Bench‐to‐Bedside Lessons Learned: Commercialization of an Acellular Nerve Graft

Abstract

Peripheral nerve injury can result in debilitating outcomes including loss of function and neuropathic pain. Although nerve repair research and therapeutic development are widely studied, translation of these ideas into clinical interventions has not occurred at the same rate. At the turn of this century, approaches to peripheral nerve repair have included microsurgical techniques, hollow conduits, and autologous nerve grafts. These methods provide satisfactory results; however, they possess numerous limitations that can prevent effective surgical treatment. Commercialization of Avance, a processed nerve allograft, sought to address limitations of earlier approaches by providing an off‐the‐shelf alternative to hollow conduits while maintaining many proregenerative properties of autologous grafts. Since its launch in 2007, Avance has changed the landscape of the nerve repair market and is used to treat tens of thousands of patients. Although Avance has become an important addition to surgeon and patient clinical options, the product's journey from bench to bedside took over 20 years with many research and commercialization challenges. This article reviews the events that have brought a processed nerve allograft from the laboratory bench to the patient bedside. Additionally, this review provides a perspective on lessons and considerations that can assist in translation of future medical products.

Effects of Chemical and Radiation Sterilisation on the Biological and Biomechanical Properties of Decellularised Porcine Peripheral Nerves

“…Currently, two decellularised human nerve grafts have undergone multicentre clinical evaluations; a non-commercial nerve graft for sensory nerve defects in China ( He et al, 2015 ) and the commercial Avance ® nerve graft from Axogen in the United States ( Kasper et al, 2020 ; Safa et al, 2020 ). Both are sterilised with 25 kGy gamma radiation; however, it is unclear why this method was selected, and limited data are available regarding the effects of the sterilisation process in isolation on the properties of the decellularised nerve tissue.…”

“…Both are sterilised with 25 kGy gamma radiation; however, it is unclear why this method was selected, and limited data are available regarding the effects of the sterilisation process in isolation on the properties of the decellularised nerve tissue. The results of initial trials indicated that both grafts were safe, did not elicit an adverse host immune response, and revealed that (at least partial) functional restoration could be achieved in short to moderate length (0.5–5 cm) defects ( He et al, 2015 ; Kasper et al, 2020 ; Safa et al, 2020 ). These initial data suggest that sterilisation with ionising radiation does not impair functional properties of decellularised nerves.…”

Nerve Guidance Conduits with Hierarchical Anisotropic Architecture for Peripheral Nerve Regeneration

“…[ 14–16 ] Multiple physical cues were also introduced into same nerve guidance graft systems to achieve improved outcomes and functional recovery. [ 17–19 ] Although recent studies using some of these approaches have revealed significant improvements in axonal regeneration and peripheral nerve repair, [ 3,13,20 ] challenges remain to optimize these physical factors.…”

Electroresponsive Silk-Based Biohybrid Composites for Electrochemically Controlled Growth Factor Delivery

“…Peripheral nerve axons can spontaneously regenerate to a certain extent after injury, but the probability of recovery decreases as the level of injury increases. Current therapeutic procedures are surgical, employing biomaterials to bridge nerve defects with varying degrees of success [24][25][26]. To enhance the probability of successful outcomes, the use of pharmacological agents and biomolecules, such as microRNAs or growth factors to promote nerve regeneration have gained attention over the last few years [27][28][29].…”