Biocompatibility and Characterization of a Peptide Amphiphile Hydrogel for Applications in Peripheral Nerve Regeneration

Abstract

Peripheral nerve injury is a debilitating condition for which new bioengineering solutions are needed. Autografting, the gold standard in treatment, involves sacrifice of a healthy nerve and results in loss of sensation or function at the donor site. One alternative solution to autografting is to use a nerve guide conduit designed to physically guide the nerve as it regenerates across the injury gap. Such conduits are effective for short gap injuries, but fail to surpass autografting in long gap injuries. One strategy to enhance regeneration inside conduits in long gap injuries is to fill the guide conduits with a hydrogel to mimic the native extracellular matrix found in peripheral nerves. In this work, a peptide amphiphile (PA)-based hydrogel was optimized for peripheral nerve repair. Hydrogels consisting of the PA C16GSH were compared with a commercially available collagen gel. Schwann cells, a cell type important in the peripheral nerve regenerative cascade, were able to spread, proliferate, and migrate better on C16GSH gels in vitro when compared with cells seeded on collagen gels. Moreover, C16GSH gels were implanted subcutaneously in a murine model and were found to be biocompatible, degrade over time, and support angiogenesis without causing inflammation or a foreign body immune response. Taken together, these results help optimize and instruct the development of a new synthetic hydrogel as a luminal filler for conduit-mediated peripheral nerve repair.

Self‐Healing Supramolecular Hydrogels for Tissue Engineering Applications

“…Upon inclusion of a MMP‐cleavable linker within the peptide sequence, enhanced viability, spreading, and migration of human mesenchymal stem cells was observed . This material lacks the ability to completely self‐heal, as the MMP‐cleavable linkers are permanently cut during cell invasion, however, PAs with repeated self‐healing abilities have also been explored for regeneration of nerves and angiogenesis …”

Self-assembling peptide-based building blocks in medical applications

“…Lastly, bioactive peptides for epitope-specific biological interactions can also be incorporated; for example, cell adhesion molecules are often incorporated to mimic native extracellular matrices (Figure 8). In recent years, the majority of in vivo applications using cylindrical PA-based scaffolds include regeneration for, bone [198], nerves [199–202], and reproductive organs [203]. …”

“…Regarding applications in the nervous system, recent attention has been focused on bioengineering nerve constructs for peripheral nerve injuries [199–202]. Li et al .…”

New insights into the roles of myofibroblasts and innervation during skin healing and innovative therapies to improve scar innervation

“…Due to the distinct role of different neuropeptides and NTs, the use of a cocktail would be interesting with delivery either by single administration or ideally by delayed delivery into the wound . Thus, different delivery systems are possible via topical application or using vehicles such as microspheres, hydrogel or gelatin . A recent study using a specific ECM to capture and deliver platelet‐derived growth factor into the wound could also be an interesting alternative as a carrier of neuropeptides and to concentrate their positive effects within the wound …”