Human Adipose Tissue Lysate‐Based Hydrogel for Lasting Immunomodulation to Effectively Improve Spinal Cord Injury Repair

Abstract The long‐term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue‐derived extracellular matrix hydrogel shows effective anti‐inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti‐inflammation function of the adipose tissue‐derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti‐inflammatory and nerve regeneration‐related proteins. Thereby, human adipose tissue lysate‐based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long‐term recruit and induce anti‐inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro‐inflammatory M1 macrophages regardless of human or mouse‐originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH‐induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 10 5 /100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.