Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury

Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique.

Biomimetic chitosan scaffolds with long-term controlled release of nerve growth factor repairs 20-mm-long sciatic nerve defects in rats

Although autogenous nerve transplantation is the gold standard for treating peripheral nerve defects of considerable length,it still has some shortcomings,such as insufficient donors and secondary injury.Composite chitosan scaffolds loaded with controlled release of nerve growth factor can promote neuronal survival and axonal regeneration after short-segment sciatic nerve defects.However,the effects on extended nerve defects remain poorly understood.In this study,we used chitosan scaffolds loaded with nerve growth factor for 8 weeks to repair long-segment(20 mm)sciatic nerve defects in adult rats.The results showed that treatment markedly promoted the recovery of motor and sensory functions.The regenerated sciatic nerve not only reconnected with neurons but neural circuits with the central nervous system were also reconstructed.In addition,the regenerated sciatic nerve reconnected the motor endplate with the target muscle.Therefore,this novel biomimetic scaffold can promote the regeneration of extended sciatic nerve defects and reconstruct functional circuits.This provides a promising method for the clinical treatment of extended peripheral nerve injury.This study was approved by the Animal Ethics Committee of Capital Medical University,China(approval No.AEEI-2017-033)on March 21,2017.

A partition-type tubular scaffold loaded with PDGF-releasing microspheres for spinal cord repair facilitates the directional migration and growth of cells

The best tissue-engineered spinal cord grafts not only match the structural characteristics of the spinal cord but also allow the seed cells to grow and function in situ.Platelet-derived growth factor（PDGF） has been shown to promote the migration of bone marrow stromal cells;however,cytokines need to be released at a steady rate to maintain a stable concentration in vivo.Therefore,new methods are needed to maintain an optimal concentration of cytokines over an extended period of time to effectively promote seed cell localization,proliferation and differentiation.In the present study,a partition-type tubular scaffold matching the anatomical features of the thoracic 8–10 spinal cord of the rat was fabricated using chitosan and then subsequently loaded with chitosan-encapsulated PDGF-BB microspheres（PDGF-MSs）.The PDGF-MS-containing scaffold was then examined in vitro for sustained-release capacity,biocompatibility,and its effect on neural progenitor cells differentiated in vitro from multilineage-differentiating stress-enduring cells（MUSE-NPCs）.We found that pre-freezing for 2 hours at-20°C significantly increased the yield of partition-type tubular scaffolds,and 30 μL of 25% glutaraldehyde ensured optimal crosslinking of PDGF-MSs.The resulting PDGF-MSs cumulatively released 52% of the PDGF-BB at 4 weeks in vitro without burst release.The PDGF-MS-containing tubular scaffold showed suitable biocompatibility towards MUSE-NPCs and could promote the directional migration and growth of these cells.These findings indicate that the combination of a partition-type tubular scaffold,PDGF-MSs and MUSENPCs may be a promising model for the fabrication of tissue-engineered spinal cord grafts.

血管生成相关生长因子促进创口愈合的研究进展

在创口愈合过程中,血管生成是组织修复的起始和关键,新生血管可为组织输送所需的氧气、细胞及营养,同时带走代谢废物。在血管生成过程中,相关生长因子起到至关重要的作用。作为优异的输送载体,支架材料在生物递送和组织再生方面具有显著成效,有望使生长因子成为加速创口愈合的重要治疗靶点。综述了创口愈合中血管生成过程、血管生成相关生长因子的作用及其在组织工程中的应用。

食管组织工程:研究、应用与展望

食管作为人体消化系统的重要组成部分,其损伤与疾病严重影响着患者的健康与生活质量。近年来,组织工程技术在食管修复和重建中取得显著进展。本文旨在探讨食管组织工程在食管损伤修复和重建中的应用研究,以应对传统食管替代术带来的高并发症风险。本文综述了支架材料、种子细胞、生长因子等关键要素在组织工程食管构建中的一些最新研究进展,并总结了组织工程技术在内镜黏膜下剥离术后食管修复中的应用情况。最后,本文讨论了食管组织工程面临的挑战与未来研究方向,以期为食管组织工程的发展及转化提供参考。

5个梨树品种在荆门棚架栽培的适应性调查研究

【目的】调查分析不同梨树品种在荆门地区棚架栽培的适应性,以期为荆门市梨树棚架栽培提供参考依据。【方法】以‘苏翠1号’‘翠冠’‘圆黄’‘翠玉’‘鄂梨2号’5个梨树品种为试验材料,调查其在荆门地区定植后1~3年棚架生长的适应性。【结果】‘苏翠1号’‘鄂梨2号’无论是在生长势还是枝条数量上均表现出相对优势,第3年主干粗度、双臂长度与粗度、侧枝生长量均高于各品种平均水平,棚架上架率达到90%及以上,比较适宜棚架栽培。‘翠玉’与‘圆黄’梨相对树势较弱,第3年侧枝生长量及相关指标不达标,棚架上架率不到80%。‘翠冠’品种表现良好,棚架上架率达到85%。【结论】‘翠冠’‘苏翠1号’‘鄂梨2号’在梨树“双臂顺行式”棚架栽培管理模式下具有生长优势。

BMP-2/mBGPs/PLGA复合支架对唇腭裂骨缺损修复的体内外研究

为制备具备促进成骨和血管生成能力的人工多孔生物材料支架并探索其性能,本研究采用引入扩孔剂的水热合成法制备了大孔径介孔生物活性玻璃(mBGPs),通过真空浸渍法将骨形态发生蛋白-2(BMP-2)负载到mBGPs介孔中,随后结合溶剂浇铸粒子沥滤法成功制备了BMP-2/mBGPs与PLGA复合支架。材料表征结果表明,mBGPs呈空心球壳形式,为非晶相结构,具有无序的三维泡沫孔道结构,能持续溶出钙离子、磷酸根离子和硅酸根离子,同时mBGPs具有蛋白质负载和缓释的能力。体外实验结果表明,BMP-2/mBGPs/PLGA多孔支架利于大鼠骨髓间充质干细胞(rBMSCs)的黏附与增殖,能显著提高生物活性物质的分泌和表达。大鼠牙槽骨缺损动物模型的修复实验表明,该支架加速了新骨组织的生长速度和成熟。

基于支架和无支架策略在生长板软骨再生治疗中的应用

背景:组织工程是一种理想的生长板再生治疗方式,然而目前大多数的再生组织工程研究都是建立在传统支架策略的基础之上,随着传统支架的局限性逐渐显露,研究的方向也逐渐多样化。目的:总结基于支架和无支架策略在生长板软骨再生治疗中的应用以及各自的优势和不足。方法:检索PubMed、Wiley、Elsevier数据库收录的相关文献,英文检索词为“growth plate injury,regeneration,tissue engineering,scaffold,scaffold-free,biomimetic,cartilage”。检索时限为1990-2023年,最终纳入104篇文献进行综述。结果与结论:仿生支架策略是通过模拟生长板独特的组织结构最大程度上还原每个区域的细胞组成、生物信号和独特力学性能,进而构建能促进组织再生的仿生微环境,因此,仿生支架的设计是尽可能地从成分、结构和力学性能上模拟原生生长板,虽然取得一定的成效,但仍存在再生效果不稳定的问题。无支架策略认为支架的局限性会对再生治疗产生不利影响,因此,无支架构建物的设计是尽可能地依赖于细胞自身产生和维持细胞外基质的能力,不干扰细胞-细胞间的信号,不引入外源性物质,但存在稳定性较差、机械强度低,操作难度较大等问题。仿生策略和无支架策略的出发点不同且均存在各自的优缺点,但它们对于生长板软骨再生均能产生积极的作用。因此,后续的研究不论是采取仿生策略或无支架策略,都将聚焦于对现有技术的不断优化,以期实现有效的生长板软骨再生治疗。

基于炎症微环境调控组织工程再生性牙髓治疗

背景:近年来,再生性牙髓治疗概念随着组织工程的发展逐渐形成,炎症微环境在调控牙髓再生方面起着关键作用。目的:文章从炎症牙髓微环境变化出发,着眼于炎症与再生平衡,重点介绍炎症微环境中组织工程再生性牙髓治疗的研究进展,为未来再生性牙髓治疗的研究提供参考。方法:在PubMed和中国知网数据库中进行检索,中文检索词为“牙髓再生,炎症,再生性牙髓治疗,组织工程”;英文检索词为“pulp regeneration,inflammation,regenerative endodontic therapy,tissue engineering”,分别检索2013-2023年发表的相关文献,最终纳入61篇文献进行综述分析。结果与结论:①牙髓炎症微环境的变化涉及一系列细胞与分子反应,随炎症进展,微环境对组织修复的作用弊大于利。②炎症通过干细胞募集及激活补体系统等方式促进牙髓再生,也能通过免疫抑制、纤维化破坏再生过程。③组织工程三要素(干细胞、生长因子及支架材料)协同介导炎症反应以恢复炎症-再生平衡,如利用白细胞介素6调节牙髓干细胞功能介导炎症微环境以促进牙髓再生。④当前研究缺乏对感染、炎症问题的关注,牙髓炎症微环境的变化机制尚不清晰,通过有机结合组织工程再生性牙髓治疗的三要素调控炎症微环境,构建再生微环境,精准地调控炎症-再生平衡或是提高临床适用性的突破口之一,但该部分研究仍存在较大空缺,期望未来的研究就如何实现炎症环境下的牙髓再生展开更多的探索,也还需更多动物实验、随机临床试验为组织工程再生性牙髓治疗的临床实践奠定基础。

组织工程技术修复颞下颌关节:问题与挑战

背景:颞下颌关节疾病的传统疗法受限于疾病严重程度和个体差异。相比之下,组织工程作为一种新兴治疗方法,可以根据患者具体情况定制个性化治疗方案,减少手术过程中的不确定性,提高治疗效果。目的:综述组织工程修复颞下颌关节的最新研究成果和进展。方法:以“颞下颌关节,组织工程,种子细胞,支架,生长因子,动物模型”为中文检索词,以“temporomandibular joint,tissue engineering,seed cell,scaffold,growth factor,animal model”为英文检索词,分别在PubMed数据库和中国知网进行文献检索,检索时限为各数据库建库时间至2024年3月。通过分析和阅读文献进行筛选,按照排除筛选标准纳入文献,最终纳入57篇文献进行综述。结果与结论:(1)随着生物学、材料学与工程学等技术的发展,颞下颌关节组织工程己取得较大进展,例如种子细胞的筛选、新型支架的开发、生长因子作用机制的探索、多种动物模型的构建等,目前大多数研究尚处于体外实验阶段,动物实验等体内研究尚未大规模开展,组织工程修复颞下颌关节的临床应用还需更多证据支持。(2)尽管颞下颌关节组织工程研究仍存在许多问题和挑战等待解决,依然展现出广阔的临床应用前景,有望在将来成为颞下颌关节疾病出色高效的治疗方式。

三维孔道结构的HA@Ag@ZIF-8@BG可降解支架的制备及性能

采用3D打印技术制备了生物活性玻璃(BG)支架,并通过1150℃烧结得到了纯BG支架。以金属有机框架(ZIF-8)、硝酸银、透明质酸(HA)为原料,采用原位生长和双溶剂的方法成功制备了不同组分的HA@Ag@ZIF-8@BG支架。利用Zeta、BET、XRD、FT-IR和SEM对材料的微观结构和性能进行了研究,探究了各组分支架的孔隙率、抗压强度以及降解能力。结果表明:原位生长未改变BG支架的原有三维孔道结构和孔隙率;支架的抗压强度仍处于人体松质骨力学强度范围;由于ZIF-8、Ag^(+)和HA的加入减缓了支架在14天内的降解,降解率维持在较低的8.5%左右,细胞生存的弱碱性环境未受影响,可促进细胞和新骨组织的生长。

缓释BMP-2透明质酸-肝素支架的制备及其对牙髓干细胞分化的研究

目的:为了使透明质酸(hyaluronic acid,HA)具备负载和释放生长因子的能力,设计制备透明质酸-肝素(hyaluronic acid-heparin,HA-Hep)支架作为骨形态发生蛋白2(bone morphogenetic protein 2,BMP-2)缓释载体,并探讨其对牙髓干细胞(dental pulp stem cells,DPSCs)成牙本质分化的影响。方法:化学方法制备不同投料比HA-Hep材料。通过傅立叶变换红外光谱与元素分析技术表征肝素与HA的接枝位点、效率等特点。扫描电镜观察该材料微观形态和结构特点。借助静电吸附法将BMP-2加载至HA-Hep,并测绘其释放曲线。通过测定DPSCs增殖情况评价该材料的生物相容性。qPCR检测成牙分化相关基因的表达水平,评估HA-Hep负载BMP-2对DPSCs成牙分化的影响。结果:HA-Hep微观呈疏松多孔网状结构,能够缓释BMP-2达28 d,且释放速率随材料肝素含量比例的增加呈减缓趋势。HA-Hep对DPSCs增殖有促进作用,且与材料浓度呈正相关;qPCR结果表明,与对照组相比,载BMP-2的HA-Hep材料组牙本质涎磷蛋白(dentin sialophosphoprotein,DSPP)、Ⅰ型胶原蛋白(typeⅠcollagen,Col-1)和牙本质基质蛋白-1(dentin matrix protein-1,DMP-1)表达水平在7、14 d均显著升高(均P<0.001)。结论:肝素修饰HA能延缓BMP-2释放,HA-Hep负载BMP-2可上调DPSCs成牙基因(DSPP、Col-1、DMP-1)的表达,有助于生长因子在细胞分化中发挥长期效应。

Application of Decellularized Scaffold Combined with Loaded Nanoparticles for Heart Valve Tissue Engineering in vitro

The purpose of this study was to fabricate decelluarized valve scaffold modified with polyethylene glycol nanoparticles loaded with transforming growth factor-β1（TGF-β1）,by which to improve the extracellular matrix microenvironment for heart valve tissue engineering in vitro.Polyethylene glycol nanoparticles were obtained by an emulsion-crosslinking method,and their morphology was observed under a scanning electron microscope.Decelluarized valve scaffolds,prepared by using trypsinase and TritonX-100,were modified with nanoparticles by carbodiimide,and then TGF-β1 was loaded into them by adsorption.The TGF-β1 delivery of the fabricated scaffold was measured by asing enzyme-linked immunosorbent assay.Whether unseeded or reseeded with myofibroblast from rats,the morphologic,biochemical and biomechanical characteristics of hybrid scaffolds were tested and compared with decelluarized scaffolds under the same conditions.The enzyme-linked immunosorbent assay revealed a typical delivery of nanoparticles.The morphologic observations and biological data analysis indicated that fabricated scaffolds possessed advantageous biocompatibility and biomechanical property beyond decelluarized scaffolds.Altogether this study proved that it was feasible to fabricate the hybrid scaffold and effective to improve extracellular matrix microenvironment,which is beneficial for an application in heart valve tissue engineering.

A bifunctional bone scaffold combines osteogenesis and antibacterial activity via in situ grown hydroxyapatite and silver nanoparticles

Hydroxyapatite(HA)nanoparticles and silver(Ag)nanoparticles are expected to enable desirable bioactivity and antibac-terial properties on biopolymer scaffolds.Nevertheless,interfacial adhesion between HA/Ag and the biopolymer is poor due to the large physicochemical differences between these components.In this study,poly L-lactic acid(PLLA)powder was first surface-modified with bioactive polydopamine(PDA)in an alkaline environment.Next,HA and Ag nanoparticles were grown in situ on the PDA-coated PLLA powder,which was then adhered to the porous bone scaffold using a selective laser-sintering process.Results showed that HA and Ag nanoparticles were homogenously distributed in the matrix,with enhanced mechanical properties.Simulated body fluid bioactivity tests showed that the in situ grown HA-endowed scaffold shows excellent bioactivity.In vitro tests confirmed that the scaffold exhibits favorable biocompatibility with human umbilical cord mesenchymal stem cells,as well as strong antibacterial activity against Gram-negative Escherichia coli.Furthermore,in vivo assays indicated that the scaffold promoted bone generation,with a new bone area fraction of 71.8%after 8 weeks’implantation,without inflammation.

Chondrogenesis of Precartilaginous Stem Cells in KLD-12 Self-assembling Peptide Nanofiber Scaffold Loading TGF-β3 Gene

The effect of culture in KLD-12 self-assembling peptide nanofiber scaffold containing TGF-β3 gene on differentiation of precartilaginous stem cells （PSCs） into chondrocytes was studied. KLD-12 was synthesized by solid-state method. After TGF-β3 plasmid was loaded into KLD-12 self-assembling peptide nanofiber scaffold, DNA release ability was investigated. PSCs and hTGF-β3 gene were loaded into KLD-12 3-D scaffold, and MTT assay was performed to investigate the cell proliferation, and ELASA assay was used to investigate the expression of TGF-β3. Specific cartilage matrix was examined by quantitative real-time PCR, immunohistochemistry and Alcian Blue staining. Compared with control group, DNA synthesis level of PSCs reached the peak within 3 days when PSCs were cultured in self-assembling peptide nanofiber scaffold loading TGF-β3 plasmid, and maintained this high level within 2 weeks. MTT results showed that the proliferation ability of experimental group was statistically higher than that in control group （P〈0.05）. Quantitative real-time PCR suggested that the percentage of TGF-β3 positive PSCs in experimental group was higher than that in control group （P〈0.01）. ELISA assay showed that the TGF-β3 protein level increased in supernatant of experimental group＇s PSCs, reached the peak after 72 h and then declined a little to the plateau phase. Compared with the control group, the specific gene of chondrocyte typical extracellular matrix significantly up-regulated （P〈0.01）. The results showed that PSCs differentiated into chondrocytes in self-assembling peptide nanofiber scaffold loading TGF-β3 plasmid, which provided a fresh approach to cartilage tissue engineering.

Smart scaffolds in bone tissue engineering: A systematic review of literature

AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.

Coaxial electrohydrodynamic printing of core–shell microfibrous scaffolds with layer-specific growth factors release for enthesis regeneration

The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.

Research Progress of Osteochondral Composite Scaffolds in Tissue Engineering Cartilage Repair

Repair and regeneration of articular cartilage has always been a major challenge in the medical field due to its peculiar structure(e.g.sparsely distributed chondrocytes,no blood supply).Cartilage tissue engineering is one promising strategy for cartilage repair,however,one critical issue for cartilage tissue engineering is the integration between tissue-engineered and native cartilage.In recent years,osteochondral tissue engineering has attracted growing interest for overcoming this problem.Herein,we review the development of osteochondral tissue engineering.Firstly,currently used seed cells in osteochondral tissue engineering will be described.Secondly,several types of scaffolds and their(dis)advantage for osteochondral tissue engineering will be introduced.Thirdly,the growth factors currently used in osteochondral tissue engineering will be presented and discussed.

富血小板血浆及浓缩生长因子和微纳米3D复合支架修复兔桡骨缺损的比较

背景:近年来,富血小板血浆、浓缩生长因子和3D打印的纳米级羟基磷灰石支架成为骨移植的热门研究材料,目前这些材料的研究方向较分散,现有研究中鲜有针对大段骨缺损的治疗且缺乏不同类型材料的比较,因长骨干的主要成分为皮质骨,其愈合更具挑战。目的:通过实验评估和比较富血小板血浆、浓缩生长因子和微纳米3D复合支架对骨缺损愈合的影响。方法:纳入32只新西兰大白兔,制备桡骨15 mm骨缺损模型,根据不同移植物随机分为4组:空白组(不做处理)、富血小板血浆组(富血小板血浆)、浓缩生长因子组(浓缩生长因子)和3D复合支架组(微纳米3D复合支架),每组8只。术后第1天及第6,12周行X射线检查,在术后12周先行行为学观察,之后取兔尺桡骨标本行Micro CT扫描,对比骨密度和骨体积分数,最后将骨标本切片后显微镜下观察。结果与结论:①富血小板血浆组、浓缩生长因子组和3D复合支架组均有不同程度的新骨形成,行为学观察差异较小;而空白组基本无新骨形成,术后12周均出现明显的跛行;②在术后6,12周的X射线成像上各干预组要优于空白组,而各干预组之间对比灰度值差异也较明显,但富血小板血浆组和浓缩生长因子组在12周未见明显差异;③术后12周富血小板血浆组和浓缩生长因子组在骨密度和骨量对比上无显著差异,但各参数均优于3D复合支架组;④提示富血小板血浆和浓缩生长因子无疑能促进早期新骨形成,且两者在长远影响中无明显差异;由羟基磷灰石制作的无机材料支架难以完全促进骨缺损愈合,需加入其他有机成分改善其性能才能发挥最大的成骨效能。

聚乳酸-羟基乙酸共聚物微球在骨组织工程中的应用

背景:聚乳酸-羟基乙酸共聚物微球具有良好的生物相容性、生物安全性和生物降解性,作为载体已经被广泛应用于骨组织工程中,但其仍有缺乏亲水性、副产物酸性及缺乏功能化等缺点,因此需要进行不同的修饰改性方能更好地应用。目的:对聚乳酸-羟基乙酸共聚物微球在骨组织工程中的应用进行综述。方法:以“poly(lactic-co-glycolic acid)copolymer microsphere,PLGA microsphere,growth factor,drug deliver,modified,functional modification,composite scaffold,bone tissue engineering”为检索词在Web of Science和PubMed数据库检索自2000年1月至2022年6月收录的相关文献,并将其进行筛选和分析,最终选择83篇文献进行综述。结果与结论:①聚乳酸-羟基乙酸共聚物微球的理化性质与其乳酸和羟基乙酸比、分子质量和端基团等因素有关。目前,乳酸和羟基乙酸比例为75∶25、相对分子质量为75000-100000,端羧基的聚乳酸-羟基乙酸共聚物在制备微球时应用较多。②现在常用的制备方法主要包括乳化法、微流控技术、电喷雾、喷雾干燥和超临界流体法。具体的制备方法需结合微球的应用需求及生产条件来选择,随着技术的成熟与进步,未来会有更稳定、高效的生产方式。③聚乳酸-羟基乙酸共聚物微球的修饰改性包括负载生长因子和药物、功能化修饰以及以微球为基础构建复合支架。负载生长因子可促进细胞分化、血管生成,从而促进骨组织的修复与再生;负载药物可治疗多种骨骼类疾病;复合无机矿物可以提高聚乳酸-羟基乙酸共聚物的力学性能,而且提供骨组织生长所需的微量元素,更多的被用于骨缺损的治疗;通过增加微球调控细胞的分泌与活性的能力,参与疾病的免疫调控,为疾病治疗提供新思路;以聚乳酸-羟基乙酸共聚物微球为基础的复合支架,在支架原有的优点外,还能增加微创递送药物、缓释药物的能力,但是距离临床应用还需进一步研究证实。④聚乳酸-羟基乙酸共聚物微球在未来有望根据骨组织工程的不同需求,制定不同的修饰方法,从而生产出针对不同疾病具有特定功能的微球。