Photo-crosslinked anhydride-modified polyester and -ethers for pH-sensitive drug release.

Photo-crosslinkable polymers have a great potential for the delivery of sensitive drugs. They allow preparation of drug releasing devices by photo-crosslinking, thus avoiding high processing temperatures. In this study, the hydrolysis behavior and drug release of three different photo-crosslinkable poly(ether anhydride)s and one poly(ester anhydride) were investigated. Three-arm poly(ethylene glycol) or polycaprolactone was reacted with succinic anhydride to obtain carboxylated macromers, and further functionalized with methacrylic anhydride to form methacrylated marcromers with anhydride linkages. The synthetized macromers were used to prepare photo-crosslinked matrices with different hydrolytic degradation times for active agent release purposes. The hydrolysis was clearly pH-sensitive: polymer networks degraded slowly in acidic conditions, and degradation rate increased as the pH shifted towards basic conditions. Drug release was studied with two water-soluble model drugs lidocaine (234 mol/g) and vitamin B12 (1355 g/mol). Vitamin B12 was released mainly due to polymer network degradation, whereas smaller molecule lidocaine was released also through diffusion and swelling of polymer network. Only a small amount of vitamin B12 was released in acidic conditions (pH 1.3 and pH 2.1). These polymers have potential in colon targeted drug delivery as the polymer could protect sensitive drugs from acidic conditions in the stomach, and the drug would be released as the conditions change closer to neutral pH in the intestine.

Biomimetic Photocurable Three-Dimensional Printed Nerve Guidance Channels with Aligned Cryomatrix Lumen for Peripheral Nerve Regeneration.

Repair and regeneration of critically injured peripheral nerves is one of the most challenging reconstructive surgeries. Currently available and FDA approved nerve guidance channels (NGCs) are suitable for small gap injuries, and their biological performance is inferior to that of autografts. Development of biomimetic NGCs with clinically relevant geometrical and biological characteristics such as topographical, biochemical, and haptotactic cues could offer better regeneration of the long-gap complex nerve injuries. Here, in this study, we present the development and preclinical analysis of three-dimensional (3D) printed aligned cryomatrix-filled NGCs along with nerve growth factor (NGF) (aCG + NGF) for peripheral nerve regeneration. We demonstrated the application of these aCG + NGF NGCs in the enhanced and successful regeneration of a critically injured rat sciatic nerve in comparison to random cryogel-filled NGCs, multichannel and clinically preferred hollow conduits, and the gold standard autografts. Our results indicated similar effect of the aCG + NGF NGCs viz-a-viz that of the autografts, and they not only enhanced the overall regenerated nerve physiology but could also mimic the cellular aspects of regeneration. This study emphasizes the paradigm that these biomimetic 3D printed NGCs will lead to a better functional regenerative outcome under clinical settings.