Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates.

Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line-derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 µm2) compared to autograft (4.62 ± 3.99 µm2) and PCL/Empty (4.52 ± 5.16 µm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

Administration of adipose-derived stem cells enhances vascularity, induces collagen deposition, and dermal adipogenesis in burn wounds.

Current treatment options for severe burn wounds are often insufficient in reconstructing skin and soft tissue defects. Adipose-derived stem cells (ASCs), a readily available source of multipotent stem cells, represent a promising therapy for the treatment of full-thickness burn wounds. Full-thickness burn wounds were created on the paraspinal region of athymic mice. A one-time, sub-eschar injection of 6.8×10(6) ASCs in PBS or PBS alone was administered at 24-h postoperatively. Time to healing was quantified using Image J analysis. At days 4, 7, 14, and 21, mice were sacrificed and tissues were excised for molecular and histological analysis. ASCs were able to survive in burn wounds as determined by the presence of PKH labeling and human PPARγ expression within the wounds. CD-31 staining demonstrated increased vascularity in ASC-treated wounds at POD 4 (p<0.05). Molecular studies showed enhanced adipogenesis, as well as type III and type I collagen deposition in the ASC treated group (p<0.05). An increase in the mRNA expression ratio of type III to type I collagen was also observed following ASC treatment (p<0.05). By enhancing vascularity, collagen deposition, and adipogenesis, ASCs show promise as an adjunctive therapy for the current treatment of full thickness burn wounds.