# Self‐Assembling Peptide Hydrogels Support Stromal Vascular Fraction Viability to Promote In Vivo Nerve Regeneration

## TL;DR

Injectable peptide gels help deliver cells that improve nerve repair in rats, matching the effectiveness of traditional grafts.

## Contribution

A self-assembling peptide hydrogel is shown to enhance stromal vascular fraction cell viability and promote nerve regeneration comparable to autografts.

## Key findings

- SVF delivered in optimized SAPH improved motor and sensory recovery in rat nerve defects.
- SAPH-supported SVF outperformed collagen controls and SAPH without SVF in nerve regeneration.
- qPCR suggests SAPH-delivered SVF has increased longevity compared to collagen-delivered SVF.

## Abstract

Autograft, the gold standard in nerve reconstruction, outperforms the alternatives of acellular allograft/nerve conduits likely due to the transplanted Schwann cell population within. The stromal vascular fraction (SVF) is a heterogenous cell isolate, that may improve nerve regeneration outcomes when transplanted at the site of a nerve defect. Self‐Assembling Peptide hydrogels (SAPH) are synthetic materials derived from short chains of biological amino acids. They are safe, injectable hydrogels whose charge and mechanical properties are easily tuned. Our hypothesis is that SVF, when transplanted within an SAPH, tailored toward nerve regeneration and SVF viability, will improve outcomes of nerve regeneration. In vitro modelling is used to select SAPH that support the viable 3D culture of SVF and outgrowth from neuronal explants. In vivo experimentation with a 10 mm rat sciatic nerve defect demonstrated that SVF, when delivered within a conduit, in a positively charged, mechanically optimized SAPH, significantly improved functional motor and sensory recovery compared to collagen controls and SAPH without SVF and is at least as good as autograft. Using male SVF, qPCR identification of Y chromosomal DNA suggested that SVF transplanted in SAPH has increased longevity when compared to SVF transplanted in collagen gel.

Stromal vascular fraction (SVF) may enhance nerve repair, especially when delivered in a self‐assembling peptide hydrogel (SAPH). In vitro, softer SAPH increased neuronal explant outgrowth and supported greater SVF viability and proliferation. In a rat sciatic defect, SVF in an optimized SAPH produced motor and sensory recovery equivalent to autograft and superior to SVF‐free controls (collagen & SAPH), with qPCR suggesting incorporation of SAPH‐delivered SVF, but not collagen‐delivered SAPH into the regenerated nerve.