Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments

This article provides an overview on the application of metallic ions in the fields of regenerative medicine and tissue engineering, focusing on their therapeutic applications and the need to design strategies for controlling the release of loaded ions from biomaterial scaffolds. A detailed summary of relevant metallic ions with potential use in tissue engineering approaches is presented. Remaining challenges in the field and directions for future research efforts with focus on the key variables needed to be taken into account when considering the controlled release of metallic ions in tissue engineering therapeutics are also highlighted.     

壳聚糖支架在组织工程中的应用

综述了壳聚糖作为细胞生长载体在软骨组织工程，骨组织工程和皮肤组织工程等方面的应用进展，表明壳聚糖有望成为优异的组织工程支架材料。     

Electrospun nanofibrous materials for tissue engineering and drug delivery

Abstract

The electrospinning technique, which was invented about 100 years ago, has attracted more attention in recent years due to its possible biomedical applications. Electrospun fibers with high surface area to volume ratio and structures mimicking extracellular matrix (ECM) have shown great potential in tissue engineering and drug delivery. In order to develop electrospun fibers for these applications, different biocompatible materials have been used to fabricate fibers with different structures and morphologies, such as single fibers with different composition and structures (blending and core-shell composite fibers) and fiber assemblies (fiber bundles, membranes and scaffolds). This review summarizes the electrospinning techniques which control the composition and structures of the nanofibrous materials. It also outlines possible applications of these fibrous materials in skin, blood vessels, nervous system and bone tissue engineering, as well as in drug delivery.     

骨组织工程多孔支架材料性质及制备技术

多孔性生物可降解支架的选择和制备是组织工程技术成功运用的关键。从骨架的材料要求、常用的骨架材料、骨架的制备技术等几个方面对组织工程和生物降解支架的研究进行了综述 ,并对该研究的前景进行了展望     

组织工程用高分子骨架研究的进展

组织工程是一个新兴的交叉学科。结合目前组织工程用高分子骨架研究和发展的最新状况，探讨了高分子骨架材料的本体结构、性能及表面形态与分子结构要求，并对常用的骨架制备方法进行了概述。     

聚乳酸组织工程支架表面涂覆钙磷盐的工艺研究

提出了以聚乳酸／钙磷盐／胶原的骨组织工程支架快速成形制造的材料系统，对比了两种在聚乳酸(PLA)表面涂覆钙磷盐的工艺．一种是将聚乳酸组织工程支架浸泡在模拟体液中采用平衡反应法沉积钙磷盐；另一种是在聚乳酸薄膜上采用非平衡反应法沉积钙磷盐；系统地研究了沉积时间和沉积量、钙磷摩尔比和相结构演变的关系；通过控制反应时间和调整反应物配比获得磷酸四钙(TetCP)-PLA和无定形磷酸钙(ACP)—PLA等材料组合；并对所获得的复合材料进行生物相容性试验．对比试验证明细胞在材料表面生长良好，采用两种方法涂覆钙磷盐均改进了聚乳酸的生物相容性．     

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.     

Preparation of poly(3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds for bone tissue engineering

Poly(3-hydroxybutyrate)/nano-hydroxyapatite (PHB/nHA) composite scaffolds were fabricated via powder mixing, compression moulding, and particle leaching technique. The scaffolds had high porosity with interconnected porous architecture, a favorable structure for cell attachment and new bone tissue ingrowth. A homogeneous dispersion and a uniform distribution of HA nanoparticles in the polymer matrix were obtained. The scaffolds exhibited improved compressive modulus and compressive strength, which were all in the range of compressive modulus and compressive strength of cancellous bone. In addition, the use of toxic organic solvents was eliminated. Thus, the fabricated PHB/nHA composite scaffolds tend to be promising for application in bone tissue engineering.     

Biomanufacturing for tissue engineering: Present and future trends

Tissue engineering, often referred to as regenerative medicine and reparative medicine, is an interdisciplinary field that necessitates the combined effort of cell biologists, engineers, material scientists, mathematicians, geneticists, and clinicians toward the development of biological substitutes that restore, maintain, or improve tissue function. It has emerged as a rapidly expanding approach to address the organ shortage problem and comprises tissue regeneration and organ substitution. Cells placed on/or within constructs is the most common strategy in tissue engineering. Successful cell seeding depends on fast attachment of cell to scaffolds, high cell survival and uniform cell distribution. The seeding time is strongly dependent on the scaffold material and architecture. Scaffolds provide an initial biochemical substrate for the novel tissue until cells can produce their own extra-cellular matrix (ECM). Thus scaffolds not only define the 3D space for the formation of new tissues, but also serve to provide tissues with appropriate functions. These scaffolds are often critical, both in vivo (within the body) or in vitro (outside the body) mimicking in vivo conditions. Additive fabrication processes represent a new group of non-conventional fabrication techniques recently introduced in the biomedical engineering field. In tissue engineering, additive fabrication processes have been used to produce scaffolds with customised external shape and predefined internal morphology, allowing good control of pore size and pore distribution. This article provides a comprehensive state-of-the-art review of the application of biomanufacturing additive processes in the field of tissue engineering. New and moving trends in biomanufacturing technologies and the concept of direct cell-printing technologies are also discussed.     

Alternative tissue engineering scaffolds based on starch: processing methodologies, morphology, degradation and mechanical properties

An ideal tissue engineering scaffold must be designed from a polymer with an adequate degradation rate. The processing technique must allow for the preparation of 3-D scaffolds with controlled porosity and adequate pore sizes, as well as tissue matching mechanical properties and an appropriate biological response.

This communication revises recent work that has been developed in our laboratories with the aim of producing 3-D polymeric structures (from starch-based blends) with adequate properties to be used as scaffolds for bone tissue engineering applications. Several processing methodologies were originally developed and optimised. Some of these methodologies were based on conventional melt-based processing routes, such as extrusion using blowing agents (BA) and compression moulding (combined with particulate leaching). Other developed technologies included solvent casting and particle leaching and an innovative in situ polymerization method.

By means of using the described methodologies, it is possible to tailor the properties of the different scaffolds, namely their degradation, morphology and mechanical properties, for several applications in tissue engineering. Furthermore, the processing methodologies (including the blowing agents used in the melt-based technologies) described above do not affect the biocompatible behaviour of starch-based polymers. Therefore, scaffolds obtained from these materials by means of using one of the described methodologies may constitute an important alternative to the materials currently used in tissue engineering.     

3D-macroporous hybrid scaffolds for tissue engineering: Network design and mathematical modeling of the degradation kinetics

In the present study it is reported the synthesis, characterization and subsequent degradation performance of organic-inorganic hybrid systems chemically modified by bi-functional crosslinker (glutaraldehyde, GA). The hybrids were prepared by combining 70% poly (vinyl alcohol) and 30% bioactive glass (58SiO₂-33CaO-9P₂O₅, BaG) via sol-gel route using foaming-casting method producing different macroporous tri-dimensional scaffolds depending on the degree of network crosslinking. The in vitro degradation kinetics was evaluated by measuring the mass loss upon soaking into de-ionized water at 37 °C for up to 21 days and different mathematical models were tested. The PVA/BaG hybrids scaffolds properties “as-synthesized” and after the degradation process were extensively characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), mechanical compressing tests and X-ray Micro-computed Tomography analysis (μCT). The results have clearly shown the effectiveness of tailoring the PVA/BaG hybrids properties and degradation kinetics mechanisms by chemically engineering the structure at nano-order level using different concentrations of the crosslinker. Moreover, these hybrid crosslinked nanostructures have shown 3D hierarchical pore size with interconnected architecture within the range of 10-450 μm for potential use in the field of bone regenerative medicine.     

Biomaterials in orthopaedics

At present, strong requirements in orthopaedics are still to be met, both in bone and joint substitution and in the repair and regeneration of bone defects. In this framework, tremendous advances in the biomaterials field have been made in the last 50 years where materials intended for biomedical purposes have evolved through three different generations, namely first generation (bioinert materials), second generation (bioactive and biodegradable materials) and third generation (materials designed to stimulate specific responses at the molecular level). In this review, the evolution of different metals, ceramics and polymers most commonly used in orthopaedic applications is discussed, as well as the different approaches used to fulfil the challenges faced by this medical field.     

Characterization of poly(3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds fabricated without the use of organic solvents for bone tissue engineering applications

Poly(3-hydroxybutyrate)/nano-hydroxyapatite (PHB/nHA) composite scaffolds were fabricated without the use of organic solvents at different mass fractions of HA nanoparticles. HA nanoparticles were homogeneously dispersed as primary particles in the polymer matrix of the scaffolds at 10 and 15 wt.% nHA content. Agglomeration of HA nanoparticles occurred when the nHA content of the scaffolds reached 20 wt.%. All the scaffolds had high porosities with interconnected porous structure and optimized pore size ranges. Mechanical properties of all the scaffolds were in the range of mechanical properties of cancellous bone. Scaffolds were biocompatible to MG-63 cells in the indirect method of cytotoxicity evaluation. Also, the morphology of the attached MG-63 cells in direct contact with the scaffolds indicated the appropriate cell-scaffold interaction. Thus, the PHB/nHA composite scaffolds investigated in this study tend to be favorable for bone tissue engineering applications.     

骨软骨组织工程仿生梯度支架研究进展

骨软骨缺损是导致关节发病和残疾的重要原因,骨软骨组织工程是修复骨软骨缺损的方法之一。骨软骨组织工程方法涉及仿生梯度支架的制造,该支架需模仿天然骨软骨组织的生理特性（例如从软骨表面到软骨下骨之间的梯度过渡）。在许多研究中骨软骨仿生梯度支架表现为离散梯度或连续梯度,用于模仿骨软骨组织的特性,例如生物化学组成、结构和力学性能。连续型骨软骨梯度支架的优点是其每层之间没有明显的界面,因此更相似地模拟天然骨软骨组织。到目前为止,骨软骨仿生梯度支架在骨软骨缺损修复研究中已经取得了良好的实验结果,但是骨软骨仿生梯度支架与天然骨软骨组织之间仍然存在差异,其临床应用还需要进一步研究。本文首先从骨软骨缺损的背景、微尺度结构与力学性能、骨软骨仿生梯度支架制造相关的材料与方法等方面概述了离散和连续梯度支架的研究进展。其次,由于3D打印骨软骨仿生梯度支架的方法能够精确控制支架孔的几何形状和力学性能,因此进一步介绍了计算仿真模型在骨软骨组织工程中的应用,例如采用仿真模型优化支架结构和力学性能以预测组织再生。最后,提出了骨软骨缺损修复相关的挑战以及骨软骨组织再生未来研究的展望。例如,连续型骨软骨仿生梯度支架需要更相似地模拟天然骨软骨组织单元的结构,即力学性能和生化性能的过渡更加自然地平滑。同时,虽然大多数骨软骨仿生梯度支架在体内外实验中均取得了良好的效果,但临床研究和应用仍然需要进行进一步深入研究。