Application of Adipose Stem Cells in 3D Nerve Guidance Conduit Prevents Muscle Atrophy and Improves Distal Muscle Compliance in a Peripheral Nerve Regeneration Model

Abstract

Background: Peripheral nerve injuries (PNIs) represent a significant clinical problem, and standard approaches to nerve repair have limitations. Recent breakthroughs in 3D printing and stem cell technologies offer a promising solution for nerve regeneration. The main purpose of this study was to examine the biomechanical characteristics in muscle tissue distal to a nerve defect in a murine model of peripheral nerve regeneration from physiological stress to failure. Methods: In this experimental study, we enrolled 18 Wistar rats in which we created a 10 mm sciatic nerve defect. Furthermore, we divided them into three groups as follows: in Group 1, we used 3D nerve guidance conduits (NGCs) and adipose stem cells (ASCs) in seven rats; in Group 2, we used only 3D NGCs for seven rats; and in Group 3, we created only the defect in four rats. We monitored the degree of atrophy at 4, 8, and 12 weeks by measuring the diameter of the tibialis anterior (TA) muscle. At the end of 12 weeks, we took the TA muscle and analyzed it uniaxially at 10% stretch until failure. Results: In the group of animals with 3D NGCs and ASCs, we recorded the lowest degree of atrophy at 4 weeks, 8 weeks, and 12 weeks after nerve reconstruction. At 10% stretch, the control group had the highest Cauchy stress values compared to the 3D NGC group (0.164 MPa vs. 0.141 MPa, p = 0.007) and the 3D NGC + ASC group (0.164 MPa vs. 0.123 MPa, p = 0.007). In addition, we found that the control group (1.763 MPa) had the highest TA muscle stiffness, followed by the 3D NGC group (1.412 MPa), with the best muscle elasticity showing in the group in which we used 3D NGC + ASC (1.147 MPa). At failure, TA muscle samples from the 3D NGC + ASC group demonstrated better compliance and a higher degree of elasticity compared to the other two groups (p = 0.002 and p = 0.008). Conclusions: Our study demonstrates that the combination of 3D NGC and ASC increases the process of nerve regeneration and significantly improves the compliance and mechanical characteristics of muscle tissue distal to the injury site in a PNI murine model.

Keywords

• peripheral nerve injuries
• peripheral nerve regeneration
• 3D nerve guidance conduit
• uniaxial
• mechanical characteristics
• stiffness