Canine ACL reconstruction with an injectable hydroxyapatite/collagen paste for accelerated healing of tendon-bone interface

Healing of an anterior cruciate ligament(ACL)autologous graft in a bone tunnel occurs through the formation of fibrovascular scar tissue,which is structurally and compositionally inferior to normal fibrocartilaginous insertion and thus may increase the reconstruction failure and the rate of failure recurrence.In this study,an injectable hydroxyapatite/type I collagen(HAp/Col I)paste was developed to construct a suitable local microenvironment to accelerate the healing of bone-tendon interface.Physicochemical characterization demonstrated that the HAp/Col I paste was injectable,uniform and stable.The in vitro cell culture illustrated that the paste could promote MC3T3-E1 cells proliferation and osteogenic expression.The results of a canine ACL reconstruction study showed that the reconstructive ACL had similar texture and color as the native ACL.The average width of the tunnel,total bone volume,bone volume/tissue volume and trabecular number acquired from micro-CT analysis suggested that the healing of tendon-bone interface in experimental group was better than that in control group.The biomechanical test showed the maximal loads in experimental group achieved approximately half of native ACL’s maximal load at 24 weeks.According to histological examination,Sharpey fibers could be observed as early as 12 weeks postoperatively while a typical four-layer transitional structure of insertion site was regenerated at 48 weeks in the experimental group.The injectable HAp/Col I paste provided a biomimetic scaffold and microenvironment for early cell attachment and proliferation,further osteogenic expression and extracellular matrix deposition,and in vivo structural and functional regeneration of the tendon-bone interface.

Bio-inspired Hydroxyapatite/Gelatin Transparent Nanocomposites

Hydroxyapatite(HA)nanoparticles impart outstanding mechanical properties to organicinorganic nanocomposites in bone.Inspired by the composite structure of HA nanoparticles and collagen in bone,a high performance HA/gelatin nanocomposite was first developed.The nanocomposites have much better mechanical properties(elongation at break 29.9%,tensile strength 90.7 MPa,Young’s modulus 5.24 GPa)than pure gelatin films(elongation at break 9.3%,tensile strength 90.8 MPa,Young’s modulus 2.5 GPa).In addition,the composite films keep a high transmittance in visible wavelength range from 0%to 60%of the HA solid content.These differences in properties are attributed to the homogeneous distribution of HA nanoparticles in the gelatin polymer matrix and the strong interaction between the particle surfaces and the gelatin molecules.This protocol should be promising for HA-based nanocomposites with enhanced mechanical properties for biomedical applications.

Effect of Fluoride on the Ion-association of Calcium Phosphate and Crystallization of Hydroxyapatite

Using a titration setup to accurately control the reaction conditions and in situ monitor the reaction,we showed that fluoride exhibited negligible effects on the ion association process of calcium and phosphate and the formation of ACP nanospheres in a buffer solution with constant ionic strength.However,the stability of ACP increased with increasing fluoride concentration,which was ascribed to the inhibitory effect of fluoride on the aggregation of ACP nanospheres and the nucleation of nanocrystals on the surface of ACP nanospheres.Furthermore,fluoride could inhibit the lateral growth of HAP nanosheets and promote the formation of rod-like crystals.These results further improve our understanding of the crystallization pathway of HAP crystals and the regulatory effects of fluoride.

Ionic liquid-assisted preparation of hydroxyapatite and its catalytic performance for decarboxylation of itaconic acid

The synthesis of methacrylic acid from biomass-derived itaconic acid is a green route,for it can get rid of the dependence on fossil resource.In order to solve the problems on this route such as use of a preciousmetal catalyst and a corrosive homogeneous alkali,we prepared a series of hydroxyapatite catalysts by an ionic liquid-assisted hydrothermal method and evaluated their catalytic performance.The results showed that the ionic liquid[Bmim]BF_(4) can affect the crystal growth of hydroxyapatite,provide fluoride ion for fluorination of hydroxyapatite,and adjust the surface acidity and basicity,morphology,textural properties,crystallinity,and composition of hydroxyapatite.The[Bmim]BF4 dosage and hydrothermal temperature can affect the fluoride ion concentration in the hydrothermal system,thus changing the degree of fluoridation of hydroxyapatite.High fluoride-ion concentration can lead to the formation of CaF_(2) and thus significantly decrease the catalytic performance of hydroxyapatite.The hydrothermal time mainly affects the growth of hydroxyapatite crystals on the c axis,leading to different catalytic performance.The suitable conditions for the preparation of this fluoridized hydroxyapatite are as follows:a mass ratio of[Bmim]BF4 to calcium salt=0.2:1,a hydrothermal time of 12 h,and a hydrothermal temperature of 130℃.A maximal methacrylic acid yield of 54.7%was obtained using the fluoridized hydroxyapatite under relatively mild reaction conditions(250℃ and 2 MPa of N_(2))in the absence of a precious-metal catalyst and a corrosive homogeneous alkali.

Characterization of Hydroxyapatite Extracted from Crab Shell Using the Hydrothermal Method with Varying Holding Times

Hydroxyapatite(HA)is a bio ceramic commonly utilized in bone tissue engineering due to its bioactive and osteoconductive properties.Crab shells are usually disregarded as waste material despite their significant CaCO_(3) content,and have not been widely utilized in the synthesis of HA.This study aims to synthesize and analyze HA derived from crab shells using the hydrothermal method with different durations of holding time.This study utilized precipitated calcium carbonate(PCC)derived from crab shells.With a hydrothermal reactor set at 160℃ and varying holding times of 14(HA_14),16(HA_16),and 18(HA_18)h,a PCC and(NH4)2HPO4 mixture was used to synthesize HA.The synthesis results were analyzed using scanning electron microscopy(SEM),fourier transform infrared spectroscopy(FTIR),and X-ray diffraction(XRD)tests.This study has accomplished the synthesis of HA from crab shells.Nonetheless,the final product of synthesis still contained CaCO_(3) as an impurity.The prolonged hydrothermal holding time of 14 to 18 h resulted in a reduction of impurities while increasing the percentage of crystal weight and crystallite size of HA.Specimen CH_18 is the best-quality product generated in this study.This specimen produced HA with the highest percentage of crystal weight and crystallite size compared to the other specimens.Furthermore,specimen CH_18 exhibited the lowest concentration of impurities.The Ca/P ratio in this specimen was also the closest to 1.67.The Ca/P ratio,crystallite size,and crystal weight percentage of this specimen are 1.54,19.06 nm,and 99.1%,respectively.

Effect of nano-hydroxyapatite/collagen composite and bone morphogenetic protein-2 on lumbar intertransverse fusion in rabbits

Objective: To investigate the effect of nano hydroxyapatite/collagen (nHA/collagen) composite as a graft extender and enhancer when combined with recombinant human bone morphogenetic protein 2 (rhBMP 2) on lumbar intertransverse fusion in rabbits. Methods: Sixty four adult female New Zealand white rabbits, aged 1 year and weighing 3.5 4.5 kg, underwent similar posterolateral intertransverse process arthrodesis and were randomly divided into 4 groups based on different grafts: autogenous cancellous bone alone (ACB group), nHA/collagen alone (HAC group), half autogenous cancellous bone and half nHA/collagen (ACB+HAC group) and nHA/collagen combined with rhBMP 2 (HAC+BMP group). The fusion masses were analyzed by manual palpation, radiography, biomechanical testing and histological examination. Results: Fusion was observed in 4 cases in the 6th week and in 5 cases in the 10th week after surgery in ACB group. No case showed fusion in HAC group. In ACB+HAC group, there was fusion in 3 cases in the 6th week and in 4 cases in the 10th week after surgery. In HAC+BMP group, fusion in 1 case was found in the 4th week, in 5 cases in the 6th week and in 6 cases in the 10th week after surgery. It suggested that ACB, ACB+HAC and HAC+BMP groups showed similar fusion ratio and mechanical strength in the 6th and 10th week after surgery. According to the microstructure analysis of the samples, nHA/collagen had no negative effect when implanted together with ilium autograft. In HAC+BMP group, new bone like tissue was observed in the 2nd week postoperatively, and nearly all of the implanted composites were replaced by mature bone matrix and new bones in 10th week postoperatively. Conclusions: The nHA/collagen, especially combined with rhBMP 2, is a promising bone substitute, for it has quick biodegradation, fine bone bending ability, and high osteoconductivity on posterolateral spinal fusion in rabbits.

Influence of Ca/P ratio on the catalytic performance of hydroxyapatite for decarboxylation of itaconic acid to methacrylic acid

Methacrylic acid,an important organic chemical,is commercially manufactured starting from fossil feedstock.The decarboxylation of itaconic acid derived for biomass is a green route to the synthesis of methacrylic acid.In view of the problems existing in the researches on this route such as use of noble metal catalyst,harsh reaction conditions and low desired-product yield,we prepared a series of hydroxyapatite catalysts with different Ca/P molar ratios and evaluated their catalytic performance.The results showed that the hydroxyapatite catalyst with a Ca/P molar ratio of 1.58 had the best catalytic activity.The highest yield of MAA up to 61.2%was achieved with basically complete conversion of itaconic acid under the suitable reaction conditions of 1 equivalent of NaOH,2 MPa of N_(2),250℃,and 2 h.On this basis,a reaction network for the decarboxylation of itaconic acid to methacrylic acid catalyzed by hydroxyapatite was established.With the aid of catalyst characterization using X-ray powder diffraction,NH3/CO2 temperature-programmed desorption,N_(2)physisorption,inductively coupled plasma optical emission spectrometry,and scanning electron microscopy,we found that the distribution of surface acid sites and basic sites,crystal growth orientation,texture properties and morphology of hydroxyapatite varied with the Ca/P molar ratio.Furthermore,the change of the crystal growth orientation and its influence on the surface acidity and alkalinity were clarified.

Comparative study of chitosan/fibroin–hydroxyapatite and collagen membranes for guided bone regeneration in rat calvarial defects: micro-computed tomography analysis

This study aimed to utilize micro-computed tomography （micro-CT） analysis to compare new bone formation in rat calvarial defects using chitosan/fibroin-hydroxyapatite （CFB-HAP） or collagen （Bio-Gide） membranes. Fifty-four （54） rats were studied. A circular bony defect （8 mm diameter） was formed in the centre of the calvaria using a trephine bur. The CFB-HAP membrane was prepared by thermally induced phase separation. In the experimental group （n= 18）, the CFB-HAP membrane was used to cover the bony defect, and in the control group （n= 18）, a resorbable collagen membrane （Bio-Gide） was used. In the negative control group （n= 18）, no membrane was used. In each group, six animals were euthanized at 2, 4 and 8 weeks after surgery. The specimens were then analysed using micro-CT. There were significant differences in bone volume （BV） and bone mineral density （BMD） （P〈O.05） between the negative control group and the membrane groups. However, there were no significant differences between the CFB-HAP group and the collagen group. We concluded that the CFB-HAP membrane has significant potential as a guided bone regeneration （GBR） membrane.

The crystal growth of hydroxyapatite in presence of collagens

The crystal growth of hydroxyapatite (HAP) seeds in presence of the abnormal collagen secreted by the chondrocyte grown in media containing free radical sources or fulvic acid and the type II collagen (pig cartilage) damaged by · OH and fulvic acid(FA) from potable water in endemic region of Kaschin-Beck disease (KBD) was studied. The results showed that in the former case, the abnormal collagen rich in type I collagen promoted mineralization in contrast with the type n collagen. The oxidatively damaged type II collagen became less inhibitive or even promotive. In all cases, the reaction followed a second order kinetics. The powder X-diffraction analysis and SEM observation indicated that the damaged type II collagen lowers the crystalinity in the beginning and made the final crystal more agglomerated. All the results showed that the abnormal and the damaged cartilage matrix affected the bimineralization and was likely to have played an important role in the development of KBD.

Repair of radius defect with bone-morphogenetic-protein loaded hydroxyapatite/collagen-poly(L-lactic acid) composite

Objective: To explore the method to repair bone defect with bone-morphogenetic-protein loaded hydroxyapatite/collagen-poly(L-lactic acid) composite. Methods: 18 adult beagle dogs were randomly divided into 3 groups. In Group A, bone-morphogenetic-protein (BMP) loaded hydroxyapatite/collagen-poly(L-lactic acid) (HAC-PLA) scaffold was implanted in a 2 cm diaphyseal defect in the radius. In Group B, unloaded pure HAC-PLA scaffold was implanted in the defects. No material was implanted in Group C (control group). The dogs were sacrificed 6 months postoperatively. Features of biocompatibility, biodegradability and osteoinduction were evaluated with histological, radiological examinations and bone mineral density (BMD) measurements. Results: In Group A, the radius defect healed after the treatment with BMP loaded HAC-PLA. BMD at the site of the defect was higher than that of the contralateral radius. Fibrous union developed in the animals of the control group. Conclusions: BMP not only promotes osteogenesis but also accelerates degradation of the biomaterials. Optimized design parameters of a three-dimensional porous biomaterial would give full scope to the role of BMP as an osteoinductive growth factor.

Investigation of the Nd-Ce-Mg-Zn/Substituted Hydroxyapatite Effect on Biological Properties and Osteosarcoma Cells

Cancerous diseases and diseases resulting from bacteria and fungi are some of the pressures that humans face.Therefore,the development of biomaterials that are resistant to cancerous diseases,bacteria,and fungi has become one of the requirements of the medical field to extend the life of the biomaterial and fight pathogens after implanting these materials inside the human body.One of the important biomaterials used in the field of orthopedics is hydroxyapatite.In this research,Nano substituted hydroxyapatite was prepared by the wet precipitation method,including replacing 5%of the calcium ions with neodymium,cerium,magnesium,and zinc ions in cationic substitution.Many tests were carried out to characterize the prepared material.The biological properties were evaluated by examining the resistance of the substituted hydroxyapatite to bacteria and fungi,in addition to testing the effect of the material on normal cells and bone cancer cells.The results showed a new structure of hydroxyapatite after the substitution process and a significant improvement in the biological properties of the prepared biomaterial compared to other researches.

Azoximer bromide and hydroxyapatite:promising immune adjuvants in cancer

Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations.There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers.Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response,followed by the adaptive immune response.The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells.Most immune adjuvants are associated with a vaccine or incorporated into the new generation of m RNA vaccines.Few immune adjuvants are used as drugs.Hydroxyapatite(HA)ceramics and azoximer bromide(AZB)are overlooked molecules that were used in early clinical trials,which demonstrated clinical efficacy and excellent tolerance profiles.HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas.AZB,an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia,the Commonwealth of Independent States,and Slovakia for infectious and inflammatory diseases,is and now being developed for use in cancer with promising results.These two immune adjuvants can be combined in various immunotherapy strategies.

Comparative evaluation of the physicochemical properties of nano-hydroxyapatite/collagen and natural bone ceramic/collagen scaffolds and their osteogenesis-promoting effect on MC3T3-E1 cells

The use of various types of calcium phosphate has been reported in the preparation of repairing materials for bone defects.However,the physicochemical and biological properties among them might be vastly different.In this study,we prepared two types of calcium phosphates,nano-hydroxyapatite(nHA)and natural bone ceramic(NBC),into 3D scaffolds by mixing with type I collagen(CoL),resulting in the nHA/CoL and NBC/CoL scaffolds.We then evaluated and compared the physicochemical and biological properties of these two calcium phosphates and their composite scaffold with CoL.Scanning electron microscopy(SEM),X-ray photoelectron spectroscopy(XPS),Fourier-transform infrared spectroscopy(FTIR),X-ray diffraction spectroscopy(XRD)and compressive tests were used to,respectively,characterize the morphology,composition,distribution and the effect of nHA and NBC to collagen.Next,we examined the biological properties of the scaffolds using cytotoxicity testing,flow cytometry,immunofluorescence staining,biocompatibility testing,CCK-8 assays and RT-PCR.The results reflected that the Ca2t released from nHA and NBC could bind chemically with collagen and affect its physicochemical properties,including the infrared absorption spectrum and compression modulus,among others.Furthermore,the two kinds of scaffolds could promote the expression of osteo-relative genes,but showed different gene induction properties.In short,NBC/CoL could promote the expression of early osteogenic genes,while nHA/CoL could upregulate late osteogenic genes.Conclusively,these two composite scaffolds could provide MC3T3-E1 cells with a biomimetic surface for adhesion,proliferation and the formation of mineralized extracellular matrices.Moreover,nHA/CoL and NBC/CoL had different effects on the period and extent ofMC3T3-E1 cell mineralization.

Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

Hydroxyapatite-containing PEO-coating design for biodegradable Mg-0.8Ca alloy: Formation and corrosion behaviour

In this study, the biocompatible protective coating was formed using plasma electrolytic oxidation(PEO) on bioresorbable Mg-0.8Ca alloy. The composition of the formed coating was studied using XRD, SEM-EDX analysis, and micro-Raman spectroscopy. The uniform distribution of hydroxyapatite over the thickness of protective PEO-layer was established. Using traditional(EIS, PDP, OCP) and local scanning electrochemical methods(SVET, SIET with H^(+)-selective microelectrode), the level of protective properties of PEO-layer in a biological environment(mammalian cell culture medium, MEM) was determined. It was established that modification of Mg-0.8Ca alloy surface by PEO contributes to a significant increase in the corrosion resistance of the surface layer, making it possible to control the process of material‘s biodegradation. The maximum local electrochemical activity was recorded after 72 h of testing, while for the uncoated sample,intense corrosion degradation was recorded in the first 12 min of exposure to the cell culture medium. Formation of the PEO-coating results in a twofold decrease in the corrosion current density(2.8·10^(-6)A cm^(-2)) and an increase in the impedance modulus measured at a low frequency(1.7·10^(4)Ω cm^(2)) in comparison with the uncoated material(9.5·10^(-6)A cm^(-2);8.1·10^(3)Ω cm^(2)). The mechanism of material bioresorption was established and a model for biodegradation process of Mg-0.8Ca alloy with hydroxyapatite-containing PEO-coating in MEM was proposed. Analysis of these results and comparing with others obtained by various scientific groups indicate the prospects for application of biocompatible PEO-coating on Mg-Ca alloy in implant surgery.

Corrosion behavior of composite coatings containing hydroxyapatite particles on Mg alloys by plasma electrolytic oxidation: A review

Mg and its alloys have been introduced as promising biodegradable materials for biomedical implant applications due to their excellent biocompatibility, mechanical behavior, and biodegradability. However, their susceptibility to rapid corrosion within the body poses a significant challenge and restricts their applications. To overcome this issue, various surface modification techniques have been developed to enhance the corrosion resistance and bioactivity of Mg-based implants. PEO is a potent technique for producing an oxide film on a surface that significantly minimizes the tendency to corrode. However, the inevitable defects due to discharges and poor biological activity during the coating process remain a concern. Therefore, adding suitable particles during the coating process is a suitable solution. Hydroxyapatite(HAp)has attracted much attention in the development of biomedical applications in the scientific community. HAp shows excellent biocompatibility due to its similarity in chemical composition to the mineral portion of bone. Therefore, its combination with Mg-based implants through PEO has shown significant improvements in their corrosion resistance and bioactivity. This review paper provides a comprehensive overview of the recent advances in the preparation, characterization, corrosion behavior and bioactivity applications of HAp particles on Mg-based implants by PEO.

The fabrication of hydroxyapatite mineralized hydrogels for bone tissue engineering

Bone is a complex but orderly mineralized tissue with hydroxyapatite(HA)as the inorganic phase and collagen as the organic phase.Inspired by natural bone tissues,HA-mineralized hydrogels have been widely designed and used in bone tissue engineering.HA is majorly utilized for the treatment of bone defects because of its excellent osteoconduction and bone inductivity.Hydrogel is a three-dimensional hydrophilic network structure with similar properties to the extracellular matrix(ECM).The combination of HA and hydrogels produces a new hybrid material that could effectively promote osteointegration and accelerate the healing of bone defects.In this review,the structure and growth of bone and the common strategies used to prepare HA were briefly introduced.Importantly,we discussed the fabrication of HA mineralized hydrogels from simple blending to in situ mineralization.We hope this review can provide a reference for the development of bone repair hydrogels.

Tissue Response and the Cytoconduction Ability to Collagen/Hydroxyapatite Heterotopic Implantation

A histological and ultrastructural observation of CHA implanted intra-muscularly and subcutaneously had been reported- Our results showed that a mildinflammation developed at the early stage and disappeared 2 weeks after implanta-tion. The infiltrating cells were mainly monocyte-macrophages, a number of fi-broblasts followed macrophags closely. It was possible that as CHA degrades,monocyte - mac rop hages continuouslyre leased inflammatory factors, thus enhanc-ing fibroblast proliferation activity and tissue regeneration. In addition, the het-erotopic calcification of collagen matrix was observed, suggesting that CHA prthmoted calcification deposition.

Electrospun Nanofibers of Hydroxyapatite / Collagen / Chitosan Promote Osteogenic Differentiation of BMSCs

Bone tissue engineering, aiming at developing bone substitutes for repair and regeneration of bone defects instead of using autologous bone grafts,has attracted wide attention in the field of tissue engineering and regenerative medicine.Developing biomimetic biomaterial scaffolds able to regulate osteogenic differentiation of stem cells could be a promising strategy to improve the therapeutic efficacy.In this study, electrospun composite nanofibers of hydroxyapatite / collagen / chitosan( HAp / Col / CTS)resembling the fibrous nanostructure and constituents of the hierarchically organized natural bone,were prepared to investigate their capacity for promoting bone mesenchymal stem cells( BMSCs)to differentiate into the osteogenic lineage in the absence and presence of the osteogenic supplementation, respectively.Cell morphology,proliferation and quantified specific osteogenic protein expression on the electrospun HAp / Col / CTS scaffolds were evaluated in comparison with different controls including electrospun nanofibrous CTS,HAp / CTS and tissue culture plate.Our results showed that the nanofibrous HAp / Col / CTS scaffolds supported better spreading and proliferation of the BMSCs than other substrates( P < 0.01).Expressions of osteogenesis protein markers,alkaline phosphatase( ALP) and Col,were significantly upregulated on the HAp / Col / CTS than those on the CTS( P < 0.01) and HAp /CTS( P < 0.05) scaffolds in the absence of the osteogenic supplementation.Moreover,presence of osteogenic supplementation also proved to enhance osteogenic differentiation of BMSCs on HAp /Col / CTS scaffolds, indicative of a synergistic effect.This study highlights the potential of BMSCs / HAp / Col / CTS cell-scaffold system for functional bone repair and regeneration applications.

Fabrication of Novel Scaffolds Containing Collagen-I/Polylactic Acid/Nanohydroxyapatite via Co-electrospinning Methods

A novel scaffold containing collagen-I/polylactic acid（PLA）/nanohydroxyapatite（nHA） was prepared via co-electrospinning method. Different target substrates were used to improve the collection efficiency of this scaffold. The properties of the novel scaffold were compared with those of conventionally prepared ones. Compared to con- ventional method, the modified method was more efficient in producing the scaffold. Moreover, the porosity, thickness, and morphology of the novel scaffold were better than those of scaffolds prepared by conventional methods. The properties of collagen-I, collagen-I/PLA and collagen-I/PLA/nHA scaffolds were also compared. Diameters of the electrospun fibers ranged from 180 to 405 nm, and roughness was present on the surface of the fibers due to the deposition of crystals of nHA along the long axis of the fibers. The fibers of the collagen-I/PLA/nHA scaffold and the fibers of natural bone tissue had similar structure.