Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, Maastricht, 6200 MD, The Netherlands.
Advanced Functional Polymers Group, Department of Chemistry, Institute for Materials Research (IMO), Hasselt University, Martelarenlaan 42, Hasselt, 3500, Belgium.
Adv Mater. 2023 Sep;35(35):e2301242. doi: 10.1002/adma.202301242. Epub 2023 Jul 30.
Synthetic hydrogels often lack the load-bearing capacity and mechanical properties of native biopolymers found in tissue, such as cartilage. In natural tissues, toughness is often imparted via the combination of fibrous noncovalent self-assembly with key covalent bond formation. This controlled combination of supramolecular and covalent interactions remains difficult to engineer, yet can provide a clear strategy for advanced biomaterials. Here, a synthetic supramolecular/covalent strategy is investigated for creating a tough hydrogel that embodies the hierarchical fibrous architecture of the extracellular matrix (ECM). A benzene-1,3,5-tricarboxamide (BTA) hydrogelator is developed with synthetically addressable norbornene handles that self-assembles to form a and viscoelastic hydrogel. Inspired by collagen's covalent cross-linking of fibrils, the mechanical properties are reinforced by covalent intra- and interfiber cross-links. At over 90% water, the hydrogels withstand up to 550% tensile strain, 90% compressive strain, and dissipated energy with recoverable hysteresis. The hydrogels are shear-thinning, can be 3D bioprinted with good shape fidelity, and can be toughened via covalent cross-linking. These materials enable the bioprinting of human mesenchymal stromal cell (hMSC) spheroids and subsequent differentiation into chondrogenic tissue. Collectively, these findings highlight the power of covalent reinforcement of supramolecular fibers, offering a strategy for the bottom-up design of dynamic, yet tough, hydrogels and bioinks.
合成水凝胶通常缺乏组织中天然生物聚合物（如软骨）的承载能力和机械性能。在天然组织中，韧性通常通过纤维型非共价自组装与关键共价键形成的结合来赋予。这种超分子和共价相互作用的受控组合仍然难以设计，但可为先进的生物材料提供明确的策略。在这里，研究了一种合成的超分子/共价策略，以创建一种坚韧的水凝胶，该水凝胶体现了细胞外基质（ECM）的分层纤维状结构。开发了一种苯-1,3,5-三羧酸酰胺（BTA）水凝胶剂，具有可合成寻址的降冰片烯手柄，可自组装形成和粘弹性水凝胶。受胶原蛋白对原纤维的共价交联的启发，通过纤维内和纤维间的共价交联来增强机械性能。在超过 90%的水含量下，水凝胶可承受高达 550%的拉伸应变，90%的压缩应变，并以可恢复的滞后性耗散能量。水凝胶具有剪切稀化性，可以很好地保真度 3D 生物打印，并且可以通过共价交联进行增韧。这些材料使人类间充质基质细胞（hMSC）球体的生物打印成为可能，并随后分化为软骨组织。总的来说，这些发现突出了共价增强超分子纤维的力量，为动态但坚韧的水凝胶和生物墨水的自下而上设计提供了一种策略。
