ABSTRACT
Repair and regeneration of nasal and auricular cartilage thrust significant challenges in reconstructive surgery. The burgeoning clinical requirement is yet to endorse a satisfactory cartilage replacement matrix. In this regard, we have bioengineered cross-linked decellularized caprine conchal cartilage (DC) as biocompatible, durable, and nontoxic matrices. The DC matrices exhibited reduced DNA and sulfated glycosaminoglycan (sGAG) with a minimal effect on the collagen content. Further, histology and scanning electron micrographs revealed a significant loss of cellular bodies and the presence of a compact matrix consisting of intricate collagen fibers, when compared to unprocessed matrices. An in vitro biological assessment of the matrices exhibited an increased chondrocyte proliferation and viability with a significantly higher DNA, sGAG, and total collagen content. The matrices showed a 3-fold increase in the expression of cartilage-specific genes, namely, aggrecan, collagen II, and sox-9, and exhibited a minimal in vitro immunogenicity. Further, an in vivo assessment was performed by xenografting these caprine matrices in a rabbit model. The retrieved matrices showed a well-organized structural and cellular orientation with extracellular matrix formation after 3 months of implantation. No significant infiltration of plasma cells, macrophages, lymphocytes, and immature fibroblasts was recorded. Therefore, these affordable, resourceful, xenocompatible matrices offer a potential alternate in the repair and regeneration of nasal and auricular cartilages.
ABSTRACT
Restoration of the external ear and nose in human patients, in either congenital deformity or acquired defects, is a challenge in reconstructive surgery. Optimization of the currently available materials is necessary for rhinoplasty and microtia correction to avoid intraoperative manoeuvring and early rejection. The aim of this study was to develop cross-linked decellularized caprine conchal cartilages as biocompatible, robust, and non-toxic matrix template. The characterization of the decellularized tissue encompasses in vitro lymphoproliferation assay, cytotoxicity test, agar gel precipitation test, in vivo immunocompatibility study, histology, and determination of pro-inflammatory cytokines in animal model. Decellularized cartilage was implanted in human volunteer at R. G. Kar Medical College and Hospital, Kolkata, India, and samples were assessed histologically by retrieving those after 4 months. The processed cartilages were implanted in rhinoplasty (nine) and microtia patients (six) keeping autogenous cartilage graft as control up to 18 months after surgery. Primary outcomes were viability and safety of the material, both in animal model and human pre-application in actual site. Secondary outcomes included self-assessed clinical findings on gross examination. This study is under the ethical approval no. RKC/14 dated January 27, 2012. The in vitro cellular reactivity was less in processed cartilage protein than control. Histology of retrieved tissues in animal model and human volunteer showed no adverse reactions. Production of IL-2, IL-6, and TNF-α cytokines was lower at 4 weeks. The rhinoplasty and microtia operation in clinical patients utilizing the processed cartilage showed satisfactory recovery with improved facial look. These low cost, easily available, biocompatible, safe xenocartilage biomatrices of caprine conchal cartilage origin are very flexible in shape and size, enabling them as potential bioimplant for repair of nasal and auricular structure without any rejection or diverse biomedical applications.
