The characterization, cytotoxicity, macrophage response and tissue regeneration of decellularized cartilage in costal cartilage defects.

After harvesting multiple costal cartilages, the local defect disrupts the integrity of the chest wall and may lead to obvious thoracic complications, such as local depression and asymmetry of the bilateral thoracic height. Decellularized materials have been used for tissue reconstruction in clinical surgeries. To apply xenogenic decellularized cartilage in costal cartilage defects, porcine-derived auricular and costal cartilage was tested for characterization, cytotoxicity, macrophage response, and tissue regeneration. Most of the DNA and α-Gal were effectively removed, and the collagen was well preserved after the decellularization process. The glycosaminoglycan (GAG) content decreased significantly compared to that in untreated cartilage. The decellularized auricular cartilage had a larger pore size, more pores, and a higher degradation rate than the decellularized costal cartilage. No apparent nuclei or structural damage was observed in the extracellular matrix. The decellularized auricular cartilage had a higher cell proliferation rate and more prominent immunomodulatory effect than the other groups. Two types of decellularized cartilage, particularly decellularized auricular cartilage, promoted the tissue regeneration in the cartilage defect area, combined with noticeable cartilage morphology and increased chondrogenic gene expression. In our research, the functional components and structure of the extracellular matrix were well preserved after the decellularization process. The decellularized cartilage had better biocompatibility and suitable microenvironment for tissue regeneration in the defect area, suggesting its potential application in cartilage repair during the surgery. STATEMENT OF SIGNIFICANCE: Autologous costal cartilage has been widely used in various surgeries, while the cartilage defects after the harvesting of multiple costal cartilages may cause localized chest wall deformities. Decellularized cartilage is an ideal material that could be produced in the factory and applied in surgeries. In this study, both decellularized costal cartilage and auricular cartilage preserved original structure, functional biocompatibility, immunosuppressive effects, and promoted tissue regeneration in the cartilage defect area.

Repair of damage to the skin flap during total auricular reconstruction with tissue expansion.

INTRODUCTION: Auricular reconstruction with tissue expansion has been widely used in children with microtia. Base on the experience of using tissue expander, more patients have undergone a modified auricular reconstruction using a framework wrapped by expanded skin flap without fascial and skin graft transplantation. Skin damage is a common complication that may lead to serious outcomes, such as infection and distortion. Promptly repair is particularly important when using this modified technique. This work aims to record the site and other information on damage to the expanded skin flap, and to apply various salvage methods according to the site and stage. METHODS: From January 2017 to September 2019, 170 patients who underwent total auricular reconstruction without fascial and skin graft were followed up. All patients who had skin damage received corresponding prompt treatment. Details on the site, occurrence time, and salvage methods were noted. RESULTS: A total of 19 patients were found to have skin damage during the follow-up period. The defect size ranged from 10 mm2 to 70 mm2. Four patients had skin damage in the lower part of the skin flap combined with expander exposure. The second stage of auricular reconstruction was carried out immediately. Two patients had skin flap damage in anterior 1/3rd of the helix, seven in middle 1/3rd of the helix, four in posterior 1/3rd of the helix and two in the triangular fossa. Most of the skin damage occurred within 4-9 months after auricular reconstruction. According to the site and other factors, the expanded skin flap with the exposed cartilage was repaired using local skin flap, retroauricular skin flap, and retroauricular fascia. Patients were satisfied with the outcome of the repair. Additional skin damage and other complications were not observed after the repair operations. CONCLUSION: Skin damage is a common complication, and it should receive more attention while applying this modified auricular reconstruction using tissue expansion. The site, occurrence time, and other information provide reference to improve the reconstruction without fascial or skin graft transplantation. Salvage methods, such as retroauricular skin flap and retroauricular fascia, have been treated as highly efficient backup methods and have achieved satisfying results.

Clinical study of autologous concha cartilage transplantation to repair auricle deformities / 中华整形外科杂志

Objective@#To investigate the curative effect of auricular deformity repaired by concha cartilage.@*Methods@#From January 2017 to June 2018, 15 cases with auricular deformities were repaired using the autologous concha cartilage which combined with the retroauricular flap or retroauricular fascia with skin grafting. 9 males and 6 females, aged 10-40 with an average age of 19; 3 cases of upper 1/3 traumatic auricle defect, 2 cases of congenital Stahl's ear, 5 cases of congenital cup-shaped ear and 5 cases of congenital cryptotia.@*Results@#Total 15 patients were followed up for 12-18 months after the surgery. The area of concha cartilage resection was about 0.5 cm×1.0 cm. The shape and size of the repaired ears were similar to the healthy ear. The transplanted cartilages were not absorbed or deformed. The incision was healed well and retroauricular flap, retroauricular fascia, and skin grafting were preserved well without complications like hemorrhage, necrosis, and infection.@*Conclusions@#This method is harmless and simple, which has reliable and satisfactory effects on various auricular deformities.

The Phenolyzer Suite: Prioritizing the Candidate Genes Involved in Microtia.

OBJECTIVE: Microtia is a congenital malformation of the external ear. Great progress about the genetic of microtia has been made in recent years. This article was to prioritize the potential candidate pathogenic genes of microtia based on existing studies and reports, with the purpose of narrowing the range of following study scientifically and quickly. METHOD: A computational tool called Phenolyzer (phenotype-based gene analyzer) was used to prioritize microtia genes. Microtia, as a query term, was input in the interface of Phenolyzer. After several steps, including disease match, gene query, gene score system, seed gene growth, and gene ranking, the final results about genetic information of microtia were provided. Then we tracked details of the top 10 genes ranked by Phenolyzer on the basis of previous reports. RESULTS: We detected 10 348 genes associated with microtia or related syndromes, and 78 genes of those genes belonged to seed genes. Every gene was given a score, and the gene with higher scores was more likely influence microtia. The top 10 ranked genes included HOXA2, CHD7, CDT1, ORC1, ORC4, ORC6, CDC6, MED12, TWIST1, and GLI3. Otherwise, four gene-gene interactions were displayed. CONCLUSION: This article prioritized candidate genes of microtia for the first time. High-throughput methods provide tens of thousands of single-nucleotide variants, indels, and structural variants, and only a handful are relevant to microtia or associated syndromes. Combine the ranked potential pathogenic genes list from Phenolyzer with the results of samples provided by high-throughput methods, and more precise research directions are presented.

Bioinformatics analysis of pathogenic genes of congenital microtia / 中华整形外科杂志

Objective@#Bioinformatics methods were used to annotate the suspicious pathogenic genes of congenital microtia in detail, and construct the protein-protein interaction (PPI) networks to clarify the function and interaction of pathogenic genes, so as to predict the potential pathogenic genes.@*Methods@#The pathogenic genes of congenital microtia were searched using the mouse genome informatics (MGI). The results were summarized into the STRING database to construct PPI networks. The Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out.@*Results@#Sixty-eight congenital microtia-related pathogenic genes such as FGF8, EYA1 and HOXA2 were searched by MGI. The PPI network contained 65 nodes and 174 edges. The average node degree was 5.35. The clustering coefficient was 0.437 and the PPI enrichment P = 0. The key node proteins were screened in PPI networks. The top ten were CTNNB1, FGF8, EGFR, BCL2, PAX6, FGF3, FGF10, WNT5A, FGFR1 and MAPK1. GO analysis and KEGG pathway analysis showed: the pathogenic genes were involved in the biological process of ear morphogenesis, ear development and embryonic organ morphogenesis. They also get involved in the molecular regulation, including sequence-specific DNA binding and regulatory region DNA binding. Expression of different genes were located in nucleus and other sub-microscopic cell components. Pathogenic genes were also involved in cancer pathway, melanoma, MAPK signaling pathways, RAS signaling pathways and other signaling pathways.@*Conclusions@#By using bioinformatics tools, we constructed the PPI networks of the congenital microtia pathogenic genes, and obtained detailed GO enrichment and KEGG pathway data. The key nodes contained the confirmed pathogenic genes of congenital microtia, which preliminarily proved the feasibility of the bioinformatics method in this study. We found some nodes were closely linked with FGF and WNT, which may be potential mutant genes of congenital microtia, although further study is needed.

Identification and application of pig model with bilateral external ear defects accompanied by aural atresia / 中华整形外科杂志

Objective@#To identify a pig model with bilateral external ear defects accompanied by aural atresia and investigate its application in plastic surgery.@*Methods@#Erhualian×Shaziling F2 pig inbreeding population was introduced, and examination of external ear morphology was conducted in all individuals. Temporal computed tomography scanning and mutational detection of HOXA1 gene were conducted in one affected and one normal individuals.@*Results@#In Erhualian×Shaziling F2 pig inbreeding population, there were 57 normal and 18 affected individuals among the 75 pigs. Affected subjects presented bilateral external ear defects accompanied by aural atresia; temporal computed tomography scanning showed bilateral aural atresia and dysplasiaof middle ear; and gene detection identified homozygous mutation of HOXA1 gene.@*Conclusions@#Pig model with HOXA1 gene homozygous mutation resembles human microtia at different levels. Our findings provide the theoretical basis for its application to study further pathological mechanism for human microtia.