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.

Hippo-YAP/TAZ signaling in osteogenesis and macrophage polarization:Therapeutic implications in bone defect repair

Bone defects caused by diseases or surgery are a common clinical problem.Researchers are devoted to finding biological mechanisms that accelerate bone defect repair,which is a complex and continuous process controlled by many factors.As members of transcriptional costimulatory molecules,Yes-associated protein(YAP)and transcriptional co-activator with PDZ-binding motif(TAZ)play an important regulatory role in osteogenesis,and they affect cell function by regulating the expression of osteogenic genes in osteogenesis-related cells.Macrophages are an important group of cells whose function is regulated by YAP/TAZ.Currently,the relationship between YAP/TAZ and macrophage polarization has attracted increasing attention.In bone tissue,YAP/TAZ can realize diverse osteogenic regulation by mediating macrophage polarization.Macrophages polarize into M1 and M2 phenotypes under different stimuli.M1 macrophages dominate the inflammatory response by releasing a number of inflammatory mediators in the early phase of bone defect repair,while massive aggregation of M2 macrophages is beneficial for inflammation resolution and tissue repair,as they secrete many anti-inflammatory and osteogenesis-related cytokines.The mechanism of YAP/TAZ-mediated macrophage polarization during osteogenesis warrants further study and it is likely to be a promising strategy for bone defect repair.In this article,we review the effect of Hippo-YAP/TAZ signaling and macrophage polarization on bone defect repair,and highlight the regulation of macrophage polarization by YAP/TAZ.

Biodegradable metals for bone defect repair:A systematic review and meta-analysis based on animal studies

Biodegradable metals are promising candidates for bone defect repair.With an evidence-based approach,this study investigated and analyzed the performance and degradation properties of biodegradable metals in animal models for bone defect repair to explore their potential clinical translation.Animal studies on bone defect repair with biodegradable metals in comparison with other traditional biomaterials were reviewed.Data was carefully collected after identification of population,intervention,comparison,outcome,and study design(PICOS),and following the inclusion criteria of biodegradable metals in animal studies.30 publications on pure Mg,Mg alloys,pure Zn and Zn alloys were finally included after extraction from a collected database of 2543 publications.A qualitative systematic review and a quantitative meta-analysis were performed.Given the heterogeneity in animal model,anatomical site and critical size defect(CSD),biodegradable metals exhibited mixed effects on bone defect repair and degradation in animal studies in comparison with traditional non-degradable metals,biodegradable polymers,bioceramics,and autogenous bone grafts.The results indicated that there were limitations in the experimental design of the included studies,and quality of the evidence presented by the studies was very low.To enhance clinical translation of biodegradable metals,evidence-based research with data validity is needed.Future studies should adopt standardized experimental protocols in investigating the effects of biodegradable metals on bone defect repair with animal models.

Large-sized bone defect repair by combining a decalcified bone matrix framework and bone regeneration units based on photo-crosslinkable osteogenic microgels

Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaffold,but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration.To address these problems,we proposed a novel strategy of bone regeneration units(BRUs)based on microgels produced by photo-crosslinkable and microfluidic techniques,containing both the osteogenic ingredient DBM and vascular endothelial growth factor(VEGF)for accurate biomimic of an osteoinductive microenvironment.The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.BRUs were successfully constructed by seeding BMSCs onto microgels,which achieved reliable bone regeneration in vivo.Finally,by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength,a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia.The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.

Bone Regeneration Enhanced by Antigen-Extracted Xenogeneic Cancellous Bone Graft with rhBMP-2 in Rabbits Mandibular Defect Repair

The effects of large piece xenogeneic bone which was separated from healthy pigs as a scaffold on repair of mandibular defect was investigated and the applicability of antigen-extracted xenogeneic cancellous bone (AXCB) soaked with rhBMP-2 in bone defect repair was assessed. Mandibular defects were created in 48 New Zealand Rabbits, and then randomly divided into 4 groups, which was grafted in the mandibular defects with AXCB, AXCB soaked with rhBMP-2, autograft bone, or blank. Equal number of animals from each group was classified into three time points (4, 8, and 12 weeks) after operation for gross pathological observation, hematoxylin and eosin (H & E) staining, radiographic examination, and bone density measurement. H & E staining revealed that the area percentage of bone regeneration in the group of AXCB/rhBMP-2 graft was 27.72 ± 4.68, 53.90 ± 21.92, and 77.35 ± 9.83 when at 4, 8, and 12 weeks, which was better than that of auto bone graft, prompting that the group of AXCB/rhBMP-2 graft had commendable osteogenic effect. And comparing with the AXCB without rhBMP-2, of which the area percentage of bone regeneration was only 14.03 ± 5.02, 28.49 ± 11.35, and 53.90 ± 21.92, the osteogenic effect of AXCB/rhBMP-2 graft was demonstrated to be much better. In the group of AXCB/rhBMP-2 graft, the area percentage of bone regeneration increased, and the implanted materials were gradually degraded and replaced by autogenous bone regeneration over time. We concluded that antigen-extracted xenogeneic cancellous bone (AXCB) graft soaked with rhBMP-2 had shown excellent osteogenic effect in repair of bone defects, with good biocompability.

One-Stage Repair and Reconstruction of Craniomaxillofacial Bone Defects

Objective: Severe craniomaxillofacial injuries and craniomaxillofacial tumors can lead to craniomaxillofacial bone defects and deformities. Seriously affect the patients’ appearance and quality of life. So one-stage repair and reconstruction of craniomaxillofacial bone defects is of great significance. The current study summarizes the clinical experience of one-stage repair and reconstruction of craniomaxillofacial bone defects. Material and Methods: Data in one-stage repair and reconstruction of?craniomaxillofacial bone defects performed on 13 patients were retrospectively analyzed out of 34 patients with?craniomaxillofacial injuries or tumors who received treatment at the outpatient department between January 2002 and March 2011. Surgical indications and approaches were explored after two typical cases were detected. Results: One-stage repair and reconstruction of bone defects was suitable for patients with craniomaxillofacial injuries and excised craniomaxillofacial benign tumors. Adjacent autogenous bones and artificial materials (such as titanium plates, titanium mesh, and so on) work well for the repair of the craniomaxillofacial bone frame and restoration of facial features. Conclusions: Surgical indications should be strictly selected in one-stage repair and reconstruction of craniomaxillofacial bone defects and deformities. Furthermore, the adoption of autogenous bones and artificial materials is a good choice in restoring the craniofacial features.

Role of transforming growth factor P and bone morphogenetic protein composite on repair of bone defects

Objective: To study the effect of transforming growth factor β/bone morphogenetic protein (TGFβ/BMP) composite on healing of large segmental bone defects and the interaction between TGF-β and BMP.Methods: A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adultrabbit. The defects were filled with implant of TGF-β/carrier, BMP/carrier and TGF-a/BMP/carrier, respectively. Purified bovine TGF-β 120 μg and BMP 12 mg were used in the composite. The defects were examined radiographically and histologically at 4, 8. 12 and 16 weeks post-operation (PO). Results: In groupof TGF-β/carrier, the defect areas were bridged at 4 weeks PO, with material of uniform radiodensity. Conices of the cut ends were obscured by the new bone. By 16 weeks PO, the defects were bridged by uniformnew bone and the cut ends of cortex could not be seen in all groups. In group of BMP/carrier, the defectswere filled with more irregular woven callus in comparison with the other two groups. The TGF-β/BMP--implanted defect sites in animals killed at 16 weeks PO showed histologically new larnellar and woven bone,formed in continuity with the cut ends of the cortex. The medullar cavity was recanalized and contained marrow elements with normal appearance. ConClUsion: These data demonstrate the synergistic action betweenTGF-β and BMP in the process of bone healing, and the better effect of TGF-β/BMP composite than that ofsingle TGF-β or BMP on bone repair.

Effect of low intensity pulsed ultrasound on repairing the periodontal bone of Beagle canines

Objective:To investigate the repairing effect of low intensity pulsed ultrasound(LIPUS)on the Beagle canines periodontal bone defect.Methods:A total of 12 Beagle dogs with periodontal bone defect model were randomly divided into control group,LIPUS group,guided tissue regeneration(GTR)group and LIPUS+GTR group,with three in each.After completion of the models,no other proceeding was performed in control group;LIPUS group adopt direct exposure to radiation line LIPUS processing 1 week after modeling;GTR group adopted treatment with GTR,following the CTR standard operation reference;LIPUS+GTR group was treated with LIPUS joint GTR.Temperature change before treatment and histopathological change of periodontal tissue after repair was observed.Results:There was no significant difference in temperature changes of periodontal tissue between groups(P>0.05).The amount and maturity of LIPUS+GTR group were superior to other groups;new cementum,dental periodontal bones of GTR group were superior to the control group but less than LIPUS group;new collagen and maturity of the control group is not high relatively.Conclusions:LIPUS can accelerate the calcium salt deposition and new bone maturation,thus it can serve as promoting periodontal tissue repair,and shortening the periodontal tissue repair time.

Guided bone regeneration in long-bone defect with a bilayer mineralized collagen membrane

Bone regeneration for large,critical-sized bone defects remains a clinical challenge nowadays.Guided bone regeneration(GBR)is a promising technique for the repair of multiple bone defects,which is widely used in oral and maxillofacial bone defects but is still unsatisfied in the treatment of long bone defects.Here,we successfully fabricated a bilayer mineralized collagen/collagen(MC/Col)-GBR membrane with excellent osteoinductive and barrier function by coating the MC particles prepared via in situ biomimetic mineralization process on one side of a sheet-like pure collagen layer.The aim of the present study was to investigate the physicochemical properties and biological functions of the MC/Col film,and to further evaluate its bone regeneration efficiency in large bone defect repair.Fouriertransform infrared spectra and X-ray diffraction patterns confirmed the presence of both hydroxyapatite and collagen phase in the MC/Col film,as well as the chemical interaction between them.stereo microscope,scanning electron microscopy and atomic force microscope showed the uniform distribution of MC particles in the MC/Col film,resulting in a rougher surface compared to the pure Col film.The quantitative analysis of surface contact angle,light transmittance and tensile strength demonstrated that the MC/Col film have better hydrophilicity,mechanical properties,light-barrier properties,respectively.In vitro macrophage co-culture experiments showed that the MC/Col film can effectively inhibit macrophage proliferation and fusion,reducing fibrous capsule formation.In vivo bone repair assessment of a rabbit critical segmental radial defect proved that the MC/Col film performed better than other groups in promoting bone repair and regeneration due to their unique dual osteoinductive/barrier function.These findings provided evidence that MC/Col film has a great clinical potential for effective bone defect repair.

Remote control of the recruitment and capture of endogenous stem cells by ultrasound for in situ repair of bone defects

Stem cell-based tissue engineering has provided a promising platform for repairing of bone defects.However,the use of exogenous bone marrow mesenchymal stem cells(BMSCs)still faces many challenges such as limited sources and potential risks.It is important to develop new approach to effectively recruit endogenous BMSCs and capture them for in situ bone regeneration.Here,we designed an acoustically responsive scaffold(ARS)and embedded it into SDF-1/BMP-2 loaded hydrogel to obtain biomimetic hydrogel scaffold complexes(BSC).The SDF-1/BMP-2 cytokines can be released on demand from the BSC implanted into the defected bone via pulsed ultrasound(p-US)irradiation at optimized acoustic parameters,recruiting the endogenous BMSCs to the bone defected or BSC site.Accompanied by the daily p-US irradiation for 14 days,the alginate hydrogel was degraded,resulting in the exposure of ARS to these recruited host stem cells.Then another set of sinusoidal continuous wave ultrasound(s-US)irradiation was applied to excite the ARS intrinsic resonance,forming highly localized acoustic field around its surface and generating enhanced acoustic trapping force,by which these recruited endogenous stem cells would be captured on the scaffold,greatly promoting them to adhesively grow for in situ bone tissue regeneration.Our study provides a novel and effective strategy for in situ bone defect repairing through acoustically manipulating endogenous BMSCs.

The influence of yttrium and manganese additions on the degradation and biocompatibility of magnesium-zinc-based alloys:In vitro and in vivo studies

The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone.The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration.In this study,we prepared and modified Mg-3Zn,Mg-3Zn-1Y,and Mg-2Zn-1Mn by hot extrusion,and used Mg-2.5Y-2.5Nd was as a control.We then investigated the effect of additions of Y and Mn on alloys'properties.Our results show that Mn and Y can improve not only compression strength but also corrosion resistance.The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro,and for this reason we selected it for implantation in vivo.The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction,and the degradation products left no signs of damage to the heart,liver,kidney,or brain.Furthermore,we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.

Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties,biocompatibility,biodegradability,vasculogenic ability and osteo-inductivity.The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma(PRP)-loaded gelatin methacrylate(GM)and employ them for the regeneration of large-sized bone defects.We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors(GFs)from hydrogels.The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects.For biofunction assay,the GM@PRP hydrogels significantly improved cell migration and angiogenesis.Especially,transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels.The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats.Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis,biomineralization,and collagen deposition.Based on the biocompatibility and biological function of GM@PRP hydrogels,a new strategy is provided for the regenerative repair of large-size bone defects.

Dual-response of multi-functional microsphere system to ultrasound and microenvironment for enhanced bone defect treatment

Using bone tissue engineering strategies to achieve bone defect repair is a promising modality.However,the repair process outcomes are often unsatisfactory.Here we properly designed a multi-functional microsphere system,which could deliver bioactive proteins under the dual response of ultrasound and microenvironment,release microenvironment-responsive products on demand,reverse bone injury microenvironment,regulate the immune microenvironment,and achieve excellent bone defect treatment outcomes.In particular,the MnO_(2) introduced into the poly(lactic-co-glycolic acid)(PLGA)microspheres during synthesis could consume the acid produced by the degradation of PLGA to protect bone morphogenetic protein-2(BMP-2).More importantly,MnO_(2) could consume reactive oxygen species(ROS)and produce Mn^(2+)and oxygen(O_(2)),further promoting the repair of bone defects while reversing the microenvironment.Moreover,the reversal of the bone injury microenvironment and the depletion of ROS promoted the polarization of M1 macrophages to M2 macrophages,and the immune microenvironment was regulated.Notably,the ultrasound(US)irradiation used during treatment also allowed the on-demand release of microenvironment-responsive products.The multi-functional microsphere system combines the effects of on-demand delivery,reversal of bone injury microenvironment,and regulation of the immune microenvironment,providing new horizons for the clinical application of protein delivery and bone defect repair.

可降解新型聚乳酸膜在引导骨组织再生中的应用

目的探索一种可降解新型聚乳酸膜(PDLLA/PLLA)在引导骨组织再生中的应用效果。方法新西兰大白兔24只,体重2.5~3.0 kg,在动物一侧下颌骨体部近下颌骨下缘处制备10 mm×5 mm×3 mm箱状骨缺损,然后将动物随机分为实验组、对照组和空白组,每组8只。实验组动物骨缺损处填Bio-oss骨粉后将PDLLA/PLLA覆盖于缺损表面,对照组动物骨缺损处填Bio-oss骨粉后将Guidor聚乳酸可吸收膜覆盖于缺损表面,空白组动物不作处理。术后8、12周采集缺损处标本,进行大体观察、Micro-CT检查和组织病理学观察。结果实验期间各组实验动物均未发生炎症和排异反应,各组创口愈合良好,成骨活跃。大体观察显示,术后8周实验组动物成骨量较多,材料降解较少,对照组动物成骨量较实验组少,材料降解完全;术后12周实验组动物和对照组动物成骨量相当,实验组材料进一步降解,空白组动物成骨量少于实验组和对照组。术后8、12周,Micro-CT可以观察到实验组和对照组缺损区域新生骨明显多于空白组。术后8、12周,实验组动物和对照组动物新生骨相对骨体积分数(BV/TV)、骨密度(BMD)和骨小梁数量(Tb.N)均显著高于空白组动物(P<0.05),且术后8周实验组动物新生骨BV/TV高于对照组(P<0.05);但在术后12周时实验组与对照组新生骨BV/TV、BMD和Tb.N比较,差异无统计学意义(P>0.05)。组织切片观察显示,术后8周实验组动物新生骨小梁周边细胞生长活跃,并可见少量成骨细胞及破骨细胞;术后12周实验组动物骨小梁周围可见大量成骨细胞及破骨细胞,骨缺损部位骨组织密度接近周边正常骨组织。结论与对照组和空白组相比,PDLLA/PLLA呈现出了良好的生物相容性和骨传导性,可以明显促进缺损处愈合。

中药有效成分结合骨组织工程材料用于骨修复

背景:如何修复骨缺损一直以来是临床难题,中药有效成分在骨修复方面具有良好的生物活性与治疗效果,将中药有效成分与组织工程材料相结合在骨修复领域具有广阔的前景。不同中药有效成分与支架的组合在作用关系方面具有相似之处。目的:搜集常见的中药有效成分与支架材料组合的案例,基于七情配伍的启发将组织工程支架与中药有效成分类比为产生配伍关系的两类中药,以二者的作用关系为纲进行归纳总结。方法:检索1998年1月至2024年1月Pub Med和中国知网数据库中发表的相关文献,英文检索词:“traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold”,中文检索词:“中药,中药有效成分,中药单体,骨组织工程,骨组织工程支架,支架,组织工程,骨缺损,骨修复”,最终纳入88篇文献进行综述分析。结果与结论:(1)组织工程支架材料与中药有效成分各自均在骨修复领域有广泛的运用,二者在成骨方面优势明显但仍有许多缺陷,许多研究致力于将二者制备成复合材料,希望通过二者间的相互作用发挥减毒增效作用。(2)一些药物与材料在成骨、抗菌、促血管生成方面能互相促进,增强原有的效果,受到传统方剂配伍观念的启发,文章将其归纳为“相须”关系,并举实例佐证。(3)一些药物能提高材料的强度,而某些材料能对负载于其上的药物实现缓释控释效果、增加载药量与稳定性,或是进行靶向递送,文章将这种单方面的提升效果归纳为“相使”关系。(4)一些中药与材料搭配使用能减少对方的毒副反应,文章将这种减毒关系归纳为“相畏相杀”。(5)文章得出了一个由七情配伍关系启发、基于作用关系分类的关于中药复合支架的全新视角,将中药传统观念引入组织工程领域,为后续复合支架的研究者提供新的研究思路,并在选材搭配方面提供一定的便利。

骨组织工程中研究水凝胶微球的特征

背景:水凝胶微球由于其多孔性和可注射性等在递送细胞和生物活性因子/药物、构建组织修复支架等生物医学领域展现独特优势,具有广阔的应用前景。目的:综述基于水凝胶微球的骨组织工程最新研究进展,讨论基于水凝胶微球的骨组织工程研究面临的关键问题和挑战。方法:应用计算机检索PubMed和中国知网数据库收录的相关文献。英文检索词为“hydrogels,microparticles,microspheres,microcarriers,bone,bone defect,bone repair,bone healing,bone tissue engineering”,中文检索词为“水凝胶,微球,微粒,骨组织工程,骨缺损,骨修复,骨再生”。检索文献时限为2002-2022年,最终纳入127篇文献进行综述。结果与结论:①目前,不同的水凝胶微球材料已被开发用于骨组织工程策略并取得了较好的效果,如搭载细胞或生物活性因子/药物的水凝胶微球、作为生物支架的水凝胶微球、刺激响应性水凝胶微球、生物矿化水凝胶微球、与其他生物材料结合的水凝胶微球等。②基于水凝胶微球的骨组织工程修复策略主要通过促进干细胞的招募与成骨分化、调节损伤局部炎症微环境以及促进损伤部位血管生成等机制来调控骨修复。但目前的研究没有深入探索基于水凝胶微球的骨组织工程诱导内源性干细胞招募与分化,以及水凝胶微球的理化性质对炎症微环境的调控,且水凝胶微球的体内长期不良反应尚未探明,批量生产存在困难,因此,未来的研究需要在机制探索和技术路线上加强深入,从而为开发能够用于临床转化的水凝胶微球材料提供合理参考。

纳米粒子在骨组织工程化基因修饰治疗中的应用

背景:传统的骨组织工程技术治疗临界骨缺损存在成骨效率低、安全性差等问题。而以非病毒纳米粒子为基因载体构建的基因强化型骨组织工程移植物,具有更高的成骨效率和安全性,引起了国内外学者的广泛关注和研究。目的:对当前国内外有关纳米粒子在组织工程成骨基因治疗研究中取得的新技术、新方法以及面临的挑战等进行综述,旨在为纳米粒子介导的骨组织工程基因治疗研究提供参考。方法:第一作者在Pub Med、Web of Science和中国知网数据库上进行文献检索,并以“Bone defect repair,Bone tissue engineering,Gene delivery,Nanoparticles,Non-viral gene vector,Sustained release technology,Sequential release,Targeted delivery”作为英文检索词,以“骨缺损修复,骨组织工程,基因递送,纳米粒子,非病毒基因载体,缓释技术,序贯释放,靶向递送”作为中文检索词,最终纳入84篇文献进行总结。结果与结论:(1)在骨缺损愈合的各个生理阶段进行针对性的基因递送可以显著增强骨修复效果。在早期炎症阶段,通过纳米粒子递送抗炎基因来调节炎症反应,可以为后续骨愈合奠定基础;在血管新生期,向局部递送促血管化基因有助于形成高度组织化、可灌注的血管系统,加快骨愈合速度;随着血管化的进行,骨骼的神经再支配也开始发生,此时递送促神经再生的功能性基因有利于促进神经化骨再生;在成骨阶段,通过构建纳米粒子-成骨基因复合物,可以直接提升支架及体内新骨形成的效率。(2)各种有机、无机纳米颗粒、金属有机框架和外泌体等非病毒纳米载体,在骨组织工程基因治疗中具有巨大的潜力,这些纳米基因载体各有其独特的优势和不足,因此在实际应用时,需要根据基因转染效率、生物安全性和成骨特性等因素选择最合适的类型。(3)为了全面提升递送基因的效果,目前主要通过对纳米载体进行各种功能设计来增强基因转染效率,包括增强缓释性和多基因递送序贯性等时间调控能力、增强对骨组织和成骨相关细胞的空间靶向能力、增强跨膜运输效率和细胞核靶向能力等全过程调控手段。(4)未来要进一步推动纳米粒子介导的骨组织工程基因治疗在临床上的应用,还需要克服诸多技术挑战,包括提高有机纳米基因载体的基因转染效率、降低无机纳米载体的生物安全性风险、优化新型纳米载体的生产工艺以及促进其它生理过程与成骨交互作用等,这些问题也是未来骨组织工程基因治疗的研究热点和潮流。

金属离子在骨组织工程中的应用

背景:金属离子在人体中发挥着重要的作用,随着材料合成和加工技术的进步,目前多种可应用于骨组织工程中的金属离子已被开发,如镁(Mg2+)、锌(Zn2+)、锰(Mn2+)、锶(Sr2+)、铜(Cu2+)等。目的:总结各金属离子在骨组织工程中的研究进展和发展方向。方法:检索2014-2022年期间中国知网数据库、PubMed数据库、万方数据库收录的文献,中文检索词为“金属离子,骨组织工程,成骨活性,镁离子,锌离子,锰离子,锶离子,铜离子,钙离子,锂离子,钴离子”,英文检索词为“metal ions,bone tissue engineering,osteogenic activity,magnesium ions,zinc ions,manganese ions,strontium ions,copper ions,calcium ions,lithium ions,cobalt ions”。结果与结论:不同金属离子随材料植入体内后会发生不同程度的释放,可改变组织微环境,从而改善材料成血管、成骨的能力。与生长因子相比,金属离子更易控制释放速率,且成本更低,还能够改善植入材料力学性能。金属离子在骨组织工程中的应用充满前景,虽然部分金属离子已经可以用于治疗骨缺损,但许多金属离子在人体内的作用机制尚未完全明确、应用效果缺少临床试验验证,投入临床应用前还需进一步探索。

高模量高强度丝素蛋白GBR膜的制备及性能评估

目的拟制备一种高模量和高强度的可降解丝素蛋白引导骨再生(GBR)膜,以解决骨缺损修复成骨空间维持问题。方法提纯丝素蛋白后利用蒸发-热压法制备膜材,使用拉伸测试、体外模拟、细胞共培养等方法评估其理化性质与生物性能。结果制得丝素蛋白GBR膜,体外模拟12 h降解率为35.3%,湿态弹性模量达45 MPa,拉伸强度达8.39 MPa,7 d细胞生存率近100%。结论所制得可降解GBR膜具有高模量和高强度,以及优异的生物相容性,有望为解决骨缺损修复成骨空间维持问题提供材料基础。