Immune-Inflammatory Responses of an Acellular Cartilage Matrix Biomimetic Scaffold in a Xenotransplantation Goat Model for Cartilage Tissue Engineering.

Litao Jia,Guangdong Zhou,Haiyue Jiang,Peiling Zhang,Yu Liu,Wei Zhang,Zheng Ci

doi:10.3389/fbioe.2021.667161

Abstract

The rapid development of tissue engineering and regenerative medicine has introduced a new strategy for ear reconstruction, successfully regenerating human-ear-shaped cartilage and achieving the first clinical breakthrough using a polyglycolic acid/polylactic acid (PGA/PLA) scaffold. However, its clinical repair varies greatly among individuals, and the quality of regenerated cartilage is unstable, which seriously limits further clinical application. Acellular cartilage matrix (ACM), with a cartilage-specific microenvironment, good biocompatibility, and potential to promote cell proliferation, has been used to regenerate homogeneous ear-shaped cartilage in immunocompromised nude mice. However, there is no evidence on whether ACM will regenerate homogeneous cartilage tissue in large animals or has the potential for clinical transformation. In this study, xenogeneic ACM assisted with gelatin (GT) with or without autologous chondrocytes was implanted subcutaneously into goats to establish a xenotransplantation model and compared with a PGA/PLA scaffold to evaluate the immune-inflammatory response and quality of regenerated cartilage. The results confirmed the superiority of the ACM/GT, which has the potential capacity to promote cell proliferation and cartilage formation. Although there is a slight immune-inflammatory response in large animals, it does not affect the quality of the regenerated cartilage and forms homogeneous and mature cartilage. The current study provides detailed insights into the immune-inflammatory response of the xenogeneic ACM/GT and also provides scientific evidence for future clinical application of ACM/GT in cartilage tissue engineering.

Highlights

Auricular cartilage defects, including congenital auricle malformation–microtia and acquired auricular cartilage injuries caused by various causes are very common, and the most clinical effective treatment is reconstruction using autologous costal cartilage engraving, which can cause serious complications such as surgical trauma and pneumothorax (Brent, 2002; Zhang et al, 2009; Luquetti et al, 2011, 2012; Bly et al, 2016)
The DNA content of chondrocytes on the Acellular cartilage matrix (ACM)/GT scaffold was significantly greater than on the polyglycolic acid/polylactic acid (PGA/PLA) scaffold (Figure 1G), which indicates that ACM may have the potential to promote cell proliferation
These in vitro results indicated that the ACM/GT scaffold was more favorable for cell adhesion and cell proliferation, indicating better biocompatibility of the ACM/GT scaffold when compared with PGA/PLA scaffold

Summary

Introduction

Auricular cartilage defects, including congenital auricle malformation–microtia and acquired auricular cartilage injuries caused by various causes are very common, and the most clinical effective treatment is reconstruction using autologous costal cartilage engraving, which can cause serious complications such as surgical trauma and pneumothorax (Brent, 2002; Zhang et al, 2009; Luquetti et al, 2011, 2012; Bly et al, 2016). Combined with 3D printing, cast molding, gelatin (GT) assisted crosslinking, and freeze-drying techniques, a human-ear-shaped scaffold based on ACM has been successfully prepared and used to regenerate homogeneous ear-shaped cartilage in immunocompromised nude mice (Jia et al, 2020). It is still unproven whether ACM/GT scaffolds will trigger immune-inflammatory responses like PGA/PLA scaffolds and whether ACM/GT scaffolds will regenerate homogeneous cartilage tissue in the subcutaneous environment of large animal models

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