In tissue engineering and regenerative medicine, a biomaterial provides mechanical support and biochemical signals to encourage cell attachment and modulate cell behaviour. Nature’s template for a biomaterial is the extracellular matrix (ECM). The ECM contains intrinsic biochemical and mechanical cues that regulate cell phenotype and function in development, in homeostasis and in response to injury. The use of ECM-based materials in biomedical research has advanced from coating cell culture plates with purified ECM components to the design of ECM-mimicking biomaterials and the engineering of decellularized tissues aimed at recapitulating the dynamics, composition and structure of the ECM. In this Review, we highlight important matrix properties and functions in the context of tissue engineering and regenerative medicine, consider techniques such as proteomics for the investigation of matrix structure and composition and discuss different engineering strategies for the design of matrix-mimicking biomaterials. Tissue, whole organ and cell culture decellularization approaches are examined for their potential to preserve the tissue-specific biochemical composition and ultrastructure of the ECM and for the development of biomaterials that promote the formation of functional tissues in clinical applications. Finally, we investigate challenges and opportunities of ECM biomaterials for the design of organotypic models to study disease progression, for the ex vivo creation of engineered tissue and for the clinical translation of functional tissue reconstruction strategies in vivo.

在组织工程和再生医学中，生物材料提供机械支持和生化信号，以鼓励细胞附着并调节细胞行为。生物材料的自然模板是细胞外基质（ECM）。ECM包含内在的生化和机械线索，可调节细胞表型和发育，体内稳态以及对损伤的反应。基于ECM的材料在生物医学研究中的应用已从用纯化的ECM成分包被细胞培养板到模仿ECM的生物材料的设计以及旨在概括ECM的动力学，组成和结构的脱细胞组织工程。在这篇综述中，我们重点介绍了组织工程学和再生医学领域中重要的基质特性和功能，考虑研究蛋白质组学等技术来研究基质的结构和组成，并讨论设计类似基质的生物材料的不同工程策略。检查了组织，整个器官和细胞培养物的脱细胞方法在保存ECM的组织特异性生化成分和超微结构方面的潜力以及在临床应用中促进功能性组织形成的生物材料的开发。最后，我们调查了ECM生物材料在设计器官模型以研究疾病进展，离体创建工程组织以及体内功能组织重建策略的临床翻译方面所面临的挑战和机遇。