Pores Created by Laser Surface Modification of Poly(vinylalcohol)-Collagen with Glycosaminoglycan Scaffold for Cell Culture in Tissue Engineering

A PVA- GAG- COL composite scaffold is fabricated by polyvinyl alcohol (PVA), glycosaminoglycan (GAG) and collagen (COL). Laser surface modification technology is used to make holes on the surface of the scaffolds. Inside and outside interconnection microporous structure is obtained. Biocompatibility test of the scaffolds shows that PVA- GAG- COL scaffold can promote the adhesion and proliferation of the fibroblast. Also, fibroblast can grow normally on the scaffolds with pore diameter from 115 um to 255 um and pore distance from 500 um to 2000 um. PVA- GAG- COL scaffolds possess excellent cell biocompatibility. The porous structure is suitable for cell culture in tissue engineering.

Surface modification of small intestine submucosa in tissue engineering

With the development of tissue engineering,the required biomaterials need to have the ability to promote cell adhesion and proliferation in vitro and in vivo.Especially,surface modification of the scaffold material has a great influence on biocompatibility and functionality of materials.The small intestine submucosa(SIS)is an extracellular matrix isolated from the submucosal layer of porcine jejunum,which has good tissue mechanical properties and regenerative activity,and is suitable for cell adhesion,proliferation and differentiation.In recent years,SIS is widely used in different areas of tissue reconstruction,such as blood vessels,bone,cartilage,bladder and ureter,etc.This paper discusses the main methods for surface modification of SIS to improve and optimize the performance of SIS bioscaffolds,including functional group bonding,protein adsorption,mineral coating,topography and formatting modification and drug combination.In addition,the reasonable combination of these methods also offers great improvement on SIS surface modification.This article makes a shallow review of the surface modification of SIS and its application in tissue engineering.

Engineering multifunctional bioactive citrate-based biomaterials for tissue engineering

Developing bioactive biomaterials with highly controlled functions is crucial to enhancing their applications in regenerative medicine.Citrate-based polymers are the few bioactive polymer biomaterials used in biomedicine because of their facile synthesis,controllable structure,biocompatibility,biomimetic viscoelastic mechanical behavior,and functional groups available for modification.In recent years,various multifunctional designs and biomedical applications,including cardiovascular,orthopedic,muscle tissue,skin tissue,nerve and spinal cord,bioimaging,and drug or gene delivery based on citrate-based polymers,have been extensively studied,and many of them have good clinical application potential.In this review,we summarize recent progress in the multifunctional design and biomedical applications of citrate-based polymers.We also discuss the further development of multifunctional citrate-based polymers with tailored properties to meet the requirements of various biomedical applications.

Evaluation of Novel 3D Architectures Based on Knitting Technologies for Engineering Biological Tissues

Textile-based technologies are considered as potential routes for the production of 3D porous architectures for tissue engineering( TE) applications. We describe the use of two polymers,namely polybutylene succinate( PBS) and silk fibroin(SF) to produce fiber-based finely tuned porous architectures by weft and warp knittings. The obtained knitted constructs are described in terms of their morphology, mechanical properties,swelling ability,degradation behaviour,and cytotoxicity. Each type of polymer fibers allows for the processing of a very reproducible intra-architectural scaffold geometry,with distinct characteristics in terms of the surface physicochemistry,mechanical performance,and degradation capability,which has an impact on the resulting cell behaviour at the surface of the respective biotextiles. Preliminary cytotoxicity screening shows that both materials can support cell adhesion and proliferation. Furthermore, different surface modifications were performed( acid /alkaline treatment, UV radiation,and plasma) for modulating cell behavior. An increase of cell-material interactions were observed,indicating the important role of materials surface in the first hours of culturing. Human adipose-derived stem cells( hASCs) became an emerging possibility for regenerative medicine and tissue replacement therapies. The potential of the recently developed silk-based biotextile structures to promote hASCs adhesion,proliferation,and differentiation is also evaluated. The obtained results validate the developed constructs as viable matrices for TE applications. Given the processing efficacy and versatility of the knitting technology, and the interesting structural and surface properties of the proposed polymer fibers,it is foreseen that our developed systems can be attractive for the functional engineering of tissues such as bone,skin,ligaments or cartilage and also for develop more complex systems for further industrialization of TE products.

基于非基因工程技术的细胞表面修饰策略研究进展

细胞表面成分与结构在维持细胞内代谢环境稳定、控制细胞内外物质交换和促进细胞间通讯方面发挥着至关重要的作用,因此,调节或改变细胞表面成分对研究细胞命运具有重要意义。基因工程是目前调节细胞表面成分最常用的技术,但是由于这种方法具有转染效率低、存在突变风险等问题,其应用范围仍然有限。相比之下,近些年发展起来的多种非基因工程细胞表面修饰技术,具有简便、易操作、适用范围广等优势,为调控细胞生命活动、赋予细胞新的性质和功能提供了更多新的选择,因而其在基础生物学研究和新药研发中具有广泛应用前景。对目前非基因工程技术的原理、特点以及在细胞治疗领域的应用等进行了综述和讨论,期望有助于深入了解这一新技术及其在生物医学领域中的应用。

Magnesium-based alloys with adapted interfaces for bone implants and tissue engineering

Magnesium and its alloys are one of the most used materials for bone implants and tissue engineering.They are characterized by numerous advantages such as biodegradability,high biocompatibility and mechanical properties with values close to the human bone.Unfortunately,the implant surface must be adequately tuned,or Mg-based alloys must be alloyed with other chemical elements due to their increased corrosion effect in physiological media.This article reviews the clinical challenges related to bone repair and regeneration,classifying bone defects and presenting some of the most used and modern therapies for bone injuries,such as Ilizarov or Masquelet techniques or stem cell treatments.The implant interface challenges are related to new bone formation and fracture healing,implant degradation and hydrogen release.A detailed analysis of mechanical properties during implant degradation is extensively described based on different literature studies that included in vitro and in vivo tests correlated with material properties’characterization.Mg-based trauma implants such as plates and screws,intramedullary nails,Herbert screws,spine cages,rings for joint treatment and regenerative scaffolds are presented,taking into consideration their manufacturing technology,the implant geometrical dimensions and shape,the type of in vivo or in vitro studies and fracture localization.Modern technologies that modify or adapt the Mg-based implant interfaces are described by presenting the main surface microstructural modifications,physical deposition and chemical conversion coatings.The last part of the article provides some recommendations from a translational perspective,identifies the challenges associated with Mg-based implants and presents some future opportunities.This review outlines the available literature on trauma and regenerative bone implants and describes the main techniques used to control the alloy corrosion rate and the cellular environment of the implant.

组织工程治疗股骨头坏死软骨下分离的适用技术

背景:股骨头坏死出现新月征是病情进程的“分水岭”,修复和稳定骨-软骨界面对阻止病情继续进展和预防股骨头塌陷尤为重要。利用组织工程学同步修复、整合骨-软骨界面具有潜在优势。目的:综述探讨解决股骨头坏死软骨下分离的潜在适宜技术。方法:检索1970年1月至2023年4月PubMed、Web of Science及中国知网、万方数据库中发表的相关文献,英文检索词:“Femoral head necrosis,Avascular necrosis of femoral head,Osteonecrosis of femoral head”等,中文检索词:“股骨头坏死,软骨下骨,软骨,软骨与软骨下骨整合”等,最终纳入114篇文献进行综述分析。结果与结论:①结构缺陷、缺血缺氧环境、炎症因素和应力集中可能造成股骨头坏死软骨下分离现象,软骨下骨分离会造成塌陷进展,并且可能与保髋手术失败相关,利用组织工程支架实现支架与骨-软骨界面的整合是治疗股骨头坏死软骨下分离的潜在方法之一。②目前的文献研究表明,多相、梯度支架和复合材料在促进骨、软骨细胞黏附与增殖,骨软骨基质的沉积方面均有提升,有助于支架与骨-软骨界面的整合,对治疗股骨头坏死软骨下分离有参考价值。③通过对支架表面进行修饰可以提高与界面整合的效率,但有各自不同的优缺点,提供不同环境的支架能够诱导同种间充质干细胞差异分化,有助于不同界面之间的整合。④未来有望应用于股骨头坏死软骨下分离的支架应为复合材料,具有梯度化和差异化的仿生结构,通过表面修饰和干细胞加载促进骨-软骨界面与支架的整合以实现治疗目的,但仍需进一步研究验证,而支架的降解速率与修复进度同步和不同界面之间的稳定性是未来需要解决的主要问题。

3D打印多孔钽内部结构及表面改性在骨组织工程学中的研究进展

3D打印多孔钽在骨缺损的修复方面具有独特优势,其具有良好的物理、化学、机械性能及生物相容性等优点,展现了其在人类骨组织工程学领域中巨大的临床价值,具有广阔的应用前景,但仍需在多孔钽的内部结构及表面修饰方面有新的突破。现通过回顾及分析相关文献,对3D打印多孔钽的内部结构及表面改性在骨组织工程中的研究进展作一综述。

骨组织工程中促血管支架应用的可视化分析

背景:对于支架物理性质的研究始终是组织工程研究领域的热点,但对于促血管支架来说,除了要满足支架的基本性能外,还需要通过其他方法来促进血管在支架内的再生过程,以达到修复骨组织的最终目的。目的:对国内外发表的骨组织工程下促血管支架的文献进行可视化分析,探究该领域的研究热点及研究现状,为后续研究提供参考。方法:以中国知网及Web of Science核心集数据库为检索库,检索骨组织工程下促血管支架的相关文献,去除不符合纳入标准的文献,随后导入CiteSpace 6.1.R2软件,对研究领域的作者、国家机构及关键词进行可视化分析。结果与结论:①骨组织工程下促血管支架应用的研究中,发文量最多的前3个国家分别为中国、美国和德国。②中国知网数据库机构该领域研究发文量排名前3位分别为南方医科大学、华中科技大学、东华大学;Web of Science核心集数据库中机构发文量排名前3位分别为上海交通大学、四川大学、中国科学院。③中国知网数据库关键词频次排名前3位为“组织工程、血管化、血管生成”,Web of Science核心集数据库关键词频次排名前3位为“mesenchymal stem cell(间充质干细胞),scaffold(支架),vascularization(血管化)”。④参考文献共被引情况和高被引文献分析显示,该领域的血管化策略研究热点为支架设计、血管生成因子的输送、体外共培养和体内预血管化;技术方面研究热点为3D打印、静电纺丝、血管移植及血管融合;机制方面研究热点为免疫调节和巨噬细胞、药物/生长因子输送、内皮细胞和成骨细胞之间的关系、骨细胞和内皮细胞之间旁分泌关系及信号分子通路、血管生成和抗血管生成分子。⑤国内外骨组织工程下促血管支架应用研究均十分重视干细胞和3D打印技术的运用,而目前的研究热点主要为生物3D打印技术、支架改性修饰的方法以及基于骨修复机制智能生物材料的开发应用。

改性HA纳米粒子在骨组织工程中的研究进展

随着中国老龄化社会进程加快,以及疾病和交通事故等因素的影响,骨损伤病例呈逐年增加趋势,使骨替代材料的市场需求不断扩大。羟基磷灰石(HA)具有优异的生物活性和生物相容性,是人类和动物骨骼的主要组成成分,在生物体内可降解、参与代谢,释放出的离子对机体无害,被广泛应用于骨修复、再生和置换等骨组织工程,但HA纳米粒子分散性差、强度低、高分子相容性差等缺点,限制了其应用。为了克服这些缺点,探索改性或复合HA的方法,以改善其分散性、亲水性、抗菌性及机械强度等,来满足临床应用的要求。该文重点总结了当前主流的HA纳米粒子的改性方法,包括离子掺杂、表面改性、材料复合。详细介绍了目前HA复合材料的研究热点,以期为HA复合材料相关基础研究提供有益的借鉴与启示。

金属离子掺杂羟基磷灰石骨修复材料的特性及应用

背景:目前用于骨修复的自体骨和异体骨存在来源有限、供骨区并发症、潜在的疾病传播风险、免疫排斥反应及价格昂贵等问题,临床应用受到限制,人工骨修复材料作为骨移植替代材料得到了广泛研究。目的:总结金属离子掺杂改性羟基磷灰石用于骨组织修复的研究现状。方法:检索2000年1月至2022年5月PubMed、Web of Science、中国知网及万方数据库收录的相关文献,中文检索词为“金属离子、羟基磷灰石、掺杂改性、骨修复”,英文检索词为“Metal ion,Hydroxyapatite,Doping modification,Bone repair”。最终纳入61篇文献进行综述分析。结果与结论:①离子掺杂羟基磷灰石具有良好的特性,锶可增强成骨细胞的骨生成过程,并抑制破骨细胞介导的骨吸收,锶掺杂羟基磷灰石在骨质疏松性骨缺损修复方面具有独特的优势。②铜、锌、银、镁、铁具有一定的抗菌活性,其中银、锌具有优异的抗菌性,掺杂改性羟基磷灰石对预防和治疗骨科感染具有重要意义。③铜可促进血管内皮细胞迁移,增加血管生成,掺铜羟基磷灰石可用于乏血管部位的骨组织修复。钡具有显影性,与羟基磷灰石等其他材料复合可制备显影骨修复材料。④锶-铁共掺杂羟基磷灰石可调节细胞免疫,促进血管和骨生成。镁、锌-锶掺杂的羟基磷灰石可诱导利于成骨的弱碱性环境,具有优异的成骨能力。⑤一定含量的镁掺杂的羟基磷灰石具有与皮质骨相匹配的抗压强度,有望用于负重部位的骨组织修复。低浓度的离子掺杂可提高羟基磷灰石的机械性能和成骨活性,并赋予其抗菌活性、促血管生成、免疫调节等能力。⑥当离子浓度过高时,则会产生毒性作用,目前关于各离子的最佳掺杂浓度尚无定论,未来需深入研究。⑦离子参与骨代谢的机制以及是否会影响其他细胞活动需关注探索;如何实现植入材料的缓慢降解、金属离子的缓慢释放,使其与骨修复过程相匹配,有待进一步研究。⑧优化羟基磷灰石的合成方法和离子掺杂技术,制备与天然骨机械性能匹配的材料是今后研究的一个方向。

小口径人工血管的早期血栓形成与预防

背景:小口径人工血管在外周血管疾病治疗中有着广泛的应用价值,但因早期血栓形成导致移植失败的问题亟待解决。目的:总结小口径人工血管早期血栓形成与预防的研究进展。方法:由第一作者检索中国知网、万方、PubMed和Google Scholar数据库2000-2020年发表的相关文献,中文检索词为“小口径人工血管,小口径管状支架,组织工程血管,抗血栓,血栓形成,血液相容性,亲水性,内皮化”,英文检索关键词为“small-caliber vascular graft,vascular tissue engineering applications,endothelialization,hemocompatibility,surface modification”,检索国内外有关小口径人工血管血栓形成的病理生理机制及预防血栓形成的相关文献,就生物材料的表面改性和内皮化研究作为纳入标准,最终选取57篇文献进行综述。结果与结论:预防血栓形成是小口径人工血管研究的热点与难点,从近几年的国内外研究进展来看小口径人工血管早期血栓形成与血浆蛋白吸附、凝血因子的接触激活有关,通过提高表面亲水性、释放抗血栓物质、种植种子细胞、靶向基因诱导等方法,小口径人工血管血栓形成的状况得到一定程度改善,但当前仍处于试验阶段,距离临床应用尚有一定距离,仍需进一步探索或优化一种更适宜的血管材料,为临床应用提供更多选择。

Polydopamine-modified chitin conduits with sustained release of bioactive peptides enhance peripheral nerve regeneration in rats

The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration.However,neurotrophic facto rs are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose,which limits their clinical benefits.Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth fa ctors and can activate the equivalent receptors but have simplified sequences and structures.In this study,we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth fa ctor mimetic peptides(Chi/PDA-Ps).We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides.In this study,we evaluated the biocompatibility of the Chi/P DA-Ps conduits.Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth fa ctor mimetic peptide synergistically promoted prolife ration of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro.The Chi/P DA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury.We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy.The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and re myelination was further resto red.These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.

A Brief Review on Hydroxyapatite Nanoparticles Interactions with Biological Constituents

With the pursuit of new cancer therapies and more effective treatment to diseases in the last decades, nanotechnology has been an important ally for healthcare professionals and patients in critical clinical conditions. Nanomaterials offer an alternative way to deliver toxic chemotherapeutic drugs to specific biological tissues, specific cells or specific microbial beings, resulting in avoidance of strong side effects or resilience to effective drugs. Among these materials, stands out the hydroxyapatite nanoparticles, a ceramic class of calcium phosphates that present chemical and structural similarities with the mineral phase of the human skeleton’s bone matrix, resulting in important biological features, such as biocompatibility, osteoconductive, osteoinduction and osteoaffinity, which led to a lot of scientific researches to apply these nanoparticles for bone diseases diagnosis and therapeutics. Due to the hydroxyapatite biological activities and due to the possibility to promote chemical and physical modifications in these nanoparticles, they can interact with biological cells or microorganisms in different ways, resulting in multiple potentialities to be explored such as apoptosis induction to cancerous cells, osteogenesis promotion, cellular proliferation, angiogenesis and tissue recovery, in addition to promote cell adhesion and cell uptake. Furthermore, chemical and physical modifications, such as surface functionalization, dopant inclusions and radiolabeling process, allow scientists to track the particle activities in biological environments. In the last decades of scientific productions, the literature brings together important data on how hydroxyapatite nanoparticles interact with biological tissues and such data are crucial for the development of more effective therapeutic and diagnostic agents. In the present review, we intend to compile scholarly information to explore the biological relations of nanosized hydroxyapatite with the human cellular environment and the feasible modifications that may improve the theragnostic efficacy of these molecules.

组织工程相关壳聚糖-明胶基生物材料

壳聚糖的N 乙酰基葡萄糖胺组成成分为糖胺聚的结构特征 ,而明胶则为胶原的部分变性衍生物 ,由其开发的生物材料呈现和前体相当的生物活性。本文综述了壳聚糖 明胶基生物材料的最近进展 ,包括用壳聚糖 明胶网络基生物材料制备膜材料、支架 ,且作为表面修饰剂用于组织工程。N 烷基化壳聚糖用作DNA释放的非病毒载体。这些生物材料在皮肤、软骨、骨组织工程和基因治疗方面呈现良好的应用前景。

RGD多肽修饰的改性PLGA仿生支架材料对骨髓间充质干细胞粘附、增殖及分化影响的研究

目的:探索RGD多肽修饰的改性PLGA支架材料上骨髓基质细胞的增殖、粘附及分化情况。方法用异型双功能交联剂Sulfo-LC-SPDP将GRGDSPC多肽共价结合到改性PLGA支架材料上,以未接多肽的改性PLGA材料做对照,取第三代MSC接种到材料上,培养1d、2d、3d、4d后比较材料上的细胞密度来反映细胞的增殖程度;取第三代MSC接种到材料上,培养4h、12h后沉淀法定量检测粘附的细胞数,培养24h后摄光镜图像比较粘附细胞的数量和形态,并用FITC连接的鬼笔环肽对细胞骨架染色,在荧光显微镜下观察细胞骨架的组织情况;取第三代MSC接种到材料上,用成骨性培养基培养7d、14d、21d,检测细胞中ALP活性来了解MSC分化情况。结果:培养1d、2d、3d、4d后细胞的增殖程度无显著性差异;培养4h、12h后实验组细胞粘附率均显著高于对照组,且24h后细胞的粘附质量、细胞骨架的组织情况也较对照组为好;培养14d后实验组细胞表达显著高的ALP活性。结论:RGD多肽修饰对细胞增殖无明显促进作用,但能提高改性PLGA支架材料对骨髓基质细胞的粘附性,对MSC向成骨细胞分化有显著促进作用。

低温等离子体技术在生物材料表面改性中的应用

综述了低温等离子体技术在生物材料表面改性中的应用。概述了低温等离子体分类、特征及其与生物材料表面作用的机理;介绍了低温等离子体聚合、低温等离子体处理、低温等离子体接枝聚合对生物材料表面改性的原理以及它们在生物材料领域中的最新应用进展和应用前景。

组织工程生物支架材料

组织工程支架材料表面的微观和亚微观结构对细胞的黏附与生长有很重要的影响 ,纳米结构材料的应用为该结构展现了较广阔的前景。另外 ,组织工程支架材料的表面修饰及孔径调控对生物材料的改进有很重要的作用。介绍了生物材料的基本要求和分类 ,纳米结构材料在组织工程中的应用及生物材料表面修饰 ,以及以泡沫支架为例介绍材料孔径调控。

改进高分子材料细胞亲和性的研究——聚(D,L-乳酸)的等离子体处理改性

目的 研究氨等离子体处理对聚 (D,L -乳酸 ) (PDL L A )膜表面改性的效果。方法 用无水氨在不同条件 (射频放电功率、放电时间和反应室气体压力 )下对聚 (D,L -乳酸 )膜进行等离子体处理 ,放电后再抽真空10分钟 ,依次关闭氨的进入并充入大气 ,得到不同表面改性程度的 10组 PDL L A改性膜。分别测定改性膜和未经离子体处理对照膜的表面接触角 ,计算表面自由能 ,并将试膜用于鼠 3T3成纤维细胞的培养。结果 通过等离子体处理的改性膜亲水性得到改善 ,表面自由能得到提高。对鼠 3T3成纤维细胞的培养结果表明 ,用氨等离子体处理的聚 (D,L -乳酸 )改性膜能有效地促进 3T3细胞在膜表面的粘附与生长 ;经过 4天的细胞培养实验表明 ,改性膜上细胞的数量几乎是对照膜的两倍。

组织工程用生物材料的表面修饰技术

介绍了生物材料表面修饰的意义 ,分析总结了表面修饰的技术方法 ;对辐射接枝法、表面固定化、低温等离子体法、离子注入法等几种新的修饰方法进行了评述 ,并对各种修饰方法的优缺点进行了分析比较 ;