Serban Monica A, Prestwich Glenn D
Department of Medicinal Chemistry and Center of Therapeutic Biomaterials, The University of Utah, 419 Wakara Way, Salt Lake City, UT 84108-1257, USA.
Methods. 2008 May;45(1):93-8. doi: 10.1016/j.ymeth.2008.01.010.
The common technique of growing cells in two-dimensions (2-D) is gradually being replaced by culturing cells on matrices with more appropriate composition and stiffness, or by encapsulation of cells in three-dimensions (3-D). The universal acceptance of the new 3-D paradigm has been constrained by the absence of a commercially available, biocompatible material that offers ease of use, experimental flexibility, and a seamless transition from in vitro to in vivo applications. The challenge-the puzzle that needs a solution-is to replicate the complexity of the native extracellular matrix (ECM) environment with the minimum number of components necessary to allow cells to rebuild and replicate a given tissue. For use in drug discovery, toxicology, cell banking, and ultimately in reparative medicine, the ideal matrix would therefore need to be highly reproducible, manufacturable, approvable, and affordable. Herein we describe the development of a set of modular components that can be assembled into biomimetic materials that meet these requirements. These semi-synthetic ECMs, or sECMs, are based on hyaluronan derivatives that form covalently crosslinked, biodegradable hydrogels suitable for 3-D culture of primary and stem cells in vitro, and for tissue formation in vivo. The sECMs can be engineered to provide appropriate biological cues needed to recapitulate the complexity of a given ECM environment. Specific applications for different sECM compositions include stem cell expansion with control of differentiation, scar-free wound healing, growth factor delivery, cell delivery for osteochondral defect and liver repair, and development of vascularized tumor xenografts for personalized chemotherapy.
在二维（2-D）环境中培养细胞的传统技术正逐渐被在具有更合适成分和硬度的基质上培养细胞，或在三维（3-D）环境中封装细胞所取代。新型三维模式尚未得到广泛应用，原因在于缺乏一种具备易用性、实验灵活性且能实现从体外到体内应用无缝过渡的生物相容性商用材料。当前面临的挑战——亟待解决的难题——是要用最少的成分来复制天然细胞外基质（ECM）环境的复杂性，从而使细胞能够重建并复制特定组织。因此，对于药物研发、毒理学、细胞库乃至最终的修复医学而言，理想的基质需要具备高度可重复性、可制造性、可审批性且价格合理。在此，我们描述了一组模块化组件的开发情况，这些组件可组装成满足上述要求的仿生材料。这些半合成ECM，即sECM，基于透明质酸衍生物，可形成共价交联、可生物降解的水凝胶，适用于原代细胞和干细胞的三维体外培养以及体内组织形成。sECM可以通过设计来提供重现特定ECM环境复杂性所需的适当生物学信号。不同sECM组成的具体应用包括控制分化的干细胞扩增、无瘢痕伤口愈合、生长因子递送、用于骨软骨缺损和肝脏修复的细胞递送，以及用于个性化化疗的血管化肿瘤异种移植的开发。
