Exploring the interconnectivity of biomimetic hierarchical porous Mg scaffolds for bone tissue engineering:Effects of pore size distribution on mechanical properties,degradation behavior and cell migration ability

Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.

Experimental Study of Porous Beta-tricalcium Phosphate and Bone Morphogenetic Protein/porous Beta-tricalcium Phosphate Complex in Rabbit Mandibular Reconstruction

We investigated the osteogenic characteristic and biodegradation behavior of porous beta-tricalcitum phosphate （ β- TCP ） and bone morphogenetic protein/beta-tricalcium phosphate （ BMP/ β- TCP ） complex in mandibular reconstruction and evaluated the advantages of BMP / β- TCP complex in repairing bone defects. Bone defects created in the lower margin of bilateral mandible bodies in 12 rabbits were repaired with β- TCP （ control group ） and BMP/ β- TCP complex （ experimental group ） respectively. The rabbits were euthanized after 2, 4, 8 and 12 weeks and examined by macroscopy, radiography, histology, histomorphometry and image analysis. 2 weeks after surgery, ossftcation of newly-generated tissue in BMP/ β- TCP complex group appeared and after 12 weeks, massive new bone and ossification maturation were seen. However, in β- TCP group without BMP , ossification was not found until 12 weeks after operation. Image analysis showed that bone regeneration rate of BMP/ β- TCP was 30%-40% higher and the degradation rate was 20%- 30% higher than that of β- TCP. Therefore, as a reconstructive material for bone defects, BMP/ β-TCP complex is superior to β-TCP and can be used in oral and maxillofacial surgery.

Design and Preparation of Bone Tissue Engineering Scaffolds with Porous Controllable Structure

A novel method of designing and preparing bone tissue engineering scaffolds with controllable porous structure of both macro channels and micro pores was proposed. The CAD software UG NX3.0 was used to design the macro channels＇ shape, size and distribution. By integrating rapid prototyping and traditional porogen technique, the macro channels and micro pores were formed respectively. The size, shape and quantity of micro pores were controlled by porogen particulates. The sintered β-TCP porous scaffolds possessed connective macro channels of approximately 500 μm and micro pores of 200-400 μm. The porosity and connectivity of micro pores became higher with the increase of porogen ratio, while the mechanical properties weakened. The average porosity and compressive strength offl-TCP scaffolds prepared with porogen ratio of 60wt% were 78.12% and 0.2983 MPa, respectively. The cells＇ adhesion ratio of scaffolds was 67.43%. The ALP activity, OCN content and cells micro morphology indicated that cells grew and proliferated well on the scaffolds.

Mechanically strong porous bioceramic tubes facilitate large segmental bone defect repair by providing long-term structurally stability and promoting osteogenesis

Mechanically strong magnesium-doped Ca-silicate bioceramic scaffolds have many advantages in repairing large segmental bone defects.Herein we combine β-TCP with 6 mol%magnesium-doped calcium silicate(Mg6)at three different ratios(TCP,TCP+15%Mg6,TCP+85%Mg6)to find an appropriate ratio which can exert considerable influence on bone regeneration.In this study,the bioceramic scaffolds were assessed for mechanical strength,bioactive ion release,biocompatibility,and osteogenic capacity through in vitro testing.Additionally,the potential for promoting bone regeneration was investigated through in vivo implantation of porous tube-like scaffolds.The results showed that the compressive strength increased with the augmentation of Mg6 component.Especially the compressive strength of the TCP+85%Mg6 group reached 38.1±3.8 MPa,three times that of the other two groups.Furthermore,extensive in vivo investigations revealed that the TCP+85%Mg6 bioceramic scaffolds were particularly beneficial for the osteogenic capacity of critical-sized femoral defects(20 mm in length).Altogether,magnesium doping in bioceramic implants is a promising strategy to provide stronger mechanical support and enhance osteogenesis to accelerate the repair of large defects.

Phosphate Glass Fibre Composites for Bone Repair

We investigate high-modulus degradable materials intended to replace metals in biomedical applications.These are typically composites comprising a polylactide(PLA)matrix reinforced with phosphate glass fibres,which provide reinforcement similar to E-glass but are entirely degradable in water to produce,principally,calcium phosphate.We have made composites using a variety of fibre architectures,from non-woven random mats to unidirectional fibre tapes.Flexural properties in the region of 30 GPa modulus and 350 MPa strength have been achieved-directly comparable to quoted values for human cortical bone.In collaboration with other groups we have begun to consider the development of foamed systems with structures mimicking cancellous bone and this has shown significant promise.The fibres in these foamed structures provide improved creep resistance and reinforcement of the pore walls.To date the materials have exhibited excellent cellular responses in vitro and further studies are due to include consideration of the surface character of the materials and the influence of this on cell interaction, both with the composites and the glass fibres themselves,which show promise as a standalone porous scaffold.

Design and Simulation of Flow Field for Bone Tissue Engineering Sca old Based on Triply Periodic Minimal Surface

A novel method was proposed to design the structure of a bone tissue engineering scafold based on triply periodic minimal surface.In this method,reverse engineering software was used to reconstruct the surface from point cloud data.This method overcomes the limitations of commercially available software packages that prevent them from generating models with complex surfaces used for bone tissue engineering scafolds.Additionally,the fluid feld of the scafolds was simulated through a numerical method based on fnite volume and the cell proliferation performance was evaluated via an in vitro experiment.The cell proliferation and the mass flow evaluated in a bioreactor further verifed the flow feld simulated using computational fluid dynamics.The result of this study illustrates that the pressure value drops rapidly from 0.103 Pa to 0.011 Pa in the y-axis direction and the mass flow is unevenly distributed in the outlets.The mass flow in the side outlets is observed to be approximately 24.3 times higher thanthe bottom.Importantly,although the mean value of wall shear stress is signifcantly more than 0.05 Pa,there is stil a large area with a suitable shear stress below 0.05 Pa where most cells can proliferate well.The result shows that th inlet velocity 0.0075 m/s is suitable for cell proliferation in the scafold.This study provides an insight into the design analysis,and in vitro experiment of a bone tissue engineering scafold.

Acetabular revisions using porous tantalum components: A retrospective study with 5-10 years follow-up

AIM To evaluate the clinical and X-ray results of acetabular components and tantalum augments in prosthetic hip revisions.METHODS Fifty-eight hip prostheses with primary failure of the acetabular component were reviewed with tantalum implants. The clinical records and X-rays of these cases were retrospectively reviewed. Bone defect evaluations were based on preoperative CT scans and classified according to Paprosky criteria of Radiolucent lines and periprosthetic gaps; implant mobilization and osteolysis were evaluated by X-ray. An ad hoc database was created and statistical analyses were performed with SPSS software(IBM SPSS Statistics for Windows, version 23.0). Statistical analyses were carried out using the Student's t test for independent and paired samples. A P value of < 0.05 was considered statistically significant and cumulative survival was calculated by the KaplanMeier method.RESULTS The mean follow-up was 87.6 ± 25.6 mo(range 3-120 mo). 25 cases(43.1%) were classified as minor defects, and 33 cases(56.9%) as major defects. The preoperative HHS rating improved significantly from a mean of 40.7 ± 6.1(range: 29-53) before revision, to a mean of 85.8 ± 6.1(range: 70-94) at the end of the follow-up(Student's t test for paired samples: P < 0.001). Considering HHS only at the end of follow-up, no statistically significant difference was observed between patients with a major or minor defect(Student's t test for independent samples: P > 0.05). Radiolucent lines were found in 4 implants(6.9%). Postoperative acetabular gaps were observed in 5 hips(8.6%). No signs of implant mobilization or areas of periprosthetic osteolysis were found in the x-rays at the final follow-up. Only 3 implants failed: 1 case of infection and 2 cases of instability. Defined as the end-point, cumulative survival at 10 years was 95%(for all reasons) and 100% for aseptic loosening of the acetabular component.CONCLUSION The medium-term use of prosthetic tantalum components in prosthetic hip revisions is safe and effective in a wide variety of acetabular bone defects.

Mechanical Experiment for 3D Printing of Titanium Bone Bionic Dental Implants

[Objectives] To explore the flexural strength of 3D printed titanium bone bionic dental implants and provide a scientific basis for the clinical application of 3D printed porous bionic bone dental implants. [Methods] The cone-beam CT( CBCT) image information of 20 premolars extracted by orthodontic requirement was collected,and a new porous bone bionic dental implant was produced using modeling software and 3D printer. The premolars were divided into two groups( A and B). The universal testing machine was used to test the flexural strength of the two groups and the difference in flexural strength between the two groups was compared through statistics. [Results]Twenty 3D printed porous titanium bone bionic implants were accurately produced; the morphology of group A and group B were extremely similar to each other; the average flexural strength of group A was 2 767. 92 N,while the average flexural strength of group B was 778. 77 N,showing that the average flexural strength of group A was significantly higher than that of group B,and the difference was statistically significant( P < 0. 05).[Conclusions]The personalized porous structure root implants produced by 3D printing technology are very similar to the target tooth morphology,and show high accuracy and small error of production. Besides,the flexural strength of 3D printed personalized porous structure root implants can fully meet the requirements of the maximum occlusal force for dental implant restoration. It is expected to provide a scientific basis for clinical application of 3 D printed porous bionic bone tooth implants.

A drug-loaded composite coating to improve osteogenic and antibacterial properties of Zn-1Mg porous scaffolds as biodegradable bone implants

Zinc(Zn)alloy porous scaffolds produced by additive manufacturing own customizable structures and biodegradable functions,having a great application potential for repairing bone defect.In this work,a hydroxyapatite(HA)/polydopamine(PDA)composite coating was constructed on the surface of Zn-1Mg porous scaffolds fabricated by laser powder bed fusion,and was loaded with a bioactive factor BMP2 and an antibacterial drug vancomycin.The microstructure,degradation behavior,biocompatibility,antibacterial performance and osteogenic activities were systematically investigated.Compared with as-built Zn-1Mg scaffolds,the rapid increase of Zn2+,which resulted to the deteriorated cell viability and osteogenic differentiation,was inhibited due to the physical barrier of the composite coating.In vitro cellular and bacterial assay indicated that the loaded BMP2 and vancomycin considerably enhanced the cytocompatibility and antibacterial performance.Significantly improved osteogenic and antibacterial functions were also observed according to in vivo implantation in the lateral femoral condyle of rats.The design,influence and mechanism of the composite coating were discussed accordingly.It was concluded that the additively manufactured Zn-1Mg porous scaffolds together with the composite coating could modulate biodegradable performance and contribute to effective promotion of bone recovery and antibacterial function.

Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K/AKT/mTOR signaling pathways and facilitated bone regeneration in vivo

The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essential conditions for bone regeneration.Meanwhile,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis.However,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp.Hence in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were explored.The results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene expression.Further-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions.The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic scaffolds.Besides,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358.In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality.These results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.

Functionalize d 3D-printe d porous titanium scaffold induces in situ vascularized bone regeneration by orchestrating bone microenvironment

Titanium(Ti)and its alloys have been extensively explored for treating load-bearing bone defects.How-ever,high-stress shielding,weak osteogenic activity,and insufficient vascularization remain key chal-lenges for the long-term clinical outcomes of Ti-based implants.Herein,inspired by structural and func-tional cues of bone regeneration,a silicon-doped nano-hydroxyapatite(nSiHA)/titanium dioxide(TiO_(2))composite coating with a hierarchical micro/nano-network structure is constructed on the surface of a 3D-printed porous Ti scaffold via a combined strategy of acid-alkali(AA)treatment and electrochemi-cal deposition technique,which not only endows the scaffold with excellent osteoinduction ability but can also effectively immobilize and release vascular endothelial growth factor(VEGF).The results of the in vitro cell experiments show that the functionalized Ti scaffold significantly promotes osteogenesis in bone marrow mesenchymal stem cells(BMSCs)and angiogenesis in human umbilical vein endothelial cells(HUVECs)by activating the extracellular signal-regulated protein kinase(ERK)and HIF-1αsignaling pathways.After being implanted into a rat femoral condyle defect model,the functionalized Ti scaffold can induce in situ vascularized bone regeneration by orchestrating the two coupled processes of angio-genesis and osteogenesis.These findings indicate that the functionalized Ti scaffold has great potential in bone tissue regeneration and is a promising candidate for load-bearing bone defect repair.

Biodegradable porous Zn-1Mg-3βTCP scaffold for bone defect repair:In vitro and in vivo evaluation

Zn-based materials are promising as bone repair materials,but their poor mechanical property and bioactivity as well as low degradation rate render the potential application.Rational structural and material design can address the concerns.In this study,porous Zn-1 wt.%Mg-3 vol.%β-TCP scaffolds with 40%and 60%preset porosities were fabricated via heating-press sintering using NaCl particles as space holders,and their mechanical properties,in vitro degradation behavior,cytotoxicity and in vivo osteogenic activities were evaluated.The results showed that the actual porosities of the scaffolds were 22%and 50%.Mg exists in the form of Zn 2 Mg and Zn 11 Mg 2,whileβ-TCP evenly distributed in the matrix.The compressive yield strength of scaffolds ranges from approximately 58.46 to 71.04 MPa,which is close to that of cancellous bone.The in vitro degradation tests showed that the corrosion rate of the scaffolds was in the range of about 2.73-4.28 mm y^(-1).Moreover,the scaffolds not only provided great space for osteoblasts adhesion and proliferation in vitro but also possessed favorable degradability and osteogenic activity in vivo.The porous Zn-1 wt.%Mg-3 vol.%β-TCP scaffolds manifest reliable mechanical properties,desirable degradability,and osteogenic activity,which are promising as next-generation bone repair materials.

Design,characterisation,and clinical evaluation of a novel porous Ti-6Al-4V hemipelvic prosthesis based on Voronoi diagram

Three-dimensional printed Ti-6Al-4V hemipelvic prosthesis has become a current popular method for pelvic defect reconstruction.This paper presents a novel biomimetic hemipelvic prosthesis design that utilises patient-specific anatomical data in conjunction with the Voronoi diagram algorithm.Unlike traditional design methods that rely on fixed,homogeneous unit cell,the Voronoi diagram enables to create imitation of trabecular structure(ITS).The proposed approach was conducted for six patients.The entire contour of the customised prosthesis matched well with the residual bone.The porosity and pore size of the ITS were evaluated.The distribution of the pore size ranged from 500 to 1400μm.Porosity calculations indicated the average porosity was 63.13±0.30%.Cubic ITS samples were fabricated for micrograph and mechanical analysis.Scanning electron microscopy images of the ITS samples exhibited rough surface morphology without obvious defects.The Young’s modulus and compressive strength were 1.68±0.05 GPa and 174±8 MPa,respectively.Post-operative X-rays confirmed proper matching of the customised prostheses with the bone defect.Tomosynthesis-Shimadzu metal artifact reduction technology images indicated close contact between the implant and host bone,alongside favourable bone density and absence of resorption or osteolysis around the implant.At the last follow-up,the average Musculoskeletal Tumour Society score was 23.2(range,21-26).By leveraging additive manufacturing and Voronoi diagram algorithm,customised implants tailored to individual patient anatomy can be fabricated,offering wide distribution of the pore size,reasonable mechanical properties,favourable osseointegration,and satisfactory function.

三种骨替代材料修复即刻种植下颌后牙区周围骨缺损的比较

背景:引导骨再生技术是解决种植区域骨缺损的有效方法,但是选择何种骨替代材料尚存有一定争议。目的:探讨不同材料应用于即刻种植下颌后牙区周围骨缺损的治疗效果。方法:选择2016年5月至2019年1月北京大学人民医院口腔科收治的138例下颌后牙区周围骨缺损患者,采用随机数字表法分3组,在即刻种植手术中分别植入Bio-Oss、Bone Plant、PerioGlas骨替代材料,每组46例。术后定期随访,比较3组种植体成功率、边缘骨水平、颊舌侧骨板宽度、垂直高度、牙周指标及患者满意度。研究获得北京大学人民医院伦理委员会批准,批准号:[伦审(R20160412)]。结果与结论:①术后12个月时,Bone Plant组种植体成功率高于PerioGlas组(P<0.05),其余组间两两比较差异无显著性意义(P>0.05);②Bio-Oss组、Bone Plant组术后6,12个月的边缘骨水平低于PerioGlas组(P<0.05),颊舌侧骨板宽度、垂直高度高于PerioGlas组(P<0.05);Bone Plant组术后6,12个月的垂直高度高于Bio-Oss组(P<0.05),两组间边缘骨水平、颊舌侧骨板宽度比较差异无显著性意义(P>0.05);③术后6,12个月时,3组间牙周探诊深度、探诊出血阳性率、牙龈指数比较差异均无显著性意义(P>0.05);④3组间患者满意度比较差异无显著性意义(P>0.05);⑤结果表明,Bio-Oss、PerioGlas、Bone Plant均具有一定诱导骨再生和成骨效果,Bio-Oss吸收慢但可维持一定骨板宽度,Bone Plant维持骨缺损垂直高度和空间稳定效果好,是较为理想的骨替代材料。

Three-dimensional-printed individualized porous implants:A new“implant-bone”interface fusion concept for large bone defect treatment

Bone defect repairs are based on bone graft fusion or replacement.Current large bone defect treatments are inadequate and lack of reliable technology.Therefore,we aimed to investigate a simple technique using three-dimensional(3D)-printed individualized porous implants without any bone grafts,osteoinductive agents,or surface biofunctionalization to treat large bone defects,and systematically study its long-term therapeutic effects and osseointegration characteristics.Twenty-six patients with large bone defects caused by tumor,infection,or trauma received treatment with individualized porous implants;among them,three typical cases underwent a detailed study.Additionally,a large segmental femur defect sheep model was used to study the osseointegration characteristics.Immediate and long-term biomechanical stability was achieved,and the animal study revealed that the bone grew into the pores with gradual remodeling,resulting in a long-term mechanically stable implant-bone complex.Advantages of 3D-printed microporous implants for the repair of bone defects included 1)that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility,and 2)that osseointegration between the host bone and implants was achieved without bone grafting.Our osseointegration method,in which the“implant-bone”interface fusion concept was used instead of“bone-bone”fusion,subverts the traditional idea of osseointegration.

Experimental study of a 3D printed permanent implantable porous Ta-coated bone plate for fracture fixation

Metal plates have always been the gold standard in the clinic for internal fracture fixation due to their high strength advantages.However,high elastic modulus can cause stress shielding and lead to bone embrittlement.This study used an electron beam melting method to prepare personalized porous Ti6Al4V(pTi)bone plates.Then,chemical vapor deposition(CVD)technology coats tantalum(Ta)metal on the pTi bone plates.The prepared porous Ta-coated bone plate has an elastic modulus similar to cortical bone,and no stress shielding occurred.In vitro experiments showed that compared with pTi plates,Ta coating significantly enhances the attachment and proliferation of cells on the surface of the scaffold.To better evaluate the function of the Ta-coated bone plate,animal experiments were conducted using a coat tibia fracture model.Our results showed that the Ta-coated bone plate could effectively fix the fracture.Both imaging and histological analysis showed that the Ta-coated bone plate had prominent indirect binding of callus formation.Histological results showed that new bone grew at the interface and formed good osseointegration with the host bone.Therefore,this study provides an alternative to bio-functional Ta-coated bone plates with improved osseointegration and osteogenic functions for orthopaedic applications.

Porous silicon carbide coated with tantalum as potential material for bone implants

Porous silicon carbide(SiC)has a specific biomorphous microstructure similar to the trabecular microstructure of human bone.Compared with that of bioactive ceramics,such as calcium phosphate,SiC does not induce spontaneous interface bonding to living bone.In this study,bioactive tantalum(Ta)metal deposited on porous SiC scaffolds by chemical vapour deposition was investigated to accelerate osseointegration and improve the bonding to bones.Scanning electron microscopy indicated that the Ta coating evenly covered the entire scaffold structure.Energy-dispersive spectroscopy and X-ray diffraction analysis showed that the coating consisted of Ta phases.The bonding strength between the Ta coating and the SiC substrate is 88.4MPa.The yield strength of porous SiC with a Ta coating(pTa)was 45.862.9MPa,the compressive strength was 61.463.2MPa and the elasticmodulus was4.8GPa.When MG-63 human osteoblasts were co-cultured with pTa,osteoblasts showed good adhesion and spreading on the surface of the pTa and its porous structure,which showed that it has excellent bioactivity and cyto-compatibility.To further study the osseointegration properties of pTa.PTa and porous titanium(pTi)were implanted into the femoral neck of goats for 12weeks,respectively.The Van-Gieson staining of histological sections results that the pTa group had better osseointegration than the pTi group.These results indicate that coating bioactive Ta metal on porous SiC scaffolds could be a potential material for bone substitutes.

Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration

Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes and ineffective delivery method,are still persisted.Here,we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth(SHEDs)via comprehensive proteomics analysis,and the corresponding hypoxic exosomes(H-Exo)exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion,VEGF signaling pathway,and thyroid hormone synthesis.Then,we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection.This platform is based on a simple adsorbing technique,where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide)(PLGA)microspheres with bioinspired polydopamine(PDA)coating(PMS-PDA microspheres).The PMS-PDA microspheres could effectively adsorb exosomes,show sustained release of H-Exo for 21 days with high bioactivity,and induce vascularized bone regeneration in 5-mm rat calvarial defect.These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration,hence facilitating the clinical translation of exosome-based therapy.

Porous polyetheretherketone microcarriers fabricated via hydroxylation together with cellderived mineralized extracellular matrix coatings promote cell expansion and bone regeneration

Porous microcarriers have aroused increasing attention recently by facilitating oxygen and nutrient transfer,supporting cell attachment and growth with sufficient cell seeding density.In this study,porous polyetheretherketone(PEEK)microcarriers coated with mineralized extracellular matrix(mECM),known for their chemical,mechanical and biological superiority,were developed for orthopedic applications.Porous PEEK microcarriers were derived from smooth microcarriers using a simple wet-chemistry strategy involving the reduction of carbonyl groups.This treatment simultaneously modified surface topology and chemical composition.Furthermore,the microstructure,protein absorption,cytotoxicity and bioactivity of the obtained porous microcarriers were investigated.The deposition of mECM through repeated recellularization and decellularization on the surface of porous MCs further promoted cell proliferation and osteogenic activity.Additionally,the mECM coated porous microcarriers exhibited excellent bone regeneration in a rat calvarial defect repair model in vivo,suggesting huge potential applications in bone tissue engineering.

Polyhydroxybutyrate/Hydroxyapatite Highly Porous Scaffold for Small Bone Defects Replacement in the Nonload-bearing Parts

In the present work, Polyhydroxybutyrate （PHB）/Hydroxyapatite （HA） porous composites （10%, 20%, 30 %, 40%, 50% weight HA） were obtained by sintering. PHB/20% HA optimally combines satisfactory mechanical properties with a high content of the bioactive component （HA）. Porous PHB/20% HA scaffolds have shown high mechanical properties （compressive strength of 106 MPa and Young＇s modulus of 901 MPa）. A high volume fraction of interconnected pores （〉 50 vol.%） was achieved with pore size of 50 grn - 500 gm. Biocompatibility of porous pure PHB and PHB/20%HA, as its osseointegration were assessed in vitro and after implantation in laboratory animals. PHB/20% HA （-5% ＋ 0.9%） and pure PHB ~3% ~ 1.4%） samples after 24 hours of incubation with human leucocytes showed no significant level of cytotoxicity when p = 0.648 （p-value）. In vitro massive adhesion of mouse Multipotent Mesenchymal Stromal Cells （MMSC） to the surface of both porous samples was shown. PHB/20% HA induced more intensive MMSC proliferation compared to pure PHB, which are 31% ＋ 6.1% and 20% ＋ 5.7 % respectively when p = 0.039. We observed the resorption （implant surface area was reduced by 49 %） and integration of the porous PHB/20% HA samples into surrounding tissues after 30 days of implantation. The signs of osteoclasts accumulation, neo-angigenesis and new bone formation were observed, which make PHB/20% HA promising for bone tissue engineering.