Regeneration of Subcutaneous Cartilage in a Swine Model Using Autologous Auricular Chondrocytes and Electrospun Nanofiber Membranes Under Conditions of Varying Gelatin/PCL Ratios.

Rui Zheng,Bingcheng Yi,Jixin Xue,Xiaoyun Wang,Hui Xu,Lin Yao,Guangdong Zhou,Zhengyu Shen,Yu Liu,Jie Chen,Mengjie Hou,Ruhong Zhang,Gaoyang Wu

doi:10.3389/fbioe.2021.752677

Abstract

The scarcity of ideal biocompatible scaffolds makes the regeneration of cartilage in the subcutaneous environment of large animals difficult. We have previously reported the successful regeneration of good-quality cartilage in a nude mouse model using the electrospun gelatin/polycaprolactone (GT/PCL) nanofiber membranes. The GT/PCL ratios were varied to generate different sets of membranes to conduct the experiments. However, it is unknown whether these GT/PCL membranes can support the process of cartilage regeneration in an immunocompetent large animal model. We seeded swine auricular chondrocytes onto different GT/PCL nanofiber membranes (GT:PCL = 30:70, 50:50, and 70:30) under the sandwich cell-seeding mode. Prior to subcutaneously implanting the samples into an autologous host, they were cultured in vitro over a period of 2 weeks. The results revealed that the nanofiber membranes with different GT/PCL ratios could support the process of subcutaneous cartilage regeneration in an autologous swine model. The maximum extent of homogeneity in the cartilage tissues was achieved when the G5P5 (GT: PC = 50: 50) group was used for the regeneration of cartilage. The formed homogeneous cartilage tissues were characterized by the maximum cartilage formation ratio. The extents of the ingrowth of the fibrous tissues realized and the extents of infiltration of inflammatory cells achieved were found to be the minimum in this case. Quantitative analyses were conducted to determine the wet weight, cartilage-specific extracellular matrix content, and Young’s modulus. The results indicated that the optimal extent of cartilage formation was observed in the G5P5 group. These results indicated that the GT/PCL nanofiber membranes could serve as a potential scaffold for supporting subcutaneous cartilage regeneration under clinical settings. An optimum GT/PCL ratio can promote cartilage formation.

Highlights

Cartilage defects in the subcutaneous environment due to congenital disease, cancer removal, or trauma are very common in plastic and reconstructive surgery (Wiggenhauser et al, 2017)
The results revealed that the GT/PCL nanofiber membranes (GT)/PCL membranes characterized by varying GT/PCL ratios appeared ivory-white
The results presented reveal that the membranes with different GT/PCL ratios can support the process of subcutaneous cartilage regeneration in an autologous swine model

Summary

Introduction

Cartilage defects in the subcutaneous environment (such as ear, nose, and trachea) due to congenital disease (microtia), cancer removal, or trauma are very common in plastic and reconstructive surgery (Wiggenhauser et al, 2017). An ideal cartilaginous substitute with a pre-designed shape and characterized by the minimum donor-site morbidity can be developed using tissue engineering technology. This can help address the problems faced when the traditional cartilage reconstructive approaches are followed (Sterodimas et al, 2009; Bichara et al, 2012). A method to achieve reliable and stable cartilage regeneration in the subcutaneous environment is yet to be developed. This is because the clinical outcomes vary from patient to patient. The fluctuations in the clinical outcomes can be potentially attributed to the inflammatory reactions triggered by the use of the engineered cartilaginous grafts for subcutaneous implantation

Methods

Results

Discussion

Conclusion