Gregorio Nicole E, Zhang Fan, Suita Yusuke, Ang Lisa S, Prado Olivia, Fasuyi Arafat, Olson James M, Stevens Kelly R, DeForest Cole A
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Seattle Children's Research Institute, Seattle, WA 98101, USA.
Sci Adv. 2025 Aug 29;11(35):eadx3472. doi: 10.1126/sciadv.adx3472. Epub 2025 Aug 27.
Hydrogel biomaterials offer great promise for three-dimensional cell culture and therapeutic delivery. Despite many successes, challenges persist in that gels formed from natural proteins are only marginally tunable whereas those derived from synthetic polymers lack intrinsic bioinstructivity. Toward the creation of biomaterials with both excellent biocompatibility and customizability, recombinant protein-based hydrogels have emerged as molecularly defined and user-programmable platforms that mimic the proteinaceous nature of the extracellular matrix. Here, we introduce PhoCoil, a dynamically tunable recombinant hydrogel formed from a single protein component with unique multistimuli responsiveness. Physical cross-linking through coiled-coil interactions promotes rapid shear-thinning and self-healing behavior, rendering the gel injectable, whereas an included photodegradable motif affords on-demand network dissolution via visible light. PhoCoil gel photodegradation can be spatiotemporally and lithographically controlled in a dose-dependent manner, through complex tissue, and without harm to encapsulated cells. We anticipate that PhoCoil will further enable applications in tissue engineering and regenerative medicine.
水凝胶生物材料在三维细胞培养和治疗递送方面展现出巨大潜力。尽管已取得诸多成功,但仍存在挑战,天然蛋白质形成的凝胶仅有有限的可调性,而合成聚合物衍生的凝胶缺乏内在的生物指导性。为了创建具有优异生物相容性和可定制性的生物材料,基于重组蛋白的水凝胶已成为分子定义明确且用户可编程的平台,可模拟细胞外基质的蛋白质性质。在此,我们介绍PhoCoil,一种由单一蛋白质组分形成的动态可调重组水凝胶,具有独特的多刺激响应性。通过卷曲螺旋相互作用进行的物理交联促进了快速剪切变稀和自愈行为,使凝胶可注射,而包含的光可降解基序可通过可见光实现按需网络溶解。PhoCoil凝胶的光降解可以通过复杂组织以剂量依赖的方式进行时空和光刻控制,且不会对封装的细胞造成伤害。我们预计PhoCoil将进一步推动其在组织工程和再生医学中的应用。