An analytical study of neocartilage from microtia and otoplasty surgical remnants: A possible application for BMP7 in microtia development and regeneration

Abstract

To investigate auricular reconstruction by tissue engineering means, this study compared cartilage regenerated from human chondrocytes obtained from either microtia or normal (conchal) tissues discarded from otoplasties. Isolated cells were expanded in vitro, seeded onto nanopolyglycolic acid (nanoPGA) sheets with or without addition of bone morphogenetic protein-7 (BMP7), and implanted in nude mice for 10 weeks. On specimen harvest, cartilage development was assessed by gross morphology, histology, and RT-qPCR and microarray analyses. Neocartilages from normal and microtia surgical tissues were found equivalent in their dimensions, qualitative degree of proteoglycan and elastic fiber staining, and quantitative gene expression levels of types II and III collagen, elastin, and SOX5. Microarray analysis, applied for the first time for normal and microtia neocartilage comparison, yielded no genes that were statistically significantly different in expression between these two sample groups. These results support use of microtia tissue as a cell source for normal auricular reconstruction. Comparison of normal and microtia cells, each seeded on nanoPGA and supplemented with BMP7 in a slow-release hydrogel, showed statistically significant differences in certain genes identified by microarray analysis. Such differences were also noted in several analyses comparing counterpart seeded cells without BMP7. Summary data suggest a possible application for BMP7 in microtia cartilage regeneration and encourage further studies to elucidate whether such genotypic differences translate to phenotypic characteristics of the human microtic ear. The present work advances understanding relevant to the potential clinical use of microtia surgical remnants as a suitable cell source for tissue engineering of the pinna.

Ethanol treatment of nanoPGA/PCL composite scaffolds enhances human chondrocyte development in the cellular microenvironment of tissue-engineered auricle constructs

“…Earlier investigations from this and other laboratories have established the experimental basis for such an avenue with auricular cells grown in hydrogels or on a variety of polymers designed as sheets, discs or 3D ear-shaped scaffolds [4][5][6]. The present examination follows more recent reports that human conchal and microtia chondrocytes are equivalent and may each be utilized experimentally to regenerate tissue-engineered auricular cartilage [7][8][9].…”

“…Subsequent developments in auricle reconstruction have been made through several basic science investigations, in which animal and human chondrocytes have been utilized to design engineered auricle constructs [4][5][6]. Related studies have also shown that normal (conchal) and microtia chondrocytes from otoplasty are effectively equivalent for engineered auricular cartilage regeneration [7][8][9]. Additional advances in auricle fabrication by means of preclinical studies have been reported, demonstrating satisfactory human auricle tissue-engineered grafts [10].…”

Calebin A modulates inflammatory and autophagy signals for the prevention and treatment of osteoarthritis

“…A further important balancing mechanism for cartilage tissue is the perpetuation of an intact ECM, which consists of collagen, elastins, and proteoglycans ( 39 ), and, due to its high water binding, has both a protective and nutritional function ( 40 ). As an advantage, our results pointed to CA’s support of Coll II, CSPG, and thus ECM synthesis and the expression of cartilage-specific transcription factor Sox9 ( Figure 5A ), suggesting a holistic, broad-based positive influence on PCH despite an OA-promoting environment.…”

Tissue Engineering Auricular Cartilage: A Review of Auricular Cartilage Characteristics and Current Techniques for Auricular Reconstruction

“…These co-culture systems using ADSCs or other MSCs, combined with AuCs, demonstrate advantageous paracrine signaling that may mimic the native cell-cell interactions lost through the enzymatic digestion and processing of the cells 94 . As a result, this new microenvironment is conducive to functionally stable AuCs 84,87,95,96 . Moving forward, more attention should be focused on a means to optimize this microenvironment so that a clinically relevant expansion of chondrocytes can be achieved in a consistent, predictable manner.…”