Electrical stimulation via repeated biphasic conducting materials for peripheral nerve regeneration.

Improved materials for peripheral nerve repair are needed for the advancement of new surgical techniques in fields spanning from oncology to trauma. In this study, we developed bioresorbable materials capable of producing repeated electric field gradients spaced 600 µm apart to assess the impact on neuronal cell growth, and migration. Electrically conductive, biphasic composites comprised of poly (glycerol) sebacate acrylate (PGSA) alone, and doped with poly (pyrrole) (PPy), were prepared to create alternating segments with high and low electrically conductivity. Conductivity measurements demonstrated that 0.05% PPy added to PSA achieved an optimal value of 1.25 × 10-4 S/cm, for subsequent electrical stimulation. Tensile testing and degradation of PPy doped and undoped PGSA determined that 35-40% acrylation of PGSA matched nerve mechanical properties. Both fibroblast and neuronal cells thrived when cultured upon the composite. Biphasic PGSA/PPy sheets seeded with neuronal cells stimulated for with 3 V, 20 Hz demonstrated a 5x cell increase with 1 day of stimulation and up to a 10x cell increase with 3 days stimulation compared to non-stimulated composites. Tubular conduits composed of repeated high and low conductivity materials suitable for implantation in the rat sciatic nerve model for nerve repair were evaluated in vivo and were superior to silicone conduits. These results suggest that biphasic conducting conduits capable of maintaining mechanical properties without inducing compression injuries while generating repeated electric fields are a promising tool for acceleration of peripheral nerve repair to previously untreatable patients.

Structural and mechanical characterization of bioresorbable, elastomeric nanocomposites from poly(glycerol sebacate)/nanohydroxyapatite for tissue transport applications.

Poly(glycerol sebacate) (PGS)/nanohydroxyapatite (nHA) composites were assessed to develop new materials for closure via tissue transport for nonhealing defects (e.g., cleft palate and large skin wounds). The elastic shape memory polymer, PGS, was reinforced with nHA at 3 and 5% loading to increase the mechanical properties compared with the undoped PGS. Differential scanning calorimetry (DSC) was utilized to identify a glass transition temperature (Tg ) of -25°C. X-ray diffraction demonstrated a reduction in the amorphous nature of the material. The Fourier transform infrared photoacoustic spectral (FTIR-PAS) data showed decreased CO bonding and increased hydrogen bonding with increased nHA incorporation. Composites exhibited Young's moduli in the range of 0.25-0.5 MPa and tensile strength of 1.5-3 N. No significant difference in extension to break (∼50 mm) with addition of nHA was observed. The elastic modulus significantly increased for 5% PGS/nHA compared to 0 and 3% PGS/nHA and tensile strength significantly increased for 3% PGS/nHA compared to 0 and 5% PGS/nHA. Degradation of 5% nHA/PGS significantly increased during the second week compared to PGS 0 and 3% PGS/nHA. The accelerated degradation for 5% PGS/nHA coupled with decreased flexibility and tensile strength implies an interruption in crosslinking. By maintaining flexibility and extension while increasing tensile strength, the 3% PGS/nHA doped satisfied the force range desired for closure of soft tissue defects. Based on this work, PGS with 3% nHA shape memory polymers should serve as a good candidate for closure of nonhealing soft tissues. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1366-1373, 2016.

Development and characterization of elastic nanocomposites for craniofacial contraction osteogenesis.

Development of resorbable elastic composites as an alternative means to apply contractive forces for manipulating craniofacial bones is described herein. Composites made from the biodegradable elastomer, poly (1,8-octanediol co-citric acid) (POC), and hydroxyapatite (nHA) with a 200 nm diameter (0-20% loadings) were created to develop a material capable of applying continuous contractive forces. The composites were evaluated for variation in their mechanical properties, rate of degradation, and interaction of the hydroxyapatite nanoparticles with the polymer chains. First, an ex vivo porcine model of cleft palate was used to determine the rate of cleft closure with applied force. The closure rate was found to be 0.505 mm N(-1) . From this approximation, the ideal maximum load was calculated to be 19.82 N, and the elastic modulus calculated to be 1.98 MPa. The addition of nHA strengthens POC, but also reduces the degradation time by 45%, for 3% nHA loading, compared to POC without nHA. X-ray diffraction data indicates that the addition of nHA to amorphous POC results in the formation of a semicrystalline phase of the POC adjacent to the nHA crystals. Based on the data, we conclude that amongst the 0-20% nHA loadings, a 3% loading of nHA in POC may be an ideal material (1.21 MPa elastic modulus and 13.17 N maximum load) to induce contraction forces capable of facilitating osteogenesis and craniofacial bone repair.

Biocompatibility and remodeling potential of pure arterial elastin and collagen scaffolds.

Surgical therapy of cardiovascular disorders frequently requires replacement of diseased tissues with prosthetic devices or grafts. In typical tissue engineering approaches, scaffolds are utilized to serve as templates to support cell growth and remodeling. Decellularized vascular matrices have been previously investigated as scaffolds for tissue engineering. However, cell migration into these scaffolds was inadequate due to the very tight matrix organization specific to the aortic structure. To address this problem, we prepared two types of decellularized scaffolds from porcine vascular tissues. Pure elastin scaffolds and pure collagen scaffolds were prepared by selectively removing the collagen component or elastin, respectively. In the current study, we use a subdermal implantation model to demonstrate that arterial elastin and collagen scaffolds exhibit enhanced potential for repopulation by host cells in vivo. Notably, numerous new collagen fibers and bundles were found within the remodeled elastin scaffolds and new elastin fibers within collagen scaffolds, respectively, clearly indicating their ability to support de novo extracellular matrix synthesis. We also show that biological cues such as growth factors are required for efficient repopulation of elastin and collagen scaffolds. Finally, we bring evidence that these scaffolds can be endothelialized in vitro for thrombosis resistance and thus can serve as promising candidates for cardiovascular tissue engineering.