Premium
Keratin Biomaterials Activate Schwann Cells via Integrin‐Mediated Signaling and Promote Regeneration of Large Peripheral Nerve Defects in a Rabbit Model
Author(s) -
Sierpinski Paulina,
Apel Peter J,
Tawfik Bernard,
Smith Tom,
Koman L. Andrew,
Atala Anthony,
Van Dyke Mark
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.834.7
Subject(s) - keratin , regeneration (biology) , intermediate filament , chemistry , schwann cell , microbiology and biotechnology , integrin , alpha (finance) , peripheral nerve , cytoskeleton , anatomy , cell , biology , pathology , biochemistry , medicine , surgery , construct validity , patient satisfaction
Previous work in our lab has shown that alpha and gamma keratins can be extracted from human hair and processed into a hydrogel that promotes rapid regeneration of peripheral nerves in a mouse model. We have shown that this regeneration is partly due to activation of Schwann cells but the mechanism by which this happens is not known. Our aim in this study was to (1) evaluate the primary AA structure of known HHKs, (2) devise fractionation schemes that allow separation based on structural criteria, (3) investigate the effect that structural characteristics had on SC activity at a mechanistic level, and (4) assess the ability of a keratin gel to regenerate large peripheral nerve defects. Here we show that keratins can be effectively separated based on structural criteria, and that these structural characteristics have an effect on the receptor mediated‐signaling of Schwann cells. Cells grown on alpha, gamma and basic gamma keratin substrates had a 16‐18 fold upregulation in integrin αV over uncoated dishes. The acidic alpha fraction showed a 2.4‐fold increase in the pMAPK to MAPK ratio compared to the basic alpha fraction. Furthermore, we show that a keratin gel composed of alpha and gamma keratins promotes regeneration across a critical sized defect in a rabbit model. At 3 months, keratin treated nerves had significantly better conduction delay (4.5% vs. 21%) and improved CMAP (51% vs. 36%) over empty conduit controls.