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M Borkenhagen

Publications and source records attributed to M Borkenhagen.

4 recordsLinked to original sources
PubMed1998

Three-dimensional extracellular matrix engineering in the nervous system.

Growing neurites are guided through their environment during development and regeneration via different cellular and extracellular matrix (ECM) molecular cues. To mimic cell-matrix interactions, a three-dimensional (3D) hydrogel-based ECM equivalent containing a covalently immobilized laminin oligopeptide sequence was designed to facilitate nerve regeneration. This study illustrates that the oligopeptide domain CDPGYIGSR covalently linked to an agarose gel as a bioartificial 3D substrate successfully supports neurite outgrowth from dorsal root ganglia (DRG) in vitro. The specificity of the neurite promoting activity was illustrated through the inhibition of neurite outgrowth from DRG in a CDPGYIGSR-derivatized gel in the presence of solubilized CDPGYIGSR peptide. Gels derivatized with CDPGYIGSK and CDPGRGSYI peptides stimulated a smaller increase of neurite outgrowth. In vivo experiments revealed the capability of a CDPGYIGSR-derivatized gel to enhance nerve regeneration in a transected rat dorsal root model compared to an underivatized gel, a CDPGRGSYI gel, and saline-filled nerve guidance channels. These data suggest the feasibility of a 3D hydrogel-based ECM equivalent capable of enhancing neurite outgrowth in vitro and in vivo.

Animals↗
PubMed1998

In vivo performance of a new biodegradable polyester urethane system used as a nerve guidance channel.

Biodegradable nerve guidance channels (NGCs) represent a promising alternative to current clinical nerve repair procedures. To be suitable as a NGC material, the polymer system should possess elastomeric properties and degrade at a defined rate without interfering with the regenerating environment. Polymers made of non-crystallizable blocks of poly[glycolide-co-(epsilon-caprolactone)]-diol and crystallizable blocks of poly[(R)-3-hydroxybutyric acid-co-(R)-3-hydroxyvaleric acid]-diol (PHB) can be modulated so as to respond to those criteria. Tubular structures were fabricated from three different types of materials containing either 41, 17 or 8 wt% PHB. Nerve regeneration through a 10 mm long NGC using a transected sciatic nerve model with an 8 mm gap was studied in rats at 4, 12 and 24 weeks. Out of 26 implanted NGCs, 23 contained regenerated tissue cables centrally located within the channel lumen and composed of numerous myelinated axons and Schwann cells. No significant difference in the degree of regeneration was observed between the various channel types. The inflammatory reaction associated with the polymer degradation had not interfered with the nerve regeneration process. Macrophages and giant cells surrounded polymer material remnants. A weight loss of 33, 74 and 88% for polymers containing 41, 17 and 8 wt% PHB was observed after 24 weeks by nuclear magnetic resonance (NMR) anaylsis, respectively. In all cases, the polymer fragments had a porous appearance with multiple surface cracks as evidenced by scanning electron microscopical analysis. Guidance channels made of 8 wt% PHB containing polymer displayed the highest degree of degradation at 24 weeks with only small polymer fragments remaining. The present study suggests that this new biodegradable elastomeric polymeric material holds promises for its utilization as nerve guidance channels.

Animals↗