Objective . Spinal cord injury (SCI) affects a quarter million individuals in the United States, and there is currently no clinical treatment. Both fresh and acellular peripheral nerve grafts can induce spinal axon regeneration and support functional recovery in experimental injury models. Nonetheless, a scaffold that can be injected into a spinal contusion would be far less invasive to apply. We aimed to develop the first injectable acellular nerve graft for promoting repair after contusion SCI. Approach . We report a method to enzymatically solubilize optimized acellular (OA) nerve—a decellularized peripheral nerve graft developed in our laboratory and currently used clinically—to obtain an injectable solution that undergoes thermal gelation under physiological conditions. We quantified multiple physical and compositional properties of this novel material as well as tested its efficacy at acute and chronic time points following cervical contusion SCI. Main Results . This injectable optimized acellular (iOA) nerve graft retains native chemical cues such as collagens and glycosaminoglycans. By varying hydrogel concentration, the rheological properties and compressive modulus of iOA were similar to that previous reported for rat central nervous tissue. iOA solution was compatible with rat Schwann cells in culture, and hydrogel injection into a rat cervical contusion model significantly reduced the ratio of M1:M2 macrophages after one week, favoring regenerative phenotypes ( p < 0.05). Furthermore, while iOA treatment did not affect locomotor or respiratory recovery over an eight week period, the percentage of axonal coverage increased at the distal tissue interface ( p < 0.05), suggesting enhanced axonal extension within this region. Significance . Our data indicate that this novel injectable form of acellular nerve grafts is amenable for use after contusion SCI and may bolster a simultaneous therapy by acutely modulating the inflammatory milieu and supporting axonal growth.

We report biodegradable electroactive polymer (EAP)-based materials and their application as drug delivery devices. Copolymers composed of oligoaniline-based electroactive blocks linked to either polyethylene glycol or polycaprolactone blocks via ester bonds were synthesized in three steps from commercially available starting materials and isolated without the need for column chromatography. The physicochemical and electrochemical properties of the polymers were characterized with a variety of techniques. The ability of the polymers to deliver the anti-inflammatory drug dexamethasone phosphate on the application of electrochemical stimuli was studied spectroscopically. Films of the polymers were shown to be degradable and cell adhesive in vitro. Such EAP-based materials have prospects for integration in implantable fully biodegradable/bioerodible EAP-based drug delivery devices that are capable of controlling the chronopharmacology of drugs for future clinical application.

In situ crosslinking hydrogels are attractive for application as injectable hydrogel-based tissue scaffolds that adapt to fill patient-specific cavities. Oxime click chemistry was used to crosslink hydrogels that were biodegradable, soft and supportive of cell adhesion. Linear poly(ethylene glycol)s (PEGs, Mn 2 or 4 kDa) terminated at both ends with aminooxy moieties and hyaluronic acid (HA, Mn 2 MDa) derivatives displaying aldehydes were non-toxic towards primary Schwann cells. The PEG and HA derivatives form oxime crosslinked hydrogels with mechanical and swelling properties that were tunable based on the composition of the hydrogels to values analogous to soft tissues such as those found in the central or peripheral nervous system. Gels incorporating collagen-1 supported the adhesion of human mesenchymal stem cells. Such chemistry has the potential to generate clinically relevant injectable hydrogels for minimally invasive personalized medical procedures in the central or peripheral nervous systems.