Long-term exploratory evaluation of an acellular biomimetic polyfascicular nerve guidance conduit for peripheral nerve repair in a rhesus macaque model.
This study provides preliminary evidence that an acellular biomimetic nerve guidance conduit may support nerve regeneration in a non-human primate model, but further research is needed to confirm its efficacy in humans.
Where it sits
this study against the rest of the ghrp-6 corpusSummary and findings
This study evaluated an acellular biomimetic multi-fascicle nerve guidance conduit (MFNGC) for peripheral nerve repair in a rhesus macaque model. The MFNGC was assessed over a 12-month period using a 15-mm median nerve defect model. Evidence of functional and histological nerve regeneration was observed.
Abstract
Peripheral nerve injury (PNI) affects millions worldwide, yet currently approved nerve guidance conduits (NGCs) have limited ability to recapitulate the native fascicular architecture that supports organized axonal regeneration. Here, we present an acellular biomimetic multi-fascicle NGC (MFNGC) constructed by integrating electrospun poly(L-lactide-co-ε-caprolactone) (PLCL) membranes with visible-light-crosslinked gelatin hydrogel guide structures, without cells or exogenous growth factors. The MFNGC incorporates three inner conduits mimicking perineurial fascicles enclosed within an epineurium-like outer conduit, approximating key architectural features of the native median nerve in rhesus macaques. In a 12-month exploratory follow-up study using a 15-mm median nerve defect model in three rhesus macaques (<i>Macaca mulatta</i>), the MFNGC showed evidence of functional and histological nerve regeneration, as assessed by compound muscle action potential (CMAP), hand dexterity using pellet clearance test, motor dysfunction scoring, thenar muscle preservation, and axonal remyelination. Nerves regenerated within the MFNGC exhibited organized multi-fascicular tissue formation resembling native nerve architecture, and the conduit showed substantial <i>in vivo</i> degradation, as indicated by a 94% reduction in PLCL molecular weight without obvious chronic inflammatory response at the 12-month endpoint. Although limited by the small number of NHP, this study provides exploratory preclinical evidence supporting further evaluation of an acellular polyfascicular NGC for peripheral nerve regeneration.
Background
Peripheral nerve injury (PNI) is a significant clinical challenge, affecting millions globally. Current nerve guidance conduits (NGCs) have limitations in mimicking the native architecture necessary for effective axonal regeneration. This study aims to explore a new acellular biomimetic multi-fascicle NGC designed to enhance nerve repair in a preclinical model.
Methods
The study utilized a 15-mm median nerve defect model in three rhesus macaques (<i>Macaca mulatta</i>). The MFNGC was constructed using electrospun poly(L-lactide-co-ε-caprolactone) (PLCL) membranes and gelatin hydrogel structures. The primary outcome measures included functional assessments such as CMAP and hand dexterity tests, with a follow-up duration of 12 months.
Results
At the 12-month endpoint, there was a 94% reduction in PLCL molecular weight, indicating significant degradation of the conduit. Functional assessments showed evidence of nerve regeneration, including improvements in CMAP and hand dexterity. Histological analysis revealed organized multi-fascicular tissue formation.
Interpretation
The findings suggest that the MFNGC may facilitate nerve regeneration, as evidenced by organized tissue formation and functional recovery. However, the effect size and clinical significance remain uncertain due to the small sample size and lack of human data. Further studies are necessary to validate these findings in larger populations.
Key findings
- 94% reduction in PLCL molecular weight at 12 months.
- Functional nerve regeneration assessed by compound muscle action potential (CMAP) and hand dexterity tests.
- Evidence of organized multi-fascicular tissue formation resembling native nerve architecture.
Limitations
- small n=3 rhesus macaques
- no human data available
- short follow-up period of 12 months
- no long-term durability data