Injectable hydrogels with tunable physiochemical and biological properties are potential tools for improving neural stem/progenitor cell (NSPC) transplantation to treat central nervous system (CNS) injury and disease. Here, we developed injectable diblock copolypeptide hydrogels (DCH) for NSPC transplantation that contain hydrophilic segments of modified l-methionine (Met). Multiple Met-based DCH were fabricated by post-polymerization modification of Met to various functional derivatives, and incorporation of different amino acid comonomers into hydrophilic segments. Met-based DCH assembled into self-healing hydrogels with concentration and composition dependent mechanical properties. Mechanical properties of non-ionic Met-sulfoxide formulations (DCH_MO) were stable across diverse aqueous media while cationic formulations showed salt ion dependent stiffness reduction. Murine NSPC survival in DCH_MO was equivalent to that of standard culture conditions, and sulfoxide functionality imparted cell non-fouling character. Within serum rich environments in vitro, DCH_MO was superior at preserving NSPC stemness and multipotency compared to cell adhesive materials. NSPC in DCH_MO injected into uninjured forebrain remained local and, after 4 weeks, exhibited an immature astroglial phenotype that integrated with host neural tissue and acted as cellular substrates that supported growth of host-derived axons. These findings demonstrate that Met-based DCH are suitable vehicles for further study of NSPC transplantation in CNS injury and disease models.

具有可调节的理化和生物学特性的可注射水凝胶是改善神经干/祖细胞（NSPC）移植以治疗中枢神经系统（CNS）损伤和疾病的潜在工具。在这里，我们开发了用于NSPC移植的可注射二嵌段共多肽水凝胶（DCH），其中包含修饰的1-甲硫氨酸（Met）的亲水链段。通过将Met聚合后修饰为各种功能衍生物，然后将不同的氨基酸共聚单体掺入亲水链段中，可以制备多个基于Met的DCH。基于Met的DCH组装成具有浓度和组成相关的机械性能的自修复水凝胶。非离子型Met亚砜配方（DCH _MO）在各种水性介质中均保持稳定，而阳离子配方则显示出盐离子依赖性的刚性降低。DCH _MO中的鼠NSPC存活率与标准培养条件相当，并且亚砜功能赋予细胞无污染特性。在体外富含血清的环境中，与细胞粘附材料相比，DCH _MO在保留NSPC干性和多能性方面表现优异。NSPC在DCH _MO中注射到未受伤的前脑中仍保持局部状态，并在4周后表现出不成熟的星形胶质表型，该表型与宿主神经组织整合在一起，并充当支持宿主衍生轴突生长的细胞基质。这些发现表明，基于Met的DCH是在中枢神经系统损伤和疾病模型中进一步研究NSPC移植的合适载体。