Peripheral nerve growth within a hydrogel microchannel scaffold supported by a kink-resistant conduit.

Nerve repair in several mm-long nerve gaps often requires an interventional technology. Microchannel scaffolds have proven effective for bridging nerve gaps and guiding axons in the peripheral nervous system (PNS). Nonetheless, fabricating microchannel scaffolds at this length scale remains a challenge and/or is time consuming and cumbersome. In this work, a simple computer-aided microdrilling technique was used to fabricate 10 mm-long agarose scaffolds consisting of 300 µm-microchannels and 85 µm-thick walls in less than an hour. The agarose scaffolds alone, however, did not exhibit adequate stiffness and integrity to withstand the mechanical stresses during implantation and suturing. To provide mechanical support and enable suturing, poly caprolactone (PCL) conduits were fabricated and agarose scaffolds were placed inside. A modified salt-leaching technique was developed to introduce interconnected porosity in PCL conduits to allow for tuning of the mechanical properties such as elastic modulus and strain to failure. It was shown that the PCL conduits were effective in stabilizing the agarose scaffolds in 10 mm-long sciatic nerve gaps of rats for at least 8 weeks. Robust axon ingress and Schwann cell penetration were observed within the microchannel scaffolds without using growth factors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3392-3399, 2017.

Characterizing the degradation of alginate hydrogel for use in multilumen scaffolds for spinal cord repair.

Alginate was studied as a degradable nerve guidance scaffold material in vitro and in vivo. In vitro degradation rates were determined using rheology to measure the change in shear modulus vs time. The shear modulus decreased from 155 kPa to 5 kPa within 2 days; however, alginate samples maintained their superficial geometry for over 28 days. The degradation behavior was supported by materials characterization data showing alginate consisted of high internal surface area (400 m2 /g), which likely facilitated the release of cross-linking cations resulting in the rapid decrease in shear modulus. To assess the degradation rate in vivo, multilumen scaffolds were fabricated using a fiber templating technique. The scaffolds were implanted in a 2-mm-long T3 full transection rodent spinal cord lesion model for 14 days. Although there was some evidence of axon guidance, in general, alginate scaffolds degraded before axons could grow over the 2-mm-long lesion. Enabling alginate-based scaffolds for nerve repair will likely require approaches to slow its degradation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 611-619, 2016.

Brain derived neurotrophic factor release from layer-by-layer coated agarose nerve guidance scaffolds.

Agarose nerve guidance scaffolds (NGS) seeded with cells expressing brain derived neurotrophic factor (BDNF) have demonstrated robust nerve regeneration in the rat central nervous system. The purpose of this work was to explore whether agarose NGS coated with hydrogen-bonded layer-by-layer (HLbL) could provide an acellular method of delivering prolonged and consistent dosages of active BDNF. Our results show that HLbL-coated agarose NGS could release BDNF over 10days in consistent dosages averaging 80.5±12.5(SD)ng/mL. Moreover, the BDNF released from HLbL was confirmed active by in vitro cell proliferation assays. To our knowledge, this is the first report demonstrating that HLbL assembled onto a hydrogel can provide consistent, prolonged release of active BDNF in clinically relevant dosages.