Explore the vast range of titles available.

Objectives We conducted this study to investigate the clinical outcomes of a new self‐created technique for improving tympanoplasty. This technique, called the external auditory canal flap advancement method, aims to treat large tympanic membrane perforations, particularly those without residual edges at the anterior margin. Methods We selected 30 patients (50 ears) with large tympanic membrane perforations located in the anterior part of the tympanic membrane without residual edges. We grouped these patients based on the surgical methods used. Twenty‐six patients in the experimental group were treated with the new method of endoscopic transverse external auditory canal skin flap repair. The control group, consisting of 24 patients, received conventional endoscopic tympanoplasty. We assessed the patients for hearing, postoperative pain, and tympanic membrane healing both before and after the surgery. Results Our new method significantly improves the success rate of tympanic membrane repair and hearing levels. The healing rate of tympanic membrane repair in the experimental group was 96.15% (25/26). Patient discharge time, postoperative pain, or recovery time was not affected. Conclusions Endoscopic transverse external auditory canal flap nudge repair, as a complement to conventional otoscopic tympanoplasty, should be promoted in clinical practice. We conducted this study to investigate the clinical outcomes of a new self‐created technique for improving tympanoplasty. This technique, called the external auditory canal flap advancement method, aims to treat large tympanic membrane perforations, particularly those without residual edges at the anterior margin.

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5 + fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5 + fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid hormone-induced bone anabolism. Therefore, early perichondrial cells of the fetal cartilage are destined to become an adipogenic subset of stromal cells in postnatal diaphyseal bone marrow, supporting the theory that the adult bone marrow stromal compartments are developmentally prescribed within the two distinct cells-of-origins of the fetal bone anlage. In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. Here they show that perichondrial cells are destined to become adipocyte-biased stromal cells, indicating that marrow stromal compartments are defined by their cells of origin.

The construction and regeneration of tissue-engineered auricles are pacesetters in tissue engineering and have realized their first international clinical application. However, the unstable regeneration quality and insufficient mechanical strength have become significant obstacles impeding its clinical promotion. The perichondrium is indispensable for the nutritional and vascular supply of the underlying cartilage tissue, as well as for proper anatomical functioning and mechanical performance. This study presents a novel strategy for integrated construction of bioengineered perichondrium with bioprinted cartilage to enhance the regeneration quality and mechanical properties of tissue-engineered auricles. Simulating the anatomical structure of the native auricle designs a sandwich construction model containing bilateral perichondrium and intermediate cartilage, employing a photocrosslinkable acellular cartilage matrix and gelatin bionics matrix microenvironment, applying co-cultured auricular chondrocytes and adipose-derived stem cells creates functional cell populations, designing hatch patterns imitates microscopic arrangement structures, utilizing sacrificial materials forms interlaminar network traffic to enhance the tight connection between layers, and finally, assessing the regenerative quality of the constructs explores their feasibility and stability. The multi-level and multi-scale biomimetic construction strategy overcomes the technical limitation of the integrated construction of perichondrium-wrapped auricles and realizes biomimicry in morphology, structure, and biomechanics. Altogether, this study provides a technical reference for the hierarchical construction of complex tissues and promotes the clinical translation and application of engineered tissues or organs. [Display omitted] •Simulating auricle anatomy designs a sandwich structure with bilateral perichondrium.•Applying photocrosslinkable ACMMA and GelMA bionics matrix-specific microenvironment.•Employing co-cultured chondrocytes and ADSCs creates functional cell populations.•Designing multi-scale bioprint patterns imitates microscopic arrangement structures.•Integrated construction and regeneration of bioengineered perichondrium-wrapped auricle.

Abstract Introduction/Objective In Neurofibromatosis Type 1 (NF1), caused by mutations in the NF1 tumor-suppressor gene, children form fibrotic nonunions known as pseudarthroses following long bone fractures. Here, we integrate spatial transcriptomics of human and murine samples to investigate the pathogenesis underlying pseudoarthrosis development. Methods/Case Report We performed spatial transcriptomics on 10-day post-fracture calluses from control and periosteum-specific Nf1-deficient (Nf1Postn) mice as well as a human NF1 patient pseudarthrosis specimen. Differential gene expression and SpatialTime analyses were performed. BMP signaling was validated by immunohistochemical staining of tissues for phospho-SMAD1/5/8. Results (if a Case Study enter NA) Spatial transcriptomics detected eight cell clusters, including bone, cartilage, and muscle within mouse fracture calluses. In the control, clusters involved in fracture repair were enriched for genes associated with extracellular matrix and collagen formation (progenitor and cartilage clusters), cartilage and endochondral bone processes (ossifying perichondrium cluster), and bone remodeling (woven bone cluster). Expression of TGF-beta pathway genes was highest near the fracture plane, while BMP and Wnt pathways were activated further from the fracture. In the Nf1Postn fracture, healing was significantly delayed, lacking a robust callus and with a lower abundance of reparative skeletal cell clusters. While expression of TGF-beta pathway genes was similar to control, BMP pathway expression was minimal within the Nf1Postn fracture, which was further demonstrated by a lack of phospho-SMAD1/5/8 staining. In the human pseudarthrosis, while TGF-beta pathway genes were expressed near the fracture plane as expected, there was no enrichment of BMP pathway expression in the pseudarthrosis tissue and no significant phospho-SMAD1/5/8 staining. Conclusion Spatial transcriptomics allows for the simultaneous unbiased analysis of multiple signal transduction pathways within their native tissue environment. Our analyses 1) revealed the cellular diversity required for fracture healing, 2) demonstrated the spatially-restricted expression of key morphogenetic pathways within a fracture callus, and 3) provides in situ evidence for impaired BMP pathway activation associated with NF1 fracture pseudarthroses.

BackgroundThe aim of our study was to compare the long-term outcome after perichondrium transplantation and two-component surface replacement (SR) implants to the metacarpophalangeal (MCP) and the proximal interphalangeal (PIP) joints.MethodsWe evaluated 163 joints in 124 patients, divided into 138 SR implants in 102 patients and 25 perichondrium transplantations in 22 patients. Our primary outcome was any revision surgery of the index joint.ResultsThe median follow-up time was 6years (0-21) for the SR implants and 26years (1-37) for the perichondrium transplants. Median age at index surgery was 64years (24-82) for SR implants and 45years (18-61) for perichondium transplants. MCP joint survival was slightly better in the perichondrium group (86.7%; 95% confidence interval [CI]: 69.4-100.0) than in the SR implant group (75%; CI 53.8-96.1), but not statistically significantly so (p=0.4). PIP joint survival was also slightly better in the perichondrium group (80%; CI 55-100) than in the SR implant group (74.7%; CI 66.6-82.7), but below the threshold of statistical significance (p=0.8).ConclusionIn conclusion, resurfacing of finger joints using transplanted perichondrium is a technique worth considering since the method has low revision rates in the medium term and compares favorable to SR implants.Level of evidenceIII (Therapeutic).

The poor mechanical strength of tissue-engineered auricular cartilage which is possibly due to the lack of perichondrium limits its application in auricular reconstruction surgery. However, there is insufficient research and no reliable data to support this. This study aims to investigate the contribution of perichondrium to the mechanical strength of auricular cartilage under loading. Rabbit auricular cartilage was harvested and classified into two groups. The perichondrium was removed in Group A and was left intact in Group B. Young’s modulus, stress relaxation slope, and relaxation amout were analyzed through tensile and compressive tests using a material testing machine. Group B exhibited significantly higher Young’s modulus in both the tensile and compressive tests (p < 0.05), lower relaxation slope (p < 0.05 in tensile test, p = 0.65 in compressive test), and lower relaxation amout (p < 0.05 in tensile test, p < 0.01 in compressive test). Our results showed that the perichondrium has a definite contribution to the mechanical properties of ear cartilage. This study may provide new insights to researchers focusing on improving the mechanical strength of tissue-engineered auricular cartilage.

While prior work has established that articular cartilage arises from Prg4-expressing perichondrial cells, it is not clear how this process is specifically restricted to the perichondrium of synovial joints. We document that the transcription factor Creb5 is necessary to initiate the expression of signaling molecules that both direct the formation of synovial joints and guide perichondrial tissue to form articular cartilage instead of bone. Creb5 promotes the generation of articular chondrocytes from perichondrial precursors in part by inducing expression of signaling molecules that block a Wnt5a autoregulatory loop in the perichondrium. Postnatal deletion of Creb5 in the articular cartilage leads to loss of both flat superficial zone articular chondrocytes coupled with a loss of both Prg4 and Wif1 expression in the articular cartilage; and a non-cell autonomous up-regulation of Ctgf. Our findings indicate that Creb5 promotes joint formation and the subsequent development of articular chondrocytes by driving the expression of signaling molecules that both specify the joint interzone and simultaneously inhibit a Wnt5a positive-feedback loop in the perichondrium. Zhang et al . show that the Creb5 transcription factor regulates the formation of synovial joints, directs the genesis of articular cartilage, and regulates the shape of the ends of long bones by blocking Wnt5a expression in the perichondrium.

Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality.

Haploinsufficiency for SOX9, the master chondrogenesis transcription factor, can underlie campomelic dysplasia (CD), an autosomal dominant skeletal malformation syndrome, because heterozygous Sox9 null mice recapitulate the bent limb (campomelia) and some other phenotypes associated with CD. However, in vitro cell assays suggest haploinsufficiency may not apply for certain mutations, notably those that truncate the protein, but in these cases in vivo evidence is lacking and underlying mechanisms are unknown. Here, using conditional mouse mutants, we compared the impact of a heterozygous Sox9 null mutation (Sox9 +/−) with the Sox9 +/Y440X CD mutation that truncates the C-terminal transactivation domain but spares the DNA-binding domain. While some Sox 9+/Y440X mice survived, all Sox9 +/− mice died perinatally. However, the skeletal defects were more severe and IHH signaling in developing limb cartilage was significantly enhanced in Sox9 +/Y440X compared with Sox9 +/−. Activating Sox9 Y440X specifically in the chondrocyte–osteoblast lineage caused milder campomelia, and revealed cell- and noncell autonomous mechanisms acting on chondrocyte differentiation and osteogenesis in the perichondrium. Transcriptome analyses of developing Sox9 +/Y440X limbs revealed dysregulated expression of genes for the extracellular matrix, as well as changes consistent with aberrant WNT and HH signaling. SOX9Y440X failed to interact with β-catenin and was unable to suppress transactivation of Ihh in cell-based assays. We propose enhanced HH signaling in the adjacent perichondrium induces asymmetrically localized excessive perichondrial osteogenesis resulting in campomelia. Our study implicates combined haploinsufficiency/hypomorphic and dominant-negative actions of SOX9Y440X, cell-autonomous and noncell autonomous mechanisms, and dysregulated WNT and HH signaling, as the cause of human campomelia.

Damaged hyaline cartilage gradually decreases joint function and growing pain significantly reduces the quality of a patient’s life. The clinically approved procedure of autologous chondrocyte implantation (ACI) for treating knee cartilage lesions has several limits, including the absence of healthy articular cartilage tissues for cell isolation and difficulties related to the chondrocyte expansion in vitro. Today, various ACI modifications are being developed using autologous chondrocytes from alternative sources, such as the auricles, nose and ribs. Adult stem cells from different tissues are also of great interest due to their less traumatic material extraction and their innate abilities of active proliferation and chondrogenic differentiation. According to the different adult stem cell types and their origin, various strategies have been proposed for stem cell expansion and initiation of their chondrogenic differentiation. The current review presents the diversity in developing applied techniques based on autologous adult stem cell differentiation to hyaline cartilage tissue and targeted to articular cartilage damage therapy.