Figure 3. Biomaterial-facilitated stem cell-based regenerative therapies for central nervous system applications.

(A) (A1 and A2) SMART spheroids were developed to improve cell-cell and cell-matrix interactions and achieve controlled drug release to enhance in vivo neuronal differentiation of transplanted stem cells, thereby leading to functional recovery in models of SCI. (A3) Injection of SMART neurospheres (spheroids assembled from NSCs) achieved long-term stem cell survival and neuronal differentiation along with reduced glial scar and functional recovery 1 month postinjection. Data are presented as means ± SEM, *p < 0.05 and **p < 0.01. (A4) Treatment with SMART neurospheres resulted in faster recovery rates at 1 month based on the Basso mouse scale (BMS) scoring. Data are presented as means ± SEM, *p < 0.05 (Rathnam et al., 2021).

(B) (B1 and B2) SHIELD, an injectable shear-thinning hydrogel, was designed to improve cell survival and engraftment after transplantation by incorporating celladhesive ligands and employing self-healing and thixotropic characteristics. (B3) immunostaining quantification of the lesion and perilesion regions in spinal cord sections revealed a significant reduction of the pan-macrophage marker ED1 in animals treated with Schwann cells (SCs) in SHIELD compared with injury only controls, whereas no significant differences were observed between the groups for Iba1, microglia marker, or Tomato lectin, vasculature marker. Data are presented as means ± SEM, *p < 0.05. (B4) Forelimb coordination significantly increased in SHIELD-delivered SCs-treated animals after 4 weeks as measured by a decrease in the percentage of missed steps with the horizontal ladder walk test. Data are presented as means ± SEM, *p < 0.05 and $p = 0.970 comparison between before injury and 4-week SCs in SHIELD (Marquardt et al., 2020). Figures reproduced with permission.