Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid)

Abstract

We developed a microfibrous poly(L-lactic acid) (PLLA) nerve conduit with a three-layered structure to simultaneously enhance nerve regeneration and prevent adhesion of surrounding tissue. The inner layer was composed of PLLA microfiber containing 25% elastin-laminin mimetic protein (AG73-(VPGIG)30) that promotes neurite outgrowth. The thickest middle layer was constructed of pure PLLA microfibers that impart the large mechanical strength to the conduit. A 10% poly(ethylene glycol) was added to the outer layer to prevent the adhesion with the surrounding tissue. The AG73-(VPGIG)30 compositing of an elastin-like repetitive sequence (VPGIG)30 and a laminin-derived sequence (RKRLQVQLSIRT: AG73) was biosynthesized using Escherichia coli. The PLLA microfibrous conduits were fabricated using an electrospinning procedure. AG73-(VPGIG)30 was successfully mixed in the PLLA microfibers, and the PLLA/AG73-(VPGIG)30 microfibers were stable under physiological conditions. The PLLA/AG73-(VPGIG)30 microfibers enhanced adhesion and neurite outgrowth of PC12 cells. The electrospun microfibrous conduit with a three-layered structure was implanted for bridging a 2.0-cm gap in the tibial nerve of a rabbit. Two months after implantation, no adhesion of surrounding tissue was observed, and the action potential was slightly improved in the nerve conduit with the PLLA/AG73-(VPGIG)30 inner layer.

Evaluation of extracellular matrix mimetic laminin bioactive peptide and elastin‐like polypeptide

“…Furthermore, these bioactive peptides found their way into recombinantly expressed Escherichia coli as an alternative approach to sometimes harsh bioconjugation strategies. [17][18][19] Specifically, these bioactive peptides have been carefully engineered to be incorporated with biopolymers that act as scaffolds, which enhance the biophysiochemical properties or production of these small peptides.…”

Composite of Elastin-Based Matrix and Electrospun Poly(L-Lactic Acid) Fibers: A Potential Smart Drug Delivery System

“…To the best of our knowledge, there are only few examples of elastin-like based composites that have been developed till now (reviewed in Kakinoki et al, 2014 ; Yeo et al, 2015 ). Here, we describe an approach to obtain a new composite material based on deposition of elastin-like based on electrospun poly-L-lactic acid (PLLA-HELP).…”

Protein engineering and other bio-synthetic routes for bio-based materials: current uses and potential applications

“…Following their theme, most of the articles in the current Research Topic fit in the category of Using Biology as a Material . For example, several original research papers report the utilization of genetically-engineered proteins to obtain materials for various applications such as: tunable hydrogels (Tang and Olsen, 2014 ), hydrogels for mechanically active tissues (Li and Kiick, 2014 ), bacterial collagen for tissue engineering (An et al, 2014 ), and microfibers for nerve guide conduits (Kakinoki et al, 2014 ). Plant viruses (Pongkwan et al, 2014 ) and antimicrobial peptides (Rodriguez et al, 2014 ) are the starting bio-based materials to incorporate new functionalities by well-known chemical methods.…”