Platelet lysate derived macroporous hydrogel loaded with adipose stem cells for spinal cord injury repair.

Spinal cord injury (SCI) can result in irreversible neurological deficits, such as limb paralysis and dysfunctions of urination and defecation. Currently, there remains a dearth of effective therapeutic strategies to fully reverse the detrimental consequences of SCI. Stem cell transplantation, particularly adipose-derived stem cells (ASCs) transplantation, shows great promise in treating SCI. However, the low survival rate of transplanted cells and limited neural differentiation impede its long-term clinical effectiveness. In this study, platelet lysate-rich plasma (PLP) was utilized as the primary matrix component. Through sodium alginate cross-linking, a platelet lysate-rich plasma hydrogel (PLPH) with a micron-scale macroporous structure was fabricated. By precisely modulating the component ratios, PLPH was engineered to possess a low Young's modulus (approximately 1000 Pa), which is comparable to that of spinal cord tissue, along with characteristics such as a low swelling ratio, high porosity, and slow degradation. In vitro, PLPH facilitated the proliferation of ASCs and offered neuroprotection under oxidative stress conditions. Moreover, it promoted axonal growth in neuronal cells. In a mouse model of spinal cord injury, PLPH-loaded ASCs induced M2 polarization of microglia/macrophages at the injury site by activating the signal transducer and activator of transcription 6 (STAT6) pathway, thereby suppressing the inflammatory response. Additionally, PLPH promoted the survival and neural differentiation of loaded ASCs in vivo, and also recruited neural progenitor cells, induced early differentiation of neurons and oligodendrocytes, inhibited glial scar formation, promoted axonal and myelin regeneration, and ultimately enhanced neurological functional recovery. As a hydrogel material derived from natural biological sources, PLPH holds great potential in providing novel alternatives for clinical stem cell transplantation therapies.