Yifeng Zheng (Heidelberg, DE), Dr. Thomas Schackel (Heidelberg, DE), Maximilian Nuetzl (Regensburg, DE), Professor Rainer Müller (Regensburg, DE), Norbert Weidner (Heidelberg, DE), Radhika Puttagunta (Heidelberg, DE)
Abstract text (incl. figure legends and references)
Biomaterial engineering using alginate capillary hydrogels (ACHs) is a promising strategy to promote axonal regrowth following spinal cord injury (SCI), given its mechanical tunability, directed growth guidance, and permissive growth substrate. However, due to improper host-scaffold integration and fibroglia scar formation around the ACH, functional axonal regrowth beyond the lesion is marginal. Recent advances in neuronal mechanobiology have renewed interest in optimizing the mechanical properties of biomaterials to match the host tissue and reduce foreign body response to provide seamless integration. So far, the impact of biomaterial mechanics on the injured spinal cord has not been fully investigated. Here, we examine whether stiffness-adjusted ACH scaffolds benefit host integration and axonal growth potential. Following a rat cervical (C5) lateral hemisection SCI, polypeptide-modified ACH scaffolds with an elastic modulus ranging from 10kPa to 1kPa, approaching the stiffness of the adult rat spinal cord, were implanted into the lesion. Four weeks post-implantation, scaffolds with a stiffness approaching that of the spinal cord successfully minimized the host glia, immune, and chondroitin sulfate proteoglycan (CSPG) response around the scaffolds. Simultaneously, the softest scaffold maximized cell infiltration and angiogenesis within capillaries, leading to significant axonal regrowth into the scaffolds. Conversely, the softest scaffold resulted in capillary instability and the least rostral-caudal oriented axonal regrowth. Currently, we are examining the mechanics of implanted ACH scaffolds and the surrounding host tissue via atomic force microscopy. In summary, our findings suggest that stiffness plays a crucial role in scaffold integration with the spinal cord and its effect on axonal regrowth following SCI in vivo. Hence, optimizing the scaffold's mechanical properties could enhance the efficacy of host-scaffold intergration and neuroregenerative properties.