Search Results (20)

Background/Objectives Auricular reconstruction poses significant surgical challenges in congenital and post-traumatic cases. Porous polyethylene (PPE) implants have emerged as a biocompatible alternative to the traditional autologous rib cartilage frames, offering less morbidity and a potentially stable framework. Here, we summarize the current evidence of the use of PPE auricular implants. Methods: A literature search was performed in accordance with PRISMA guidelines across several databases. Studies reporting outcomes of PPE implants in auricular reconstruction were included. Data were extracted on patient characteristics, operative details, and complication rates, along with any required interventions to address complications. Complications were classified as minor or major based on their management strategy. Results: Of 544 screened studies, 14 studies representing 1036 patients were included. PPE implant use was generally linked with favorable esthetic outcomes and high patient satisfaction (80%). Study-to-study variation in complication rates was notable, with some complication rates as high as 44% in the early 1990s. By the early 2000s, advancements in surgical methods—particularly the use of temporoparietal fascia (TPF) flaps and other flaps for optimal soft tissue coverage—had markedly reduced complication rates, with recent studies reporting rates as low as 7%. Implant exposure (6.7%) and implant fractures (ranging from 1.6% to 3.2%) were the most frequently reported problems. Conclusions: PPE auricular implants, despite decades of availability, have faced limited global adoption due to concerns over complications and longevity. Advances in surgical techniques have significantly reduced complication rates (<7%), making PPE implants a viable early intervention with favorable esthetics and negligible donor-site morbidity. Full article

Background. Removal of the rib and adjacent cartilage is a common step for exposure of the recipient chest vessels in free-flap breast reconstructions. However, this adds both short- and long-term morbidity to the procedure. We describe our experience in avoiding rib removal in microvascular breast reconstruction. Patients and Methods. We retrospectively reviewed recipient vessel preparation in free-flap breast reconstructions performed by a single surgeon (SGB). Results. A total of 556 consecutive patients, totaling 1106 flaps over 5 years, were assessed. Recipient vessels included IMA in 1068 flaps and internal mammary perforator in 38 DIEP flaps. Nine patients underwent bilateral DIEP flap breast reconstruction with a cross-chest anastomosis, where the IMA was the recipient. Also, the IMA was used in 171 patients who underwent breast reconstruction with stacked flaps. No instances of complete rib resection were reported. However, in two cases of delayed DIEP flap reconstruction without a history of radiation, resection of 20% of the rib was required for safe vessel preparation. No intraoperative complications were observed, and three flaps from different patients were lost (one PAP and two DIEPs). Conclusions. Microsurgery in free-flap breast reconstructions has greatly evolved in the past two decades. Exposure of the IMA recipient vessels typically involves the removal of a portion of the intercostal cartilage and the rib, allowing comfortable and safe management of the vasculature during dissection and anastomosis. Nonetheless, excessive removal often leads to short-term increased pain and long-term cosmetic and functional complications, such as a noticeable depression of the chest wall especially noted in thin patients with small flaps. Our approach can be safely employed to preserve the anatomy and decrease pain, allowing for outpatient performance of these procedures. Full article

Bone morphogenetic protein 6 (BMP-6) is a constituent of the TGF-β superfamily, known for its ability to stimulate bone and cartilage formation. The investigation of bmp6’s involvement in the formation of intermuscular bones in fish has garnered significant attention in recent years. The rib cage is an important skeletal structure that plays a protective function for internal organs in fish. However, there has been limited research conducted on the effects of the bmp6 gene on rib development. Silver carp is one of four major fish in China, favoured for its affordability and tender muscle. Nevertheless, the presence of numerous intermuscular bones in silver carp significantly hinders the advancement of its palatability and suitability for processing. This study showcases the effective utilisation of CRISPR/Cas9 technology for the purpose of disrupting the bmp6 gene in silver carp, leading to the creation of chimeras in the P₀ generation, marking the first instance of such an achievement. The chimeras exhibited complete viability, normal appearance, and partial intermuscular bones loss, with approximately 30% of them displaying rib bifurcation or bending. Subsequently, a transcriptome analysis on ribs of P₀ chimeras and wild-type silver carp was conducted, leading to the identification of 934 genes exhibiting differential expression, of which 483 were found to be up-regulated and 451 were found to be down-regulated. The results of the KEGG analysis revealed that the “NF-kappa B signalling pathway”, “Hippo signalling pathway”, “osteoclast differentiation”, and “haematopoietic cell lineage” exhibited enrichment and displayed a significant correlation with bone development. The up-regulated genes such as tnfα, fos, and ctgf in pathways may facilitate the proliferation and differentiation of osteoclasts, whereas the down-regulation of genes such as tgfb2 and tgfbr1 in pathways may hinder the formation and specialisation of osteoblasts, ultimately resulting in rib abnormalities. This study presents novel findings on the impact of bmp6 gene deletion on the rib development of silver carp, while simultaneously investigating the previously unexplored molecular mechanisms underlying rib defects in fish. Full article

Background: Revision rhinoplasty is a technically demanding surgical procedure that can put every surgeon in trouble. The main issue of these cases is often an altered osteocartilaginous framework following over-resection during the first intervention. Moreover, the available septal or auricular cartilage for grafting is usually not enough. This review aims to examine contemporary advances in applications of fresh frozen cartilage in rhinoplasty. Methods: A structured review of the current literature (up to December 2023) was performed on four bibliographic databases: PubMed, EMBASE, Cochrane and Medline. The search terms were combinations of “Rhinoplasty” and “Cartilage Graft”, “Allograft” or “Fresh Frozen Cartilage”. The citations of selected studies and review articles were also evaluated if present. Results: The research resulted in 152 articles, and only ten met the inclusion criteria: nine clinical articles and one in vitro study. One of the ten eligible articles was excluded. Conclusions: Fresh frozen rib cartilage proved to be a viable alternative to autologous rib grafts and irradiated homologous rib graft. Despite the higher costs, FFRG can provide a sufficient amount of tissue for grafting avoiding donor site complications and reducing the operative time and proved to have more chondrocytes and to be less prone to resorption compared to irradiated rib. Full article

Slipping rib syndrome (SRS) is a disorder that occurs when one or more of the eighth through tenth ribs become abnormally mobile. SRS is a poorly understood condition leading to a significant delay in diagnosis and therapeutic management. History and a physical exam are usually sufficient for a diagnosis of SRS. The utility of dynamic ultrasounds has also been studied as a useful diagnostic tool. Multiple surgical techniques for SRS have been described within the literature. Cartilage rib excision (CRE) has been the most common technique utilized. However, the literature has shown a high rate of recurrence and associated risks with the procedure. More recently, minimally invasive rib fixation and costal cartilage excision with vertical rib plating have been shown as successful and safe alternative techniques. This may be an effective, alternative approach to CRE in adult and pediatric populations with SRS. Full article

(1) Background: Currently, there are no pharmacological treatments that can modify the course of osteoarthritis (OA). For this reason, the present work is focused on generating knowledge for the development of new therapeutic alternatives for the treatment of OA. The objective of this work was to develop an articular hybrid implant with mesenchymal stem cells (MSCs) from sheep. The cells were differentiated into cartilage and bone using a bioabsorbable polymer with 3D printing Technology. (2) Methods: MSCs pre-differentiated to chondrocytes and osteoblasts were seeded on the 3D-printed scaffolds using polylactic acid (PLA). These were later implanted for 3 months in the thoracic ribs area and for 6 months inside the femoral head and outside of the joint capsule. After recovery, we analyzed the expressions of specific markers for bone and cartilage in the implants (3) Results: After 3 months, in lateral implants, the expression for bone markers (OPN, RUNX2) was similar to that of the control; at 6 months, we obtained a higher expression of bone markers in the implants with pre-differentiated MCS to osteoblasts outside and inside the joint. For cartilage markers, three months after the placement of the lateral implant, the expressions of Aggrecan and SOX9 COL2A1 were similar to those of the control, but the expression of COL2A1 was less; at 6 months, the three cartilage markers SOX9, Aggrecan, and COL2A1 showed significant expressions in the implant inside joint with pre-differentiated MCS to chondrocytes. (4) Conclusions: In this study, we demonstrated that the presence of pre-differentiated MSCs in the implants was a determinant factor for the expression of bone- and cartilage-specific markers at three and six months. We managed to generate a practical and easy-to-implement articular surface repair model. Full article

Cartilage grafts are well-known as being reliable in reconstructive surgery for craniofacial pathologies. The aim of this study is to describe a new technique which requires an incision smaller than 1.5 cm but is still effective for harvesting cartilage graft. Thirty-six patients who underwent costal cartilage harvesting for septorhinoplasty have been included in this study, admitted from January 2018 to December 2021. Out of 36 patients, 34 have not reported any major complications, and two cases were followed up for pneumothorax. There were no infections and no chest wall deformities. All patients reported minimal pain at the donor site. The Vancouver Scar Scale was used to evaluate the entity of the postoperative scarring phenomena. This scale total ranges from 0 (representing normal skin) to a maximum score of 13 (representing worst scar imaginable). The results were 1.53 SD ± 0.64 (on average) 1 week after the surgical procedure and 1.28 SD ± 0.45 (on average) at the 6 months follow-up. This minimally invasive method provided a valid and effective surgical technique for cartilage graft. Despite the limitations of the case series, it seems that this procedure might be comparable to other and well-established traditional procedures and could be even preferred when the minimal invasiveness is mandatory. Full article

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. Full article

Blunt high-energy chest trauma is often associated with thoracic and abdominal organ injuries. Literature for a hyperextension-distraction mechanism resulting in a costal arch fracture combined with a thoracic spine fracture is sparse. A 65-year-old male suffered a fall from a height of six meters. Initial X-ray of the chest shows left-sided high-riding diaphragm and CT scan proves anterior cartilage fracture, posterolateral serial rib fractures, traumatic intercostal pulmonary hernia, avulsion of the diaphragm, and 7th thoracic vertebral fracture. An exploratory thoracotomy was performed and the rupture of the diaphragm, creating a two-cavity injury, had been re-fixed, the pulmonary hernia was closed, and locking plate osteosyntheses of the fractured ribs including the costal arch were performed. We generally recommend surgical therapy of the thorax to restore stability in this severe injury entity. The spine was fixed dorsally using a screw-rod system. In conclusion, this thoracovertebral injury entity is associated with high overall injury severity and life-threatening thoracoabdominal injuries. Since two-cavity traumata and particularly diaphragmatic injuries are often diagnosed delayed, injuries to the costal arch can act as an indicator of severe trauma. They should be detected through clinical examination and assessment of the trauma CT in the soft tissue window. Full article

Skeletal dysplasias (SDs) are a large, heterogeneous group of mostly genetic disorders that affect the bones and cartilage, resulting in abnormal growth and development of skeletal structures. The high clinical and genetic diversity in SDs cause difficulties in prenatal diagnosis. To establish a correct prognosis and better management, it is very important to distinguish SDs with poor life-limiting prognosis or lethal SDs from other ones. Bad prognosis in foetuses is assessed on the basis of the size of the thorax, lung volumes, long bones’ length, bones’ echogenicity, bones’ angulation or presented fractures, and the concomitant presence of non-immune hydrops or visceral abnormalities. To confirm SD diagnosis and perform family genetic consultation, rapid molecular diagnostics are needed; therefore, the NGS method using a panel of genes corresponding to SD or whole-exome sequencing (WES) is commonly used. We report a case of a foetus showing long bones’ shortening and a narrow chest with short ribs, diagnosed prenatally with asphyxiating thoracic dystrophy, also known as Jeune syndrome (ATD; OMIM 208500), caused by compound heterozygous variants in the DYNC2H1 gene, identified by prenatally performed rapid-WES analysis. The missense variants in the DYNC2H1 gene were inherited from the mother (c.7289T>C; p.Ile2430Thr) and from the father (c.12716T>G; p.Leu4239Arg). The DYNC2H1 gene is one of at least 17 ATD-associated genes. This disorder belongs to the ninth group of SD, ciliopathies with major skeletal involvement. An extremely narrow, bell-shaped chest, and abnormalities of the kidneys, liver, and retinas were observed in most cases of ATD. Next to lethal and severe forms, clinically mild forms have also been reported. A diagnosis of ATD is important to establish the prognosis and management for the patient, as well as the recurrence risk for the family. Full article

To investigate the effect of the maternal gut microbiome on fetal endochondral bone formation, fetuses at embryonic day 18 were obtained from germ-free (GF) and specific-pathogen-free (SPF) pregnant mothers. Skeletal preparation of the fetuses’ whole bodies did not show significant morphological alterations; however, micro-CT analysis of the tibiae showed a lower bone volume fraction in the SPF tibia. Primary cultured chondrocytes from fetal SPF rib cages showed a lower cell proliferation and lower accumulation of the extracellular matrix. RNA-sequencing analysis showed the induction of inflammation-associated genes such as the interleukin (IL) 17 receptor, IL 6, and immune-response genes in SPF chondrocytes. These data indicate that the maternal gut microbiome in SPF mice affects fetal embryonic endochondral ossification, possibly by changing the expression of genes related to inflammation and the immune response in fetal cartilage. The gut microbiome may modify endochondral ossification in the fetal chondrocytes passing through the placenta. Full article

Osteoarthritis (OA) represents one major cause of disability worldwide still evading efficient pharmacological or cellular therapies. Severe degeneration of extracellular cartilage matrix precedes the loss of mobility and disabling pain perception in affected joints. Recent studies showed that a reduced heparan sulfate (HS) content protects cartilage from degradation in OA-animal models of joint destabilization but the underlying mechanisms remained unclear. We aimed to clarify whether low HS-content alters the mechano-response of chondrocytes and to uncover pathways relevant for HS-related chondro-protection in response to loading. Tissue-engineered cartilage with HS-deficiency was generated from rib chondrocytes of mice carrying a hypomorphic allele of Exostosin 1 (Ext1), one of the main HS-synthesizing enzymes, and wildtype (WT) littermate controls. Engineered cartilage matured for 2 weeks was exposed to cyclic unconfined compression in a bioreactor. The molecular loading response was determined by transcriptome profiling, bioinformatic data processing, and qPCR. HS-deficient chondrocytes expressed 3–6% of WT Ext1-mRNA levels. Both groups similarly raised Sox9, Col2a1 and Acan levels during maturation. However, HS-deficient chondrocytes synthesized and deposited 50% more GAG/DNA. TGFβ and FGF2-sensitivity of Ext1^gt/gt chondrocytes was similar to WT cells but their response to BMP-stimulation was enhanced. Loading induced similar activation of mechano-sensitive ERK and P38-signaling in WT and HS-reduced chondrocytes. Transcriptome analysis reflected regulation of cell migration as major load-induced biological process with similar stimulation of common (Fosl1, Itgα5, Timp1, and Ngf) as well as novel mechano-regulated genes (Inhba and Dhrs9). Remarkably, only Ext1-hypomorphic cartilage responded to loading by an expression signature of negative regulation of apoptosis with pro-apoptotic Bnip3 being selectively down-regulated. HS-deficiency enhanced BMP-sensitivity, GAG-production and fostered an anti-apoptotic expression signature after loading, all of which may protect cartilage from load-induced erosion. Full article

Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H₂O₂ caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21. Full article

Ellis-van Creveld syndrome (EVC; MIM ID #225500) is a rare congenital disease with an occurrence of 1 in 60,000. It is characterized by remarkable skeletal dysplasia, such as short limbs, ribs and polydactyly, and orofacial anomalies. With two of three patients first noted as being offspring of consanguineous marriage, this autosomal recessive disease results from mutations in one of two causative genes: EVC or EVC2/LIMBIN. The recent identification and manipulation of genetic homologs in animals has deepened our understanding beyond human case studies and provided critical insight into disease pathogenesis. This review highlights the utility of animal-based studies of EVC by summarizing: (1) molecular biology of EVC and EVC2/LIMBIN, (2) human disease signs, (3) dysplastic limb development, (4) craniofacial anomalies, (5) tooth anomalies, (6) tracheal cartilage abnormalities, and (7) EVC-like disorders in non-human species. Full article

The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1β (IL-1β) signal is an important major factor in fracture healing, whereas its relevance to retinoid receptor (an RAR inverse agonist, which promotes endochondral bone formation) remains unclear. Herein, we investigated the expressions of IL-1β and retinoic acid receptor gamma (RARγ) in a rat fracture model and the effects of IL-1β in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1β and RARγ were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1β decreases the levels of aggrecan and type II collagen but significantly increased the metalloproteinase-13 (Mmp13) mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. An RAR inverse agonist (AGN194310) inhibited IL-1β-stimulated Mmp13 and Ccn2 mRNA in a dose-dependent manner. Phosphorylated extracellular signal regulated-kinases (pERK1/2) and p-p38 mitogen-activated protein kinase (MAPK) were increased time-dependently by IL-1β treatment, and the IL-1β-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1β-stimulated expressions of Mmp13 and Ccn2 mRNA. MMP13, CCN2, and p-p38 MAPK were expressed in hypertrophic chondrocytes near the invaded vascular endothelial cells. As a whole, these results point to role of the IL-1β via p38 MAPK as important signaling in the regulation of the endochondral bone formation in fracture healing, and to the actions of RAR inverse agonists as potentially relevant modulators of this process. Full article