(275i) Advancing Peripheral Nerve Regeneration through Surface Modification: Investigating the Impact of Layer-By-Layer ECM Coatings on Schwann Cell Response

Peripheral nerve injuries (PNIs) often require surgical intervention for repair, with autografts serving as the primary method for nerve regeneration. However, the use of autografts frequently leads to complications such infections, scarring, and the loss or decrease of donor site mobility. Additionally, patients undergoing autograft procedures may face the trouble of multiple surgeries. To mitigate these challenges associated with autografts, Nerve Guide Conduits (NGCs) have emerged as a promising alternative. Nevertheless, their efficacy is curtailed by limitations such as the deficiency of essential extracellular matrix (ECM) constituents inherent in autografts. For this reason, NGCs are used especially for managing smaller lesions. To address these challenges and enhance the regenerative capacity of NGCs, multifaceted strategies integrating tissue engineering principles and advanced surface modification techniques are being explored. Among these, layer-by-layer (LbL) assemblies stands out as a versatile approach for engineering biomimetic coatings on NGC surfaces. In particular, the combination of natural polymers such as Collagen (COL) and Heparin (HEP) via LbL techniques offers a suggesting avenue for enhancing NGC functionality and promoting nerve regeneration.

This comprehensive study encompasses three interconnected investigations aimed at elucidating the efficacy and potential of (HEP/COL) coatings on NGC surfaces in promoting nerve repair bioactivity of human Schwann cells (hSCs). Initially, the evaluation of 6 bilayers of (HEP/COL) coatings on NGC surfaces and their impact on the cell proliferation was carried out. An examination of the stability and degradation kinetics of (HEP/COL) coatings over time was also undertaken to assess their long-term performance in physiological conditions. And finally, the research extended its scope to evaluate the applicability of (HEP/COL) coatings onto commercial collagen-based NGCs.

In summary, we performed in vitro cell culture assays, comparing NGCs and Tissue culture plastic (TCP) both coated with (HEP/COL)₆ to uncoated controls, with and without the supplementation of Nerve Growth Factor (NGF). Results revealed enhanced cell proliferation, adhesion, and migration on (HEP/COL)₆ surfaces, attributed to the bioactive properties of the coatings and the presence of growth factors. Additionally, systematic characterization using techniques such as IR Variable Angle Spectroscopic Ellipsometry (IR-VASE) elucidated the robustness and sustained functionality of (HEP/COL)₆ coatings under simulated physiological conditions, crucial for their translational potential. This complete approach, combining in vitro cell culture assays and morphological analyses, demonstrated significant improvements in human Schwann cell viability, adhesion, and migration on (HEP/COL)₆, emphasizing the translational potential of this surface modification strategy.

Multifaceted strategies employed in advancing peripheral nerve regeneration, with a particular emphasis on the role of (HEP/COL)₆ on different surfaces provide valuable insights into the underlying mechanisms governing nerve regeneration and lays the groundwork for the development of next-generation NGCs with enhanced regenerative capacities through the integration of tissue engineering principles and advanced surface modification. This research represents a significant step forward in addressing the clinical challenges associated with peripheral nerve injuries.