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.

A series of studies have reported a constant global rise in the incidence of type 1 diabetes. Epidemiological and immunological studies have demonstrated that environmental factors may influence the pathogenesis, leading to a cell-mediated pancreatic β-cell destruction associated with humoral immunity. The search for the triggering factor(s) has been going on for the past century, and yet they are still unknown. This review provides an overview of some of the most well-known theories found in the literature: hygiene, viral, vitamin D deficiency, breast milk and cow's milk hypotheses. Although the hygiene hypothesis appears to be the most promising, positive evidence from animal, human and epidemiological studies precludes us from completely discarding any of the other hypotheses. Moreover, due to contrasting evidence in the literature, a single factor is unlikely to cause an increase in the incidence of diabetes all over the world, which suggests that a multifactorial process might be involved. Although the immunological mechanisms are still unclear, there seems to be some overlap between the various hypotheses. It is thought that the emphasis should be shifted from a single to a multifactorial process and that perhaps the ‘balance shift’ model should be considered as a possible explanation for the rise in the incidence of type 1 diabetes.

Fat grafting is one of the most revolutionary surgical techniques of our century, which has changed the field of plastic surgery and regenerative medicine. Early reports of fat grafting date back to the late 19^th century, but the results were unsatisfactory due to minimal graft retention. It wasn’t until Sydney R. Coleman challenged the dogma and introduced a standardized approach to fat grafting after years of research and learning from experts across the world. The Coleman technique represents an evolutionary approach to fat grafting, with three main components: harvesting, refinement, and placement. The Coleman technique has been adopted and modified by surgeons around the world because it has allowed a reliable increase in fat graft survival through a standardized process. This article discusses the influencing factors and milestones that led to this world known technique, as well as Dr. Coleman’s current practices, pearls, pitfalls, and lessons learned over the years. The knowledge of the true potential and usefulness of fat is in its infancy, with its regenerative potential becoming increasingly recognized. Current and future research will likely prove that autologous fat has many clinical applications beyond its well-known aesthetic and reconstructive benefits, and extending beyond the regenerative realm.