-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,α-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.

Triple-functional bone adhesive with enhanced internal fixation,bacteriostasis and osteoinductive properties for open fracture repair

At present,effective fixation and anti-infection implant materials represent the mainstay for the treatment of open fractures.However,external fixation can cause nail tract infections and is ineffective for fixing small fracture fragments.Moreover,closed reduction and internal fixation during the early stage of injury can lead to potential bone infection,conducive to bone nonunion and delayed healing.Herein,we designed a bone adhesive with anti-infection,osteogenic and bone adhesion fixation properties to promote reduction and fixation of open fractures and subsequent soft tissue repair.It was prepared by the reaction of gelatin(Gel)and oxidized starch(OS)with vancomycin(VAN)-loaded mesoporous bioactive glass nanoparticles(MBGNs)covalently cross-linked with Schiff bases.Characterization and adhesion experiments were conducted to validate the successful preparation of the Gel-OS/VAN@MBGNs(GOVM-gel)adhesive.Meanwhile,in vitro cell experiments demonstrated its good antibacterial effects with the ability to stimulate bone marrow mesenchymal stem cell(BMSCs)proliferation,upregulate the expression of alkaline phosphatase(ALP)and osteogenic proteins(RunX2 and OPN)and enhance the deposition of calcium nodules.Additionally,we established a rat skull fracture model and a subcutaneous infection model.The histological analysis showed that bone adhesive enhanced osteogenesis,and in vivo experiments demonstrated that the number of inflammatory cells and bacteria was significantly reduced.Overall,the adhesive could promote early reduction of fractures and antibacterial and osteogenic effects,providing the foothold for treatment of this patient population.

Engineering of immunoinstructive extracellular matrices for enhanced osteoinductivity

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.

Continuously released Zn^(2+)in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties

Long-term nonunion of bone defects has always been a major problem in orthopedic treatment.Artificial bone graft materials such as Poly(lactic-co-glycolic acid)/β-tricalcium phosphate(PLGA/β-TCP)scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity.However,insufficient mechanical properties,lack of osteoinductivity and infections after implanted limit its large-scale clinical application.Hence,we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/β-TCP using low temperature rapid prototyping 3D printing technology.We first screened the scaffolds with 1 wt%Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity.As designed,the scaffold had a multi-level porous structure of biomimetic cancellous bone,and the Young’s modulus(63.41±1.89 MPa)and compressive strength(2.887±0.025 MPa)of the scaffold were close to those of cancellous bone.In addition,after a series of in vitro and in vivo experiments,the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation,as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/β-TCP scaffold without zinc particles.We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/β-catenin,P38 MAPK and NFkB pathways.This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials.We envision that this scaffold may become a new strategy for clinical treatment of bone defects.

The material and biological characteristics of osteoinductive calcium phosphate ceramics

The discovery of osteoinductivity of calcium phosphate(Ca-P)ceramics has set an enduring paradigm of conferring biological regenerative activity to materials with carefully designed structural characteristics.The unique phase composition and porous structural features of osteoinductive Ca-P ceramics allow it to interact with signaling molecules and extracellular matrices in the host system,creating a local environment conducive to new bone formation.Mounting evidence now indicate that the osteoinductive activity of Ca-P ceramics is linked to their physicochemical and three-dimensional structural properties.Inspired by this conceptual breakthrough,many laboratories have shown that other materials can be also enticed to join the rank of tissue-inducing biomaterials,and besides the bones,other tissues such as cartilage,nerves and blood vessels were also regenerated with the assistance of biomaterials.Here,we give a brief historical recount about the discovery of the osteoinductivity of Ca-P ceramics,summarize the underlying material factors and biological characteristics,and discuss the mechanism of osteoinduction concerning protein adsorption,and the interaction with different types of cells,and the involvement of the vascular and immune systems.

Promoting proliferation and differentiation of BMSCs by green tea polyphenols functionalized porous calcium phosphate

In this article,we proposed a facile protocol to functionalize porous calcium phosphate ceramics(PCPC)using dietary tea polyphenols(TP).TP molecules was attracted and anchored by Ca2t ions from the surface of CPC.These TP molecules modulated the nucleation and crystallization of calcium phosphate nanorods assemblies on the surface of PCPC.Our results prove that these calcium phosphate nanorods assemblies accompanies functional groups of TP make PCPC/TP effectively promote proliferation and differentiation of bone mesenchymal stem cells(BMSCs).We inferred that these calcium phosphate nanorods assemblies might change the surface microenvironment of PCPC,which is critical to promote the proliferation and differentiation of BMSCs.Compared with naked PCPC,PCPC/TP obviously increased BMP2,ErK/MAPK and JNK/MAPK level and mineralization capacity of cells(ALP level).

Optimal regenerative repair of large segmental bone defect in a goat model with osteoinductive calcium phosphate bioceramic implants

So far,how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic.In this study,a strategy of combining osteoinductive biphasic calcium phosphate(BCP)bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects(3.0 cm in length)in goat femur model.The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa,and total porosity of 84%.The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells(BMSCs).The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage,promoting the osteogenic process both guided and induced by the BCP scaffolds.At 9 months postoperatively,good integration between the implants and host bone was observed,and a large amount of newborn bones formed,accompanying with the degradation of the material.At 18 months postoperatively,almost the complete new bone substitution in the defect area was achieved.The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery.Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects.The current study could provide an effective method to treat the clinical large segmental bone defects.

Fabrication and biological evaluation of 3D-printed calcium phosphate ceramic scaffolds with distinct macroporous geometries through digital light processing technology

Digital light processing(DLP)-based 3D printing technique holds promise in fabricating scaffolds with high precision.Here raw calcium phosphate(CaP)powders were modified by 5.5%monoalcohol ethoxylate phosphate(MAEP)to ensure high solid loading and low viscosity.The rheological tests found that photocurable slurries composed of 50wt%modified CaP powders and 2wt%toners were suitable for DLP printing.Based on geometric models designed by computer-aided design(CAD)system,three printed CaP ceramics with distinct macroporous structures were prepared,including simple cube,octet-truss and inverse face-centered cube(fcc),which presented the similar phase composition and microstructure,but the different macropore geometries.Inverse fcc group showed the highest porosity and compressive strength.The in vitro and in vivo biological evaluations were performed to compare the bioactivity of three printed CaP ceramics,and the traditional foamed ceramic was used as control.It suggested that all CaP ceramics exhibited good biocompatibility,as evidence by an even bone-like apatite layer formation on the surface,and the good cell proliferation and spreading.A mouse intramuscular implantation model found that all of CaP ceramics could induce ectopic bone formation,and foam group had the strongest osteoinduction,followed by inverse fcc,while cube and octet-truss had the weakest one.It indicated that macropore geometry was of great importance to affect the osteoinductivity of scaffolds,and spherical,concave macropores facilitated osteogenesis.These findings provide a strategy to design and fabricate high-performance orthopedic grafts with proper pore geometry and desired biological performance via DLP-based 3D printing technique.

Whisker of biphasic calcium phosphate ceramics: Osteoimmunomodulatory behaviors

Immune systems play a critical role in the regulation of bone formation and homeostasis,which arouses a growing interest in the development of biomaterials that can modulate both immune response and osteogenesis.In this study,biphasic calcium phosphate(BCP)ceramics were modified with different whiskered surface,and their effects on macrophage polarization and functional status were investigated.The results showed that compared to BCP-W ceramics with long and solid whiskers,BCPHW ceramics with short and hollow whiskers surface were conducive to protein adsorption and macrophage elongation.Furthermore,BCP-HW ceramics down-regulated the expression of M1 macrophage markers(Il1β,Tnfα,and iNos),promoted the expression of M2 macrophage markers(Il10 and Arg)and growth factors(Tgfβ1 and Bmp2),which might be attributed to the differential integrin expression regulated by different whisker structures.The conditioned medium derived from the supernatant of macrophage/whiskered ceramic co-culture was further used to culture MC3T3-E1 pre-osteoblasts to evaluate the effects of whiskered ceramic-mediated macrophage secretion on osteogenesis in vitro.Compared with BCP-W ones,the secretion pattern induced by BCP-HW ceramics could promote the expression of bone markers in pre-osteoblasts,which might due to the activation of intracellular signaling cascades like BMP/Smad and TGF-β/Smad signaling pathways.A murine intramuscular implantation model suggested that after implantation for 1,2,and 3 weeks,BCP-HW ceramics drove the switch of macrophages to ARG+wound-healing M2 phenotype,while BCP-W ceramics increased the proportion of iNOS+M1 inflammatory macrophages.At 2 months,only BCP-HW could induce ectopic bone formation.Taken together,these results indicated that BCP ceramics with hollow whiskers were capable of creating a proper inflammatory microenvironment to induce bone formation.These whiskered BCP ceramics with good osteo-immunomodulatory capacity hold promise in serving as bone grafts to achieve desired bone repair and regeneration.