Cartilage is a strong and flexible connective tissue that has many forms and functions in our body. While cartilage exhibits some forms of limited repair, for the most part, it is not particularly regenerative. Thus, in situations where patients require cartilage reconstruction, surgeons may use autografts to replace missing or damaged tissue. Cartilage tissues from different regions of the body exhibit histological differences and are in limited supply. Thus, it is important to characterize these differences to determine the most appropriate autograft source. In the case of microtia, a congenital deformity where the pinna is underdeveloped, reconstruction commonly utilizes cartilage sourced from a patient\'s own costal cartilage. This presents a potential morbidity risk. In this study, we evaluate the histological characteristics of microtia cartilage compared with normal auricular and costal cartilage obtained from human patients undergoing surgical resection. Histochemistry was used to evaluate cellularity, lipid content, and ECM content. Using a Bayesian statistical approach, we determined that while costal cartilage is the standard tissue donor, the microanatomy of microtia cartilage more closely reflects normal auricular cartilage than costal cartilage. Therefore, microtia cartilage may serve as an additional reservoir for cartilage during reconstruction.

BACKGROUND: Cartilage is an important source in supporting the structure of the nose for dorsal augmentation rhinoplasty. However, it is known that its viability is not always on the ideal level. Various wrapping materials are used to increase the strength of cartilage. Donor site morbidity, which develops following the harvesting of both cartilage and fascia as one such cover material, has attracted interest in recent years.
OBJECTIVE: In this study, we aimed to investigate the potential of dermis and tendon autografts as alternatives to fascia and cartilage.
METHODS: The sample of the study included 16 New Zealand white rabbits. The right auricular cartilage of all rabbits was amputated, and it was transformed into diced cartilage autografts. The dermis autografts from the right gluteal areas of the rabbits were deepithelialized, and lumbosacral fascia autografts were harvested from the same incision. Additionally, the Achilles tendon of each rabbit was harvested and transformed into diced tendon autografts. Four different autografts were embedded under the skin of each rabbit from 4 different pouches opened in the back of the rabbit. These autografts included diced cartilage alone (Intervention 1), fascia-wrapped cartilage (Intervention 2), dermis-wrapped cartilage (Intervention 3) and fascia-wrapped tendon (Intervention 4) autografts.
RESULTS: Intervention 1 had the most irregular appearance, the outcomes in Intervention 4 were volumetrically smaller and softer. Connective tissue formed between the diced pieces in all interventions, and it was observed that the dermis and fascia had a capsule-like appearance, and their viability was preserved. The differences between the initial and final measurements of the volumes of interventions 1, 2 and 3 were statistically significant (p < 0.05). There was no significant difference between the initial and final volumetric measurements of intervention 4 (p > 0.05). More peripheral proliferation was observed in the interventions of fascia-wrapped and dermis-wrapped diced cartilage compared to the other interventions. The intervention including fascia-wrapped diced tendon grafts had displayed more fibrosis, fragmentation and collagen fibers, while it showed a lower amount of elastic fiber. There were no significant differences among the intervention in terms of other histological parameters.
CONCLUSIONS: Tendon autografts may be a good option for dorsal augmentation rhinoplasty as they are easily harvested and have minimal donor site morbidity. Dermis autograft usage is more advantageous than fascia usage in terms of accessibility and convenience.
METHODS: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

UNASSIGNED: The restoration of auricular cartilage is a major problem of otolaryngology. The low regenerative capacity of cartilage requires alternative approaches such as cell and tissue engineering. Stem cells are one of the ways to repair auricular cartilage damages. The aim of the investigation was the regeneration of an artificial defect of the auricular cartilage of rabbits after the intravenous injection of stem cells.
UNASSIGNED: The study was carried out on rabbits. A narrow strip of auricular cartilage was surgically removed. A previously prepared suspension of homologous mesenchymal stem cells (5 million) in 0.5 ml physiological solution was injected into the vein of the opposite ear. Tissue samples from the site of the injury were collected after 1, 2, and 3 months. Histological examinations of the tissues were carried out after staining with fuchsin-eosin, azure II-eosin, and according to Weigert. In addition, the amount of interleukin-6 (IL-6) and the transforming growth factor β1 (TGF-β1) in the blood serum were determined.
UNASSIGNED: The main method of healing is the formation of a connective tissue scar. Yret, an increase of the number of fibroblasts and single islands of the newly formed auricular cartilage was found, which indicates the migration of the injected stem cells to the site of the damage and settling there. The intravenous injection of stem cells did not affect the secretion of pro-inflammatory IL-6, but significantly increased the amount of TGF-β1.
UNASSIGNED: We assume that regenerative processes were stimulated. Nevertheless, they were aimed at quickly restoring the tissue integrity through the typical stages of scar formation. The restoration of cartilage integrity requires additional regulatory factors which will determine the chondrogenic differentiation of stem cells.
UNASSIGNED: Ausies kremzliᶙ atkūrimas yra svarbi otolaringologijos problema. Kadangi kremzliᶙ regeneracijos pajėgumas yra nedidelis, būtini alternatyvūs sprendimai – pavyzdžiui, ląsteliᶙ ir audiniᶙ inžinerija. Kamieninės ląstelės yra vienas iš būdᶙ atkurti ausᶙ kremzlėms padarytą žalą. Šio tyrimo tikslas buvo dirbtinai suformuoto triušio ausies žalos defekto regeneracija po intraveninės kamieniniᶙ ląsteliᶙ injekcijos.
UNASSIGNED: Šis tyrimas atliktas su triušiais. Chirurginiu būdu buvo pašalinta siaura triušio ausies kremzliᶙ juostelė. Iš anksto buvo paruošta homologizuota mezenchiminiᶙ kamieniniᶙ ląsteliᶙ (5 milijonai) suspensija su 0,5 ml fiziologinio tirpalo. Šios suspensijos buvo įšvirkšta į kitos ausies veną. Sužeidimo vietos audiniᶙ mėginiai imti po 1, 2 ir 3 mėnesiᶙ. Surinktᶙ audiniᶙ histologinis tyrimas buvo atliktas ištepus juos su fuchsinu ir eozinu, azūro II-eozinu bei naudojant Weigerto metodiką. Be to, krau jo serume buvo nustatytas interleukino-6 (IL-6) ir transformuojančio augimo faktoriaus β1 (TGF-β1) kiekis.
UNASSIGNED: Pagrindinis gijimo metodas yra jungiamojo audinio rando susidarymas. Buvo nustatytas fibroblastᶙ skaičiaus padidėjimas. Taip pat nustatyta naujai susidariusiᶙ ausies kremzliᶙ saleliᶙ. Tai rodo, kad įšvirkštos kamieninės ląstelės migruoja į sužeidimo vietą ir ten įsikuria. Intraveninė kamieniniᶙ ląsteliᶙ injekcija nepaveikė prouždegiminio IL-6 išskyrimo, tačiau reikšmingai padidino TGF-β1 kiekį.
UNASSIGNED: Darome prielaidą, kad buvo stimuliuojami regeneraciniai procesai. Tačiau jais siekta greitai atkurti audinio integralumą įprastiniais rando susidarymo etapais. Kremzliᶙ integralumui atkurti reikia papildomᶙ reguliuojamᶙjᶙ veiksniᶙ, kurie paskatintᶙ chondrogeninę kamieniniᶙ ląsteliᶙ diferenciaciją.

Introduction: Microtia is the second most common maxillofacial birth defect worldwide. However, the involvement of long non-coding RNAs (lncRNAs) in isolated microtia is not well understood. This study aimed at identifying lncRNAs that regulate the expression of genes associated with isolated microtia. Methods: We used our microarray data to analyze the expression pattern of lncRNA in the auricular cartilage tissues from 10 patients diagnosed with isolated microtia, alongside 15 control subjects. Five lncRNAs were chosen for validation using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: We identified 4651 differentially expressed lncRNAs in the auricular cartilage from patients with isolated microtia. By Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway (GO/KEGG) analysis, we identified 27 differentially expressed genes enriched in pathways associated with microtia. In addition, we predicted 9 differentially expressed genes as potential cis-acting targets of 12 differentially expressed lncRNAs. Our findings by qRT-PCR demonstrate significantly elevated expression levels of ZFAS1 and DAB1-AS1, whereas ADIRF-AS1, HOTAIRM1, and EPB41L4A-AS1 exhibited significantly reduced expression levels in the auricular cartilage tissues of patients with isolated microtia. Conclusions: Our study sheds light on the potential involvement of lncRNAs in microtia and provides a basis for further investigation into their functional roles and underlying mechanisms.

3D bioprinting of elastic cartilage tissues that are mechanically and structurally comparable to their native counterparts, while exhibiting favorable cellular behavior, is an unmet challenge. A practical solution for this problem is the multi-material bioprinting of thermoplastic polymers and cell-laden hydrogels using multiple nozzles. However, the processing of thermoplastic polymers requires high temperatures, which can damage hydrogel-encapsulated cells. In this study, the authors developed waterborne polyurethane (WPU)-polycaprolactone (PCL) composites to allow multi-material co-printing with cell-laden gelatin methacryloyl (GelMA) hydrogels. These composites can be extruded at low temperatures (50-60 °C) and high speeds, thereby reducing heat/shear damage to the printed hydrogel-capsulated cells. Furthermore, their hydrophilic nature improved the cell behavior in vitro. More importantly, the bioprinted structures exhibited good stiffness and viscoelasticity compared to native elastic cartilage. In summary, this study demonstrated low-temperature multi-material bioprinting of WPU-PCL-based constructs with good mechanical properties, degradation time-frames, and cell viability, showcasing their potential in elastic cartilage bio-fabrication and regeneration to serve broad biomedical applications in the future.

The decellularized extracellular matrix (ECM) of cartilage is a widely used natural bioscaffold for constructing tissue-engineered cartilage due to its good biocompatibility and regeneration properties. However, current decellularization methods for accessing decellularized cartilaginous tissues require multiple steps and a relatively long duration to produce decellularized cartilage. In addition, most decellularization strategies lead to damage of the microstructure and loss of functional components of the cartilaginous matrix. In this study, a novel decellularization strategy based on a hydrostatic pressure (HP) bioreactor was introduced, which aimed to improve the efficiency of producing integral decellularized cartilage pieces by combining physical and chemical decellularization methods in a perfusing manner. Two types of cartilaginous tissues, auricular cartilage (AC) and nucleus pulposus (NP) fibrocartilage, were selected for comparison of the effects of ordinary, positive, and negative HP-based decellularization according to the cell clearance ratio, microstructural changes, ECM components, and mechanical properties. The results indicated that applying positive HP improved the efficiency of producing decellularized AC, but no significant differences in decellularization efficiency were found between the ordinary and negative HP-treated groups. However, compared with the ordinary HP treatment, the application of the positive or negative HP did not affect the efficiency of decellularized NP productions. Moreover, neither positive nor negative HP influenced the preservation of the microstructure and components of the AC matrix. However, applying negative HP disarranged the fibril distribution of the NP matrix and reduced glycosaminoglycans and collagen type II contents, two essential ECM components. In addition, the positive HP was beneficial for maintaining the mechanical properties of decellularized cartilage. The recellularization experiments also verified the good biocompatibility of the decellularized cartilage produced by the present bioreactor-based decellularization method under positive HP. Overall, applying positive HP-based decellularization resulted in a superior effect on the production of close-to-natural scaffolds for cartilage tissue engineering. Impact statement In this study, we successfully constructed a novel hydrostatic pressure (HP) bioreactor and used this equipment to produce decellularized cartilage by combining physical and chemical decellularization methods in a perfusing manner. We found that positive HP-based decellularization could improve the production efficiency of integral decellularized cartilage pieces and promote the maintenance of matrix components and mechanical properties. This new decellularization strategy exhibited a superior effect in the production of close-to-natural scaffolds and positively impacts cartilage tissue engineering.

OBJECTIVE: Analyze age-related changes in histologic features and biochemical properties of human auricular cartilage and two subsites of nasal cartilages (quadrangular cartilage and dorsal septal articulation with upper lateral cartilages).
METHODS: Prospective cross-sectional study of nasal and auricular cartilages from seventy-three (73) live donors.
METHODS: Auricular cartilage (AC), quadrangular cartilage (QC), and dorsal septal cartilage articulation (DSA) with the upper lateral cartilage (ULCs) were collected intraoperatively. Histochemical staining was used: Safranin O for glycosaminoglycans (GAGs), Verhoeff\'s for elastin, and Masson\'s trichrome for collagen. ImageJ2 software was used to calculate cell count and percent stained for each cartilage type. R studio \"ggplot\" package was used to visualize age versus cell count or percent stained.
RESULTS: Participant ages ranged from 20 to 77 years, average 46.5 years. There was a significant decline in GAGs with age for the DSA subsite, (n = 64, p < 0.001). Significant increase in collagen content with age was observed for DSA subsite (n = 66, p < 0.001) and the QC subsite (n = 64, p < 0.05). There was a statistically insignificant decline in elastin with age (n = 41, p = 0.309) for AC. Cell count declined with age at all cartilage subsites.
CONCLUSIONS: Our findings confirm that there were age-related decreases in cartilage glycosaminoglycan content, and chondrocyte cell count in both auricular and nasal cartilages. We have also confirmed that collagen content increases with age for both auricular and nasal cartilage. The histologic findings while not statistically significant in all comparisons, provides additional evidence that there is some loss of structural integrity and flexibility in nasal and auricular cartilage with aging.
METHODS: NA Laryngoscope, 134:1220-1226, 2024.

Clinically, modified autologous rib cartilage grafts and commercial implants are commonly used for intraoperative repair of auricular cartilage defects caused by injuries. However, scaffold implantation is often accompanied by various complications including absorption and collapse, resulting in undesirable clinical outcomes. Three-dimensional printed auricular cartilage scaffolds have the advantage of individual design and biofunctionality, which attracted tremendous attention in this field. In this study, to better simulate the mechanical properties of auricular cartilage, we tested PU treated by ultrasonication and high temperature for 30 min (PU-30) or 60 min (PU-60). The results indicated that the compression modulus of PU-30 was 2.21-2.48 MPa, which similar to that of natural auricular cartilage (2.22-7.23 MPa) and was chosen for subsequent experiments. And the pores of treated PU were filled with a gelatin/sodium alginate hydrogel loaded with chondrocytes. In vivo analysis using a rabbit model confirmed that implanted PU-30 scaffold filled with chondrocytes contained hydrogel successfully integrated with normal auricular cartilage, and that new cartilage was generated at the scaffold-tissue interface by histological examination. These findings illustrate that this engineered scaffold represents a potential strategy for repair of ear cartilage damage in clinical.

Background: The treatment of microtia or acquired ear deformities by surgery is a significant challenge for plastic and ENT surgeons; one of the most difficult points is constructing the scaffold for auricular reconstruction. As a type of cell with multiple differentiation potentials, stem cells play an essential role in the construction of cartilage scaffolds, and therefore have received widespread attention in ear reconstructive research. Methods: A literature search was conducted for peer-reviewed articles between 2005 and 2023 with the following keywords: stem cells; auricular cartilage; ear cartilage; conchal cartilage; auricular reconstruction, regeneration, and reparation of chondrocytes; tissue engineering in the following databases: PubMed, MEDLINE, Cochrane, and Ovid. Results: Thirty-three research articles were finally selected and their main characteristics were summarized. Adipose-derived stem cells (ADSCs), bone marrow mesenchymal stem cells (BMMSCs), perichondrial stem/progenitor cells (PPCs), and cartilage stem/progenitor cells (CSPCs) were mainly used in chondrocyte regeneration. Injecting the stem cells into the cartilage niche directly, co-culturing the stem cells with the auricular cartilage cells, and inducing the cells in the chondrogenic medium in vitro were the main methods that have been demonstrated in the studies. The chondrogenic ability of these cells was observed in vitro, and they also maintained good elasticity and morphology after implantation in vivo for a period of time. Conclusion: ADSC, BMMSC, PPC, and CSPC were the main stem cells that have been researched in craniofacial cartilage reconstruction, the regenerative cartilage performed highly similar to normal cartilage, and the test of AGA and type II collagen content also proved the cartilage property of the neo-cartilage. However, stem cell reconstruction of the auricle is still in the initial stage of animal experiments, transplantation with such scaffolds in large animals is still lacking, and there is still a long way to go.

BACKGROUND: Autologous cartilage grafts are increasingly used in the treatment of cleft lip nasal deformity, but nasal alar retraction caused by lining defects often occurs after surgery. We designed a new graft to treat unilateral cleft lip nasal deformity while avoiding nasal alar retraction.
METHODS: Nineteen patients in our hospital underwent unilateral cleft lip nasal deformity repair surgery with an auricular cartilage-skin graft. The effect of surgery was evaluated in four aspects: satisfaction with postoperative appearance, nasal aesthetic subunit indices, position of the nasal alar rim and three-dimensional spatial difference.
RESULTS: Overall satisfaction with each index was above 90%. The nasal tip angle and nasolabial angle of patients were significantly smaller after surgery than before surgery (P < 0.01). The height of the nostril on the affected side and the length of the nasal columella were greater after surgery than before surgery (P < 0.01). The spatial differences in soft tissue between the unaffected side and the affected side after surgery were significantly smaller than before surgery (P < 0.01). According to the follow-up results of 1-2 years, there were no significant retraction of the nasal alar rim (P > 0.05) and no obvious auricular deformity. All patients had a noticeable improvement in their nasal appearance.
CONCLUSIONS: The auricular cartilage-skin graft, which can not only improve the appearance of the nose but also avoid nasal alar retraction, is an ideal graft to cure unilateral cleft lip nasal deformity.
METHODS: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .