Zhang He, Wang Jiangning, Wei Jiaona, Fu Xueqi, Ma Junfeng, Chen Jing
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
College of Plant Science, Jilin University, Changchun 130062, China.
Gels. 2025 Jul 26;11(8):579. doi: 10.3390/gels11080579.
Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed through a hierarchical crosslinking strategy, these hydrogels integrate reversible physical interactions with covalent crosslinking approaches, collectively endowing the system with mechanical strength, environmental responsiveness, and controlled degradation behavior. Critically, molecular engineering strategies serve as the cornerstone for functional precision: domain-directed self-assembly exploits coiled-coil or β-sheet motifs to orchestrate hierarchical organization, while modular fusion of bioactive motifs through genetic encoding or site-specific conjugation enables dynamic control over cellular interactions and therapeutic release. Such engineered designs underpin advanced applications, including immunomodulatory scaffolds for diabetic wound regeneration, tumor-microenvironment-responsive drug depots, and shear-thinning bioinks for vascularized bioprinting, by synergizing material properties with biological cues. By uniting synthetic biology with materials science, recombinant hydrogels deliver unprecedented flexibility in tuning physical and biological properties. This review synthesizes emerging crosslinking paradigms and molecular strategies, offering a framework for engineering next-generation, adaptive biomaterials poised to address complex challenges in regenerative medicine and beyond.
重组蛋白水凝胶已成为具有变革性的生物材料,通过利用基因工程骨架,如弹性蛋白样多肽、丝素蛋白(SF)和类 resilin 多肽,克服了传统合成系统的生物惰性和不可预测的降解,以复制细胞外基质(ECM)动态并实现可编程功能。这些水凝胶通过分层交联策略构建,将可逆的物理相互作用与共价交联方法相结合,共同赋予系统机械强度、环境响应性和可控的降解行为。至关重要的是,分子工程策略是功能精确性的基石:结构域定向自组装利用卷曲螺旋或β折叠基序来编排分层组织,而通过基因编码或位点特异性共轭对生物活性基序进行模块化融合能够动态控制细胞相互作用和治疗性释放。通过将材料特性与生物学线索协同作用,这种工程设计支撑了先进的应用,包括用于糖尿病伤口再生的免疫调节支架、肿瘤微环境响应性药物库以及用于血管化生物打印的剪切变稀生物墨水。通过将合成生物学与材料科学相结合,重组水凝胶在调节物理和生物学特性方面提供了前所未有的灵活性。本综述综合了新兴的交联模式和分子策略,为设计下一代适应性生物材料提供了一个框架,有望应对再生医学及其他领域的复杂挑战。
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