A study on tacrolimus combined with hyaluronic acid gel to inhibit scar proliferation at nerve anastomoses

Abstract Objective : To investigate the effect of additional application of hyaluronic acid (HA) gel containing tacrolimus (FK506) at the nerve anastomosis site after acute peripheral nerve injury treated with xenogeneic nerve transplantation on inhibiting the growth and formation of scar around the anastomosis. Methods : A total of 60 healthy male Sprague-Dawley (SD) rats weighing 250 g to 350 g were selected. Among them, 20 rats were used as nerve donors, and the remaining 40 rats were randomly divided into 4 groups. The groups were as follows: combination group (acellular xenogeneic nerve transplantation + application of HA gel containing FK506 at the anastomosis site), tacrolimus group (FK506 group, acellular xenogeneic nerve transplantation + application of FK506 at the anastomosis site), hyaluronic acid group (HA group, acellular xenogeneic nerve transplantation + application of HA at the anastomosis site), and control group (only acellular xenogeneic nerve transplantation was performed). Experimental procedures: 1. Donor nerve sampling; 2. Establishment of sciatic nerve defect and nerve transplantation model. 3. Sampling and detection: Tissue samples were collected 12 weeks after surgery, and analyzed by Peterson score, Masson staining, immunohistochemical analysis of type I and type III collagen, and counting of myelinated nerve fibers in the middle segment of the transplanted nerve. SPSS 23.0 statistical software was used for data processing and analysis. This study has been approved by the Animal Experimental Ethics Committee of Mudanjiang Medical University (Approval No.202009015). Confirming that all experiments were performed in accordance with relevant guidelines and regulations. Results :The results of Peterson score, Masson staining, immunohistochemical analysis of type I and type III collagen, and counting of myelinated nerve fibers in the middle segment of the transplanted nerve showed that: 1. The degree of adhesion between the nerve anastomosis and surrounding tissue was lighter in the combination group, FK506 group and HA group, all of which were better than that in the control group, and the differences were statistically significant (P < 0.05). 2. The amount of scar formation was the least in the combination group, intermediate in the FK506 group and HA group, and the largest in the control group. 3. The number of myelinated nerve fibers in the middle segment of the transplanted nerve in the combination group was higher than that in the other three groups (FK506 group, HA group, control group), and the difference between the combination group and the control group was highly statistically significant (P < 0.01). Conclusion :After acellular xenogeneic nerve transplantation, the effect of applying HA gel containing FK506 at the anastomosis site on inhibiting scar formation is better than that of applying FK506 alone or HA gel alone. HA gel containing FK506 can inhibit scar growth at the nerve anastomosis site and promote nerve regeneration.