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．     

Cellular responses in exertion-induced skeletal muscle injury

Muscle injury is a common result of muscle exertion caused by overload and over-activity. In this presentation, an attempt was made to discuss models of muscle injury which involve exertion but not excessive strain, although most functional activities of the extremities require some eccentric muscle actions. Muscle injury is characterized by cellular and extracellular matrix responses which appear to be common to all types of muscle trauma - even in the absence of bleeding. Using tenotomy and functional over-load of the rat hindlimb muscles as examples, illustrations of several of these responses are presented and discussed.     

Strain gradient development in 3-dimensional extracellular matrix scaffolds during in vitro mechanical stimulation

This study analyzed strain variations in 3D ECM scaffolds using a membrane-adherent model (MM) and a direct elongation model (DM). Computational models were solved for target strains from 1 to 10% at varied scaffold thicknesses and intra-scaffold slices. DM strain profiles were uniform within the scaffold and independent of thickness. However, a wide range of strains developed with substantial volume experiencing significantly off-target strain. MM strain profiles varied throughout the scaffold, exhibiting significantly reduced average strain with increasing thickness. These findings are important for tissue engineering studies since biological responses are commonly attributed to a single strain level that only partially describes the mechanical condition, making it difficult to develop precise causal relationships. Spatial strain variations and reduced average strain may warrant targeted sampling for cell response and should be taken into consideration by investigators using large-volume 3D scaffolds when engineering mechanically sensitive tissues.     

Engineered Smooth Muscle Tissues: Regulating Cell Phenotype with the Scaffold

Culturing cells on three-dimensional, biodegradable scaffolds may create tissues suitable either for reconstructive surgery applications or as novel in vitro model systems. In this study, we have tested the hypothesis that the phenotype of smooth muscle cells (SMCs) in three-dimensional, engineered tissues is regulated by the chemistry of the scaffold material. Specifically, we have directly compared cell growth and patterns of extracellular matrix (ECM) (e.g. , elastin and collagen) gene expression on two types of synthetic polymer scaffolds and type I collagen scaffolds. The growth rates of SMCs on the synthetic polymer scaffolds were significantly higher than on type I collagen sponges. The rate of elastin production by SMCs on polyglycolic acid (PGA) scaffolds was 3.5 +/- 1.1-fold higher than that on type I collagen sponges on Day 11 of culture. In contrast, the collagen production rate on type I collagen sponges was 3.3 +/- 1.1-fold higher than that on PGA scaffolds. This scaffold-dependent switching between elastin and collagen gene expression was confirmed by Northern blot analysis. The finding that the scaffold chemistry regulates the phenotype of SMCs independent of the scaffold physical form was confirmed by culturing SMCs on two-dimensional films of the scaffold materials. It is likely that cells adhere to these scaffolds via different ligands, as the major protein adsorbed from the serum onto synthetic polymers was vitronectin, whereas fibronectin and vitronectin were present at high density on type I collagen sponges. In summary, this study demonstrates that three-dimensional smooth muscle-like tissues can be created by culturing SMCs on three-dimensional scaffolds, and that the phenotype of the SMCs is strongly regulated by the scaffold chemistry. These engineered tissues provide novel, three-dimensional models to study cellular interaction with ECM in vitro.     

Coupling of cell structure to cell metabolism and function

The fact that cells make directed decisions regarding how to use energy, i.e., where to direct intracellular particles or where to move, suggests that energy can be, and is, harnessed in specific ways. It is now well established that the chemical reactions of the cell do not occur in nonorganized soup, but rather in the context of ordered structure. The physical components that make up this ordered structure of the cell are part of the tissue matrix, which consists of the dynamic linkages between the skeletal networks of the nucleus (the nuclear matrix), the cytoplasm (the cytoskeleton), and the extracellular environment (the extracellular matrix). To understand gene function and how the energy of the cell is directed towards accomplishing the tasks directed by DNA (gene expression), a further understanding of how cell structure is tied to cellular energy and function is required. We propose that the structural components of the cell harness cellular energy to direct cell functions by providing a dynamic bridge between thermodynamics and gene expression. © 1994 Wiley-Liss, Inc.     

Biological matrices and bionanotechnology

A crucial step towards the goal of tissue engineering a heart valve will be the choice of scaffold onto which an appropriate cell phenotype can be seeded. Successful scaffold materials should be amenable to modification, have a controlled degradation, be compatible with the cells, lack cytotoxicity and not elicit an immune or inflammatory response. In addition, the scaffold should induce appropriate responses from the cells seeded onto it, such as cell attachment, proliferation and remodelling capacity, all of which should promote the formation of a tissue construct that can mimic the structure and function of the native valve. This paper discusses the various biological scaffolds that have been considered and are being studied for use in tissue engineering a heart valve. Also, strategies to enhance the biological communication between the scaffold and the cells seeded onto it as well as the use of bionanotechnology in the manufacture of scaffolds possessing the desired properties will be discussed.