Photochemical sealing of a nerve wrap over the repair site isolates and optimizes the regenerating nerve microenvironment. To facilitate clinical adoption of the technology, we investigated photosealed autologous tissue in a rodent sciatic nerve transection and repair model. Rats underwent transection of the sciatic nerve with repair performed in three groups: standard microsurgical neurorrhaphy (SN) and photochemical sealing with a crosslinked human amnion (xHAM) or autologous vein. Functional recovery was assessed at four-week intervals using footprint analysis. Gastrocnemius muscle mass preservation, histology, and nerve histomorphometry were evaluated at 120 days. Nerves treated with a PTB-sealed autologous vein improved functional recovery at 120 days although the comparison between groups was not significantly different (SN: −58.4 +/− 10.9; XHAM: −57.9 +/− 8.7; Vein: −52.4 +/− 17.1). Good muscle mass preservation was observed in all groups, with no statistical differences between groups (SN: 69 +/− 7%; XHAM: 70 +/− 7%; Vein: 70 +/− 7%). Histomorphometry showed good axonal regeneration in all repair techniques. These results demonstrate that peripheral nerve repair using photosealed autologous veins produced regeneration at least equivalent to current gold-standard microsurgery. The use of autologous veins removes costs and foreign body concerns and would be readily available during surgery. This study illustrates a new repair method that could restore normal endoneurial homeostasis with minimal trauma following severe nerve injury.

Developing a functional tissue-engineered articular cartilage remains a challenge to improving clinical treatment of cartilage injury and joint-related degenerative disease. The dynamic self-regenerating cartilage (dSRC) approach presented here encourages autologous chondrocytes to generate their own matrix rather than imposing a matrix upon them. dSRC constructs were grown for 12 weeks under hypoxic conditions in reciprocating motion. Biochemical composition was evaluated, specifically water, collagen, and proteoglycan content. Speckle rHEologicAl micRoscopy (SHEAR) was utilized for spatially resolved evaluation of the shear modulus in engineered cartilage. Histological and immunohistochemical analyses of dSRC were also performed. The maturation of the dSRC matrix results in collagen and glycosaminoglycan (GAG) levels around 50% of those in native cartilage. SHEAR images demonstrate an increase in shear modulus of the matrix to ~20% that of native cartilage after 12 weeks. Histological support for excellent collagen and GAG production was evident, and immunohistochemistry showed a high preference for hyaline-like type II collagen in the neomatrix. A decrease in chondrocyte density occurred from an initial hypercellular matrix to that approaching native cartilage by 12 weeks. While this maturation of dSRC in vitro should not be construed as an absolute prediction of in vivo performance, these results are encouraging, representing a potential new cartilage repair and regeneration approach.

Peripheral nerve injuries affect 13–23 per 100,000 people annually in the U.S. and often result in motor and sensory deficits. Microsurgical suture repair (SR) is the standard treatment but is technically challenging and associated with complications. Photochemical tissue bonding (PTB), which uses light and a photoactivated dye to bond collagenous tissues, offers a promising alternative. We compared PTB with commercially available collagen membranes for SR and PTB using cryopreserved human amnion (HAM) in a rat sciatic nerve transection model. In total, 75 Lewis rats underwent nerve repair with one of five methods: SR, PTB-HAM, PTB with commercial collagenous membranes (human amnion monolayer (AML), human amnion–chorion–amnion trilayer (ATL), or swine intestinal submucosa (SIS)). Functional recovery was assessed with walking tracks and the Static Sciatic Index (SSI) at days 30, 60, 90, and 120; histological evaluations at days 30 and 120 examined inflammation, axon density, and fascicle structure. No significant differences in SSI scores were found between groups, though PTB-AML and PTB-SIS improved over time. Histology showed inflammation at day 30 that decreased by day 120. Histomorphometry revealed similar axon regeneration across groups. These results suggest that PTB with commercial membranes is a viable alternative to SR.