光交联水凝胶在组织工程中的研究进展

由于生物相容性、可降解性、与天然细胞外基质结构的相似性,水凝胶成为组织工程的研究热点与重点。基于原位形成和可注射性、与现有加工技术(3D打印、静电纺丝)的兼容性,光交联水凝胶在组织工程领域广泛应用。综述了近年来光交联水凝胶在组织工程领域的研究进展,包括其在软骨组织、骨组织、脂肪组织、牙周组织和皮肤组织方面的研究思路及应用进展,以期为后续光交联水凝胶作为组织工程支架的研究提供参考。     

生物水凝胶及其复合材料在骨修复中的应用

由于外伤、疾病或骨吸收引起的大面积骨缺损无法自行修复,往往需要植入人工骨来恢复缺损区的骨形态和功能。由于传统的异体和异种骨存在易被宿主吸收、排斥等问题,且自体骨取材有限,因此,骨组织工程是目前最具前景和可行的骨修复策略。骨组织工程的关键是要有种子细胞、支架材料以及生长因子,生物水凝胶是潜在的组织工程细胞支架材料之一。水凝胶具有良好的生物相容性和可降解性,越来越受到组织工程领域学者的关注。本文对生物水凝胶在骨组织工程中的应用进行了评述。     

仿生黏弹性高分子水凝胶及其生物医学应用

天然细胞外基质和生物体软组织固有的黏弹性是调控细胞行为和组织修复与再生过程的关键因素.基于动态建构化学反应交联得到的动态高分子水凝胶材料可有效模拟在体细胞或组织的黏弹性力学微环境,为体外调控细胞命运、揭示其力学生物学响应机制提供了重要工具,也为组织修复与再生提供了仿生支架材料.本综述在介绍天然细胞外基质及生物体软组织黏弹性的基础上,重点对仿生黏弹性水凝胶材料的设计思路、性能表征及影响因素等进行了概括和总结,并揭示了黏弹性水凝胶调控细胞、组织行为的规律及机制,最后,分析了目前该领域研究中所存在的问题并对未来发展方向进行了展望.本综述将有助于启发高分子水凝胶的仿生功能化设计思路及材料生物学效应研究,进一步拓展高分子水凝胶材料的生物医学应用.     

促细胞黏附生长的自组装肽水凝胶

随着细胞与组织工程的迅猛发展,能够促进细胞黏附、生长和分化的生物材料基质支架的研究日益重要。具有生物相容性且含水量超过99％的自组装肽水凝胶因其很好地符合理想的生物材料基质支架标准而备受重视。这类自我互补的两亲寡肽含50％的带电残基,并且以交替的离子亲水性和不带电的氨基酸残基周期性重复为特征;在其寡肽的氨基末端可用直接固相合成法修饰几个短序列生物活性模体进行功能化,用以促进不同细胞的黏附生长和靶向定位。现对自组装肽水凝胶的结构特征、自组装机制、对细胞黏附生长的影响以及未来自组装肽生物材料设计的目标进行综述．     

成纤维细胞在壳聚糖/PHEA水凝胶膜上的粘附与生长行为

水凝胶是一类广泛溶涨于水 ,呈三维网状结构的聚合物具有很高的生物相容性 ,广泛地用于生物材料 ,如眼球的晶状体、人造脏器以及人造皮肤等。高含水量的水凝胶不利于细胞粘附 ,研究能使细胞粘附并生长的水凝胶是开发其在组织工程材料领域应用的关键 ,细胞易于粘附的水凝胶可用于细胞培养基材和组织工程移植支架材料。一般来说 ,由于细胞表面带有负电荷 ,带正电荷的基材表面 (如 ,多熔素 (Ｐｏｌｙｌ ｙｓｉｎｅ) )有利于细胞粘附 ,而带有酸性或中性基团的材料不利于细胞粘附[1 ] ,而且带高负电荷密度的基材会导致细胞新陈代谢的紊乱并抑制细…     

骨组织工程天然衍生细胞外基质材料

细胞外基质材料的开发是骨组织工程的重要组成部分,目前,在骨组织工程中应用较多的基质材料可分为天然衍生材料、人工合成材料以及这两种材料的复合材料。介绍了各种天然衍生骨材料如煅烧骨、脱钙骨基质、脱蛋白骨基质、重组合异种骨基质和天然高分子材料如胶原、纤维蛋白、几丁质、藻酸盐及其衍生物以及珊瑚衍生骨在骨组织工程中的应用,展望了骨组织工程细胞外基质材料的未来发展方向,认为未来的理想基质材料应该是集各种材料的优点于一身,能够充分适应体内各种生理环境并能采用智能化的加工方式进行大批量生产的生物仿生材料。     

壳聚糖复合材料在骨组织工程中的应用

支架材料作为骨组织工程的关键三要素之一具有重要的作用。壳聚糖是唯一带正电的天然碱性多糖,其具有良好的生物相容性、生物可降解性、固有的抗菌性以及促进成骨细胞增殖、促成骨分化等优点,在骨组织工程中被广泛用来制备骨组织工程支架材料。但单纯壳聚糖制备的支架材料机械性能较差、生物响应性较低。因此,近些年来基于壳聚糖的复合支架备受人们关注。目前,人们已经研发出了不同类型的壳聚糖基复合材料,包含与无机相、有机相以及多相复合的支架材料等,并对其生物学性能进行广泛研究,主要包括支架材料在细胞体外培养中的作用、支架材料体内修复不同骨缺损的效果和模式等方面。本文对此进行综述,并对今后的研究趋势进行了初步的探讨     

DNA水凝胶的制备及应用

脱氧核糖核酸(Deoxyribonucleic acid,DNA)不仅可作为生物遗传的物质基础,又以其可编程性、功能多样性、生物相容性和生物可降解性等优点,在生物材料的构建方面表现出巨大的潜力。DNA水凝胶是一种主要由DNA参与形成的三维网状聚合物材料,同时因其保留的DNA生物性能与自身骨架的机械性能的完美融合使得它成为近年来最受关注的新兴功能高分子材料之一。目前,基于各种功能核酸序列或通过结合不同的功能材料制备的单组分或多组分DNA水凝胶,已广泛用于生物医学、分子检测及环境保护的研究或应用领域中。文中主要总结了近十几年来DNA水凝胶制备方法上的研究进展,探讨了DNA水凝胶的分类策略,并进一步综述了DNA水凝胶在药物运输、生物传感、细胞培养等方面的应用研究。最后对DNA水凝胶未来的发展方向以及可能面临的挑战进行了展望。     

明胶微球在骨组织工程中的应用

骨组织工程通过联合利用种子细胞、生物活性因子和支架材料等要素来构建骨组织再生微环境,从而促进骨缺损的修复重建来诱导骨再生。明胶微球具有多孔性、生物降解性、生物相容性及生物安全性等优势,是一种极具应用潜能的骨修复材料。明胶微球用于体外培养种子细胞时可实现高效扩增。多官能团结构使其可作为促血管再生因子、促骨再生因子及抗感染因子等多种药物的递送载体,缓释药物的同时也可实现微球的多功能化。在构建明胶微球支架时与其他生物材料复合及血管化性能的赋予可提高支架材料的综合性能,但目前支架的设计还存在如何兼顾材料多孔结构和力学性能的问题。本文主要综述了明胶微球的常见制备技术及其近年来在骨组织工程中的应用,并对未来的发展前景进行展望。     

组织工程用纤维增强天然多糖水凝胶的进展

天然多糖水凝胶具有良好的生物相容性,然而其力学性能调节幅度小,无法满足组织工程应用巨大的需求。通过纤维增强法,不仅可显著提高天然多糖水凝胶的力学性能,还能调节复合水凝胶的降解性能、促进细胞粘附、增殖与分化行为及其组织沉积。常用的天然多糖组织工程水凝胶的纤维增强方法有物理共混法、化学作用法、静电驱动法与自组装法等。本文综述了纤维增强水凝胶的结构与功能特点,讨论了纤维增强对组织工程水凝胶的意义,以期对纤维增强组织工程水凝胶的发展起到促进作用。     

Preparation and Characterization of Electrospun PLCL/Poloxamer Nanofibers and Dextran/Gelatin Hydrogels for Skin Tissue Engineering

In this study, two different biomaterials were fabricated and their potential use as a bilayer scaffold for skin tissue engineering applications was assessed. The upper layer biomaterial was a Poly(ε-caprolactone-co-lactide)/Poloxamer (PLCL/Poloxamer) nanofiber membrane fabricated using electrospinning technology. The PLCL/Poloxamer nanofibers (PLCL/Poloxamer, 9/1) exhibited strong mechanical properties (stress/strain values of 9.37±0.38 MPa/187.43±10.66%) and good biocompatibility to support adipose-derived stem cells proliferation. The lower layer biomaterial was a hydrogel composed of 10% dextran and 20% gelatin without the addition of a chemical crosslinking agent. The 5/5 dextran/gelatin hydrogel displayed high swelling property, good compressive strength, capacity to present more than 3 weeks and was able to support cells proliferation. A bilayer scaffold was fabricated using these two materials by underlaying the nanofibers and casting hydrogel to mimic the structure and biological function of native skin tissue. The upper layer membrane provided mechanical support in the scaffold and the lower layer hydrogel provided adequate space to allow cells to proliferate and generate extracellular matrix. The biocompatibility of bilayer scaffold was preliminarily investigated to assess the potential cytotoxicity. The results show that cell viability had not been affected when cocultured with bilayer scaffold. As a consequence, the bilayer scaffold composed of PLCL/Poloxamer nanofibers and dextran/gelatin hydrogels is biocompatible and possesses its potentially high application prospect in the field of skin tissue engineering.     

Development of hydrogels for regenerative engineering

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano‐ and micro‐technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell‐matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano‐ and micro‐technologies. In addition, current hydrogel‐based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues.     

Biocompatibility of hydrogel-based scaffolds for tissue engineering applications

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds.     

Stem cells for osteoarticular and vascular tissue engineering

Tissue damages or loss of organs often result in structural and metabolic changes that can cause serious complications. The therapeutic objective of tissue engineering (TE) is to recreate, regenerate or restore function of damaged tissue. TE is based on the coalescence of three components: a scaffold or matrix from natural or synthetic origin biodegradable or not, reparative cells and signals (hypoxia, mechanical stress, morphogens…). Articular cartilage, bone and blood vessels are tissues for which TE has progressed significantly, from basic research to clinical trials. If biomaterials must exhibit different properties depending on the tissue to regenerate, the cellular component of TE is mostly represented by stem cells notably adult mesenchymal stem cells harvested from bone marrow or adipose tissue. In recent years, progress has been made in our understanding of the biological mechanisms that govern stem cell differentiation and in the development of materials with controlled physicochemical and biological properties. However, many technological barriers and regulations concerns have to be overcome before tissue engineering enters into the therapeutic arsenal of regenerative medicine. This review aims at highlighting the progress in the use of stem cells for engineering osteoarticular and vascular tissues.     

Stiffness of photocrosslinkable gelatin hydrogel influences nucleus pulposus cell propertiesin vitro

A key early sign of degenerative disc disease (DDD) is the loss of nucleus pulposus (NP) cells (NPCs). Accordingly, NPC transplantation is a treatment strategy for intervertebral disc (IVD) degeneration. However, in advanced DDD, due to structural damage of the IVD and scaffold mechanical properties, the transplanted cells are less viable and secrete less extracellular matrix, and thus, are unable to efficiently promote NP regeneration. In this study, we evaluated the encapsulation of NPCs in a photosensitive hydrogel made of collagen hydrolysate gelatin and methacrylate (GelMA) to improve NP regeneration. By adjusting the concentration of GelMA, we prepared hydrogels with different mechanical properties. After examining the mechanical properties, cell compatibility and tissue engineering indices of the GelMA-based hydrogels, we determined the optimal hydrogel concentration of the NPC-encapsulating GelMA hydrogel for NP regeneration as 5%. NPCs effectively combined with GelMA and proliferated. As the concentration of the GelMA hydrogel increased, the survival, proliferation and matrix deposition of the encapsulated NPCs gradually decreased, which is the opposite of NPCs grown on the surface of the hydrogel. The controllability of the GelMA hydrogels suggests that these NPC-encapsulating hydrogels are promising candidates to aid in NP tissue engineering and repairing endogenous NPCs.     

Highly extensible, tough, and elastomeric nanocomposite hydrogels from poly(ethylene glycol) and hydroxyapatite nanoparticles

Unique combinations of hard and soft components found in biological tissues have inspired researchers to design and develop synthetic nanocomposite gels and hydrogels with elastomeric properties. These elastic materials can potentially be used as synthetic mimics for diverse tissue engineering applications. Here we present a set of elastomeric nanocomposite hydrogels made from poly(ethylene glycol) (PEG) and hydroxyapatite nanoparticles (nHAp). The aqueous nanocomposite PEG-nHAp precursor solutions can be injected and then covalently cross-linked via photopolymerization. The resulting PEG-nHAp hydrogels have interconnected pore sizes ranging from 100 to 300 nm. They have higher extensibilities, fracture stresses, compressive strengths, and toughness when compared with conventional PEO hydrogels. The enhanced mechanical properties are a result of polymer nanoparticle interactions that interfere with the permanent cross-linking of PEG during photopolymerization. The effect of nHAp concentration and temperature on hydrogel swelling kinetics was evaluated under physiological conditions. An increase in nHAp concentration decreased the hydrogel saturated swelling degree. The combination of PEG and nHAp nanoparticles significantly improved the physical and chemical hydrogel properties as well as some biological characteristics such as osteoblast cell adhesion. Further development of these elastomeric materials can potentially lead to use as a matrix for drug delivery and tissue repair especially for orthopedic applications.     

Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part II: biofunctional characteristics

We present here the biological performance in supporting tissue regeneration of hybrid hydrogels consisting of genetically engineered protein polymers that carry specific features of the natural extracellular matrix, cross-linked with reactive poly(ethylene glycol) (PEG). Specifically, the protein polymers contain the cell adhesion motif RGD, which mediates integrin receptor binding, and degradation sites for plasmin and matrix-metalloproteinases, both being proteases implicated in natural matrix remodeling. Biochemical assays as well as in vitro cell culture experiments confirmed the ability of these protein-PEG hydrogels to promote specific cellular adhesion and to exhibit degradability by the target enzymes. Cell culture experiments demonstrated that proteolytic sensitivity and suitable mechanical properties were critical for three-dimensional cell migration inside these synthetic matrixes. In vivo, protein-PEG matrixes were tested as a carrier of bone morphogenetic protein (rhBMP-2) to heal critical-sized defects in a rat calvarial defect model. The results underscore the importance of fine-tuning material properties of provisional therapeutic matrixes to induce cellular responses conducive to tissue repair. In particular, a lack of rhBMP or insufficient degradability of the protein-PEG matrix prevented healing of bone defects or remodeling and replacement of the artificial matrix. This work confirms the feasibility of attaining desired biological responses in vivo by engineering material properties through the design of single components at the molecular level. The combination of polymer science and recombinant DNA technology emerges as a powerful tool for the development of novel biomaterials.