Large-Scale Production of 3D Bioactive Glass Macroporous Scaffolds for Tissue Engineering

For tissue engineering applications, a scaffold is required that can act as a template and guide for cell proliferation, cell differentiation and tissue growth. Interconnected pores with diameters greater than 100 m are required for tissue ingrowth, vascularisation and nutrient delivery to the centre of the scaffold. 3D bioactive glass scaffolds have been produced, by foaming sol-gel derived bioactive glasses. The method to produce foams with a modal macropore diameter of 100 m, and a handling strength suitable for cell culture, was to foam 50 ml batches of sol with the aid of a surfactant and gelling agent. In vitro and in vivo tests show that the scaffolds have high potential to be used in bone tissue engineering applications. Larger batches are required to produce scaffolds commercially. The aim of this work was to investigate how the process could be up-scaled for commercial use. This study shows that foaming larger aliquots of sol decreased the scaffold porosity and interconnectivity and investigates methods of modifying the process to obtain large quantities of foam scaffolds with pores in excess of 100 m. The optimum method to produce foams of similar pore structure from 200 ml sol to those produced from 50 ml sol comprised of adding 3 ml surfactant and 12 ml dionised water to the sol to start foaming and injecting a gas mixture (70% helium, 30% nitrogen) at 0.2 bar while applying vigorous agitation.     

Polysaccharides and Their Derivatives for Versatile Tissue Engineering Application

Research and development in the design, synthesis, modification, evaluation, and characterization of polysaccharide‐based bioactive polymeric materials for guiding and promoting new tissue in‐growth is reviewed. Emphasis is given in this interdisciplinary field of tissue engineering (TE) with particular reference to bone, cartilage, and skin TE. Current strategies in scaffold‐guided TE approaches using polymers of natural origin and their composites are elaborated. Innovative modification techniques in creating functional materials for advanced TE applications are presented. Challenges and possible solutions in the technological innovation in factor molecules incorporation and surface functionalization for improving the fabrication of biomaterials scaffolds for cost‐effective TE are also presented.

     

Processing-structure-property relationships of electrospun PLA-PEO membranes reinforced with enzymatic cellulose nanofibers

Three different solvent mixtures were used to prepare electrospun membranes based on polylactic acid (PLA), polyethylene oxide (PEO) and enzymatic cellulose nanofibers (CNF). The materials were characterized from a morphological, spectroscopic, mechanical and rheological point of view. Furthermore, swelling test were performed in order to assess the water uptake of each sample.The results put into evidence that the choice of the solvents affects the structure and the properties of the membranes. Among the protocols tested, using chloroform/acetone/ethanol mixture was found to allow a high degree of CNF dispersion and a good electrospinnability of polymer solutions. These features led to membranes with impressive improvement of mechanical properties (+350% in stiffness, +350% in tensile strength and +500% in toughness) with respect to those of PLA/PEO and dramatically increased the water uptake of these materials (up to +350% within 120 min).     

Biodegradable Polyesters for Tissue Engineering

Summary: Paper describes basic characteristics of synthesis and properties of aliphatic polyesters used for tissue engineering. Described is also synthesis of polyester containing block copolymers suitable for surface modification. Described are methods used for scaffold fabrication with required porosity. In particular, presented are methods according to which scaffolds are made from prefabricated polyester micro- and nanoparticles.     

Self-Hardening Hydrogel for Bone Tissue Engineering

Summary: We have developed a self-reticulating polymer based on silanized hydroxypropylmethylcellulose (Si-HPMC). The aim of this study was to determine whether this Si-HPMC hydrogel with or without calcium phosphate granules could represent a potential scaffold for bone tissue engineering. This study showed that Si-HPMC hydrogel didn't affect SaOS-2 and rat bone marrow cells viability. In addition, SaOS-2 cells are able to proliferate within Si-HPMC hydrogel containing or not calcium phosphate granules whereas Rat bone marrow cells proliferate only at the surface of calcium phosphate granules contained within Si-HPMC hydrogel. Finally, SaOS-2 cells seeded at the surface of reticulated Si-HPMC were not able to penetrate the hydrogel, while J774, a macrophage cells line, were able to move into the Si-HPMC hydrogel. These data indicate that Si-HPMC is a promissing scaffold for tissue engineering.     

Multi-Material Scaffolds for Tissue Engineering

A trend in developing biocompatible scaffolds for tissue engineering has been to seek an ideal single material for which a given cell type will exhibit favorable behavior. While an ideal single material has proven elusive, scaffold manufacture using combinations of specialist materials can produce more versatile structures. By controlling the percentage and architecture of material components, mechanical properties, cell attachment, and proliferation may be optimized for a given function. Three specialist materials, poly-ϵ-caprolactone (PCL), fibrin, and alginate, were incorporated into multi-component scaffolds for a series of experiments testing each component with culture of fibroblasts. The rigid and formable PCL provided structure, the fibrin pore-filler allowed for cell attachment, and alginate thread provided a nutrient transfer pathway in lieu of a vascular system. The efficacy of these scaffolds was judged on fibroblast distribution and population after 7-12 days of culture.     

Scaffold Design for Tissue Engineering

Tissue engineering has emerged as a promising alternative approach in the treatment of malfunctioning or lost organs. In this approach, a temporary scaffold is needed to serve as an adhesive substrate for the implanted cells and a physical support to guide the formation of the new organs. In addition to facilitating cell adhesion, promoting cell growth, and allowing the retention of differentiated cell functions, the scaffold should be biocompatible, biodegradable, highly porous with a large surface/volume ratio, mechanically strong, and malleable. A number of three‐dimensional porous scaffolds fabricated from various kinds of biodegradable materials have been developed. This paper reviews some of the advances in scaffold design focusing on the hybrid scaffolds recently developed in the authors' laboratory.     

Silk Fibroin-Based Biomaterials for Tissue Engineering Applications

Tissue engineering (TE) involves the combination of cells with scaffolding materials and appropriate growth factors in order to regenerate or replace damaged and degenerated tissues and organs. The scaffold materials serve as templates for tissue formation and play a vital role in TE. Among scaffold materials, silk fibroin (SF), a naturally occurring protein, has attracted great attention in TE applications due to its excellent mechanical properties, biodegradability, biocompatibility, and bio-absorbability. SF is usually dissolved in an aqueous solution and can be easily reconstituted into different forms, including films, mats, hydrogels, and sponges, through various fabrication techniques, including spin coating, electrospinning, freeze drying, and supercritical CO₂-assisted drying. Furthermore, to facilitate the fabrication of more complex SF-based scaffolds, high-precision techniques such as micro-patterning and bio-printing have been explored in recent years. These processes contribute to the diversity of surface area, mean pore size, porosity, and mechanical properties of different silk fibroin scaffolds and can be used in various TE applications to provide appropriate morphological and mechanical properties. This review introduces the physicochemical and mechanical properties of SF and looks into a range of SF-based scaffolds that have recently been developed. The typical applications of SF-based scaffolds for TE of bone, cartilage, teeth and mandible tissue, cartilage, skeletal muscle, and vascular tissue are highlighted and discussed followed by a discussion of issues to be addressed in future studies.     

组织工程用水凝胶材料

综述了目前用于组织工程支架材料的水凝胶,包括胶原和明胶、透明质酸盐、海藻酸盐,琼脂糖和壳聚糖等天然水凝胶,聚丙烯酸及其衍生物、聚氧化乙烯及其衍生共聚物、聚乙烯醇、聚磷腈和合成多肽等合成水凝胶,并介绍了可注射性组织工程水凝胶。     

Polymeric Scaffolds for Cartilage Tissue Engineering

Polymeric scaffolds are three-dimensional, porous structures that may be used as a vehicle to deliver cells or therapeutic factors to repair tissue defects. Both biodegradable and non-biodegradable polymers have been developed for this purpose. In this review, we survey the polymers that have been investigated for cartilage tissue engineering and discuss the critical parameters for successful applications in the future.     

Injectable Hydrogels for Cardiac Tissue Engineering

In light of the limited efficacy of current treatments for cardiac regeneration, tissue engineering approaches have been explored for their potential to provide mechanical support to injured cardiac tissues, deliver cardio‐protective molecules, and improve cell‐based therapeutic techniques. Injectable hydrogels are a particularly appealing system as they hold promise as a minimally invasive therapeutic approach. Moreover, injectable acellular alginate‐based hydrogels have been tested clinically in patients with myocardial infarction (MI) and show preservation of the left ventricular (LV) indices and left ventricular ejection fraction (LVEF). This review provides an overview of recent developments that have occurred in the design and engineering of various injectable hydrogel systems for cardiac tissue engineering efforts, including a comparison of natural versus synthetic systems with emphasis on the ideal characteristics for biomimetic cardiac materials.     

组织工程相关生物材料表面工程的研究进展

生物材料用作人工细胞外基质(ECM ) 在组织工程中占据重要位置。本文在分析细胞2生物材料表面相互作用的基础上, 从生物材料中的水、材料表面的形态、材料表面的特异性识别及生物材料诱发愈合等方面探讨了生物材料的复杂性。生物材料对细胞的影响是一个双向、动态过程, 起着调节细胞增殖和凋亡平衡的作用。基于生物材料对细胞生长的影响, 本文提出了生物材料表面生物仿生化以提高细胞亲和力,糖链团簇、糖脂质及材料表面蛋白质修饰以提高细胞特异性识别, 材料表面的自组装修饰以改善表面形态等观点。     

Development of Channeled Nanofibrous Scaffolds for Oriented Tissue Engineering

A tissue‐engineering scaffold resembling the structure of the natural extracellular matrix can often facilitate tissue regeneration. Nerve and tendon are oriented micro‐scale tissue bundles. In this study, a method combining injection molding and thermally induced phase separation techniques is developed to create single‐ and multiple‐channeled nanofibrous poly(L ‐lactic acid) scaffolds. The overall shape, the number and spatial arrangement of channels, the channel wall matrix architecture, the porosity and mechanical properties of the scaffolds are all tunable. The porous NF channel wall matrix provides an excellent microenvironment for protein adsorption and the attachment of PC12 neuronal cells and tendon fibroblast cells, showing potential for neural and tendon tissue regeneration.

     

可降解聚氨酯型组织工程多孔支架材料的制备

本文在可降解型聚氨酯分子设计,聚氨酯型组织工程支架制备方法,可降解聚氨酯多孔支架的生物学性能及可降解聚氨酯多孔支架在组织工程中的应用等几个方面对可降解聚氨酯型组织工程支架的最新研究进展作了综述。重点讨论了静电纺丝、冷冻干燥、相分离等几种聚氨酯多孔支架制备方法以及聚氨酯型组织工程支架的生物降解性质、生长因子嵌入、生物力学性能、生物相容性等生物学性能。目前的研究表明通过聚氨酯分子设计与各种支架制备方法结合可制得满足各种生物学性能的支架材料且这类材料已被证实在血管、软骨、硬质骨等各类组织工程中有重要的应用价值。但如何进一步提高聚氨酯支架材料的力学强度以使其能更好地与硬组织的力学性能相匹配以及如何降低或消除聚氨酯对人体的毒性仍是需要进一步研究的问题。     

Functionalization of Biodegradable Polyester for Tissue Engineering Applications

Summary: Chemical modification of polymer surface may potentially be used to create smart materials that can guide cellular adhesion, proliferation and maintenance of specific expression of molecules. The microbial polyester poly (3-hydroxybutyrate) (PHB) has been attracted attention as promising material for applications in tissue engineering. In this work, a wet-chemical method, base ethylenediamine aminolysis, was performed to improve the adhesion of chondrocytes isolated from human articular cartilage to PHB films. The effects of chemical treatment on PHB films was evaluated by following changes in morphology and surface chemical composition using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS), respectively. While the effect on cells morphology was studied by scanning electron microscopy (SEM). The treatment with ethylenediamine did not change significantly the morphology of the structures of PHB films surface. However, the roughness of the aminolyzed films was slightly higher. The introduction of nitrogen-containing groups was confirmed by XPS. In vitro experiments indicated that the surface modification did not have toxic effects in cells, since they could adhere and proliferate on modified PHB films. It was observed that long-time treatment improved ability of PHB films to support cell growth, which could be accounted to physicochemical and topological effects.     

骨组织工程支架材料研究进展*

骨在组织工程中得到了非常广泛、深入的研究.支架材料与许多可降解材料一起也在进行探索性研究.用于骨组织工程的生物材料可以是三维多孔的刚硬材料,也可以是可注射材料.本文从聚合物角度综述了骨组织工程对支架材料的基本要求,用于骨组织工程的可降解生物材料、支架材料的设计和制备技术以及支架材料的表面修饰等方面的研究进展.     

壳聚糖及其衍生物在组织工程中的应用

壳聚糖由于具有良好的生物相容性、生物可降解性以及具有可反应的活性基团,因而在生物、医学等领域具有广泛的研究和应用。随着组织工程学研究的深入,壳聚糖及其衍生物材料作为天然高分子组织工程支架越来越受到重视,综述了近年来国内外壳聚糖及其衍生物在组织工程上的研究和应用情况,包括壳聚糖及其衍生物支架材料的制备方法、壳聚糖的改性以及壳聚糖复合材料等。     

Composite Fiber Spun Mat Synthesis and In Vitro Biocompatibility for Guide Tissue Engineering

Composite scaffolds are commonly used strategies and materials employed to achieve similar analogs of bone tissue. This study aims to fabricate 10% wt polylactic acid (PLA) composite fiber scaffolds by the air-jet spinning technique (AJS) doped with 0.5 or 0.1 g of zirconium oxide nanoparticles (ZrO₂) for guide bone tissue engineering. ZrO₂ nanoparticles were obtained by the hydrothermal method and characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). SEM and fourier-transform infrared spectroscopy (FTIR) analyzed the synthesized PLA/ZrO₂ fiber scaffolds. The in vitro biocompatibility and bioactivity of the PLA/ZrO₂ were studied using human fetal osteoblast cells. Our results showed that the hydrothermal technique allowed ZrO₂ nanoparticles to be obtained. SEM analysis showed that PLA/ZrO₂ composite has a fiber diameter of 395 nm, and the FITR spectra confirmed that the scaffolds’ chemical characteristics are not affected by the synthesized technique. In vitro studies demonstrated that PLA/ZrO₂ scaffolds increased cell adhesion, cellular proliferation, and biomineralization of osteoblasts. In conclusion, the PLA/ZrO₂ scaffolds are bioactive, improve osteoblasts behavior, and can be used in tissue bone engineering applications.