Hes1 marks peri-condensation mesenchymal cells that generate both chondrocytes and perichondrial cells in early bone development.

Bone development starts with condensations of undifferentiated mesenchymal cells that set a framework for future bones within the primordium. In the endochondral pathway, mesenchymal cells inside the condensation differentiate into chondrocytes and perichondrial cells in a SOX9-dependent mechanism. However, the identity of mesenchymal cells outside the condensation and how they participate in developing bones remain undefined. Here we show that mesenchymal cells surrounding the condensation contribute to both cartilage and perichondrium, robustly generating chondrocytes, osteoblasts, and marrow stromal cells in developing bones. Single-cell RNA-seq analysis of Prrx1-cre-marked limb bud mesenchymal cells at E11.5 reveals that Notch effector Hes1 is expressed in a mutually exclusive manner with Sox9 that is expressed in pre-cartilaginous condensations. Analysis of a Notch signaling reporter CBF1:H2B-Venus reveals that peri-condensation mesenchymal cells are active for Notch signaling. In vivo lineage-tracing analysis using Hes1-creER identifies that Hes1+ early mesenchymal cells surrounding the SOX9+ condensation at E10.5 contribute to both cartilage and perichondrium at E13.5, subsequently becoming growth plate chondrocytes, osteoblasts of trabecular and cortical bones, and marrow stromal cells in postnatal bones. In contrast, Hes1+ cells in the perichondrium at E12.5 or E14.5 do not generate chondrocytes within cartilage, contributing to osteoblasts and marrow stromal cells only through the perichondrial route. Therefore, Hes1+ peri-condensation mesenchymal cells give rise to cells of the skeletal lineage through cartilage-dependent and independent pathways, supporting the theory that early mesenchymal cells outside the condensation also play important roles in early bone development.

Comparative study of endoscopic underlay myringoplasty with or without tucking of the attached perichondrium graft when repairing large central dry perforations.

OBJECTIVE: To compare the graft success rates and hearing outcomes of underlay myringoplasty with or without perichondrium tucking of the attached perichondrium, graft perforation margins when repairing chronic large central dry perforations. STUDY DESIGN: Randomized controlled trial. MATERIAL AND METHODS: Chronic large central dry perforations were prospectively randomized to tucking perichondrium graft underlay (TPGU) and no-tucking perichondrium graft underlay (NTPG) groups. The graft outcomes and complications were compared between the two groups at 12 months postoperatively. RESULTS: In total, 61 patients with large central dry perforations were included. All patients completed 12-month follow-ups. Residual perforations occurred in 0.0 % of the TPGU group and in 12.9 % of the NTPG group (P = 0.129), and re-perforations occurred within 6 months in 0.0 % and 3.2 % of the two groups, respectively (P = 0.987). The graft success rates were 100.0 % (30/30) and 83.9 % (26/31) (P = 0.067). No significant between-group differences were observed in terms of preoperative (P = 0.547) or postoperative (P = 0.612) air bone gaps (ABGs) or mean ABG gains (P = 0.597). No graft-related complications were observed in either group during follow-up. No patients exhibited significant graft blunting or medialization; graft lateralization was noted in one patient of the NTPG group. CONCLUSIONS: Endoscopic cartilage with tucking of the attached perichondrium perforation margins during underlay myringoplasty may improve the graft success rate compared to that of the cartilage push-through technique when repairing large central dry perforations; however, the hearing improvements were comparable in the two groups.

Comparison of temporalis fascia and cartilage graft over-under myringoplasty for repairing large perforations.

OBJECTIVE: The objective of this study was to compare the operation time, graft success, audiometric outcomes and complications of over-under technique using a temporalis fascia (TMF) and cartilage grafts for the repair of large perforations. STUDY DESIGN: Randomized controlled trial. MATERIALS AND METHODS: 80 large perforations >2 quadrants of eardrum were prospectively randomized to undergo TMF over-under technique group (TFON, n = 40) or cartilage-perichondrium over-under technique group (CPON, n = 40). The graft success rate, audiometric outcomes, and complications were compared among two groups at 12 months. RESULTS: The mean operation time was 56.8 ± 4.2 (range:52-71) min in the TFON group and 37.9 ± 2.8 (range: 31-47) min in the CPON group (P < 0.001). The lost follow-up rate was 3 (7.5 %) patients in the TFON group and 2 (5.0 %) patient in the CPON group (P = 0.644). Finally, 37 patients in the TFON group and 38 patients in the CPON group were included in this study. The graft infection rate was 2 (5.4 %) patients in the TFON group and 2 (5.3 %) patient in the CPON group (P = 0.626), all the graft infection resulted in the residual perforation. The remaining residual perforation was 2 (5.4 %) patients in the TFON group and 1 (2.6 %) patient in the CPON group; the re-perforation was 3 (8.1 %) patients in the TFON group and 0 (0.0 %) patient in the CPON group. The graft success rate was 81.1 % (30/37) patients in the TFON group and 92.1 % (35/38) patient in the CPON group. The mean preoperative and 12-month postoperative ABGs were significantly different in any group (P < 0.01). However, there were no significant difference among two groups regardless of pre-or post-ABGs or ABG closure. No lateralization of the graft or blunting was noted in any group. Four (10.8 %)patients developed atelectasis and one (2.7 %) developed the EAC scarring in the TFON group. Graft cholesteatomas was found in 2 (5.4 %) patients in the TFON group and in 5 (13.2 %) patients in the CPON group (P = 0.449). Three (8.1 %) patients had temporary hypogeusia in the TFON group. CONCLUSION: Although temporalis fascia graft over-under technique obtained similar graft success rates and hearing outcomes for large chronic perforations to the cartilage-perichondrium over-under technique, temporalis fascia graft technique prolonged the operation time and increased the re-perforation and graft atelectasis. Nevertheless, the graft cholesteatomas were comparable among two techniques.

Comparison of two endoscopic perichondrium-cartilage graft underlay myringoplasty for large perforations: a randomized controlled trial.

OBJECTIVE: The objective of this study was to compare the graft outcomes and complications of two endoscopic perichondrium-cartilage graft techniques for repairing large perforations. STUDY DESIGN: Single center blinded randomized controlled trial. MATERIALS AND METHODS: 61 large perforations more than 50% of TM area were prospectively randomized to undergo the free perichondrium and free cartilage graft group (FPFC, n = 31) or perichondrium partial attachment the cartilage graft group (PPAC, n = 30). The primary outcome measures were the operation time; secondary outcome measures were the graft success rate and hearing gain at 12 months postoperatively and postoperative complications. RESULTS: All patients completed follow-up of 12 months. The mean operation time was 38.2 ± 2.3 min in the FPFC group and 37.4 ± 5.6 min in the PPAC group (P = 0.658). At postoperative 3 months, the graft success rates were 96.7% in the FPFC group and 93.3% in the PPAC group (P = 0.976). At postoperative 12 months, the graft success rates were 96.7% in the FPFC group and 83.3% in the PPAC group (P = 0.182). However, the residual and re-perforation rate with no infection was 0.0% (0/31) in the FPFC group and 16.7% (5/30) in the PPAC group (P = 0.056). No significant between-group differences were observed pre- (P = 0.842) or post- (P = 0.759) operative air bone gap (ABG) values or mean ABG gain (P = 0.886). However, granular myringitis has been noted in 6.5% in the FPFC group and in 3.3% in the PPAC group. CONCLUSIONS: This study suggested that 12-month graft success and hearing gain were comparable between the perichondrium free and partial attachment the cartilage graft techniques, nevertheless, partial attachment technique could increase residual and re-perforations.

MRI findings of growth plate fractures of the knee: are there age- and fracture-dependent differences?

OBJECTIVE: To investigate MRI findings in children with physeal fractures of the knee with respect to age, location, and articular involvement. METHODS: Children with physeal fractures who underwent knee MRI between 2008 and 2021 were included. Two radiologists retrospectively reviewed all examinations to determine articular involvement, findings of physeal instability (perichondral disruption, periosteal entrapment), and internal derangement (cruciate ligament injury, meniscal tear, chondromalacia). Independent samples t, Mann-Whitney U, Pearson's chi-square, and Fisher's exact tests were used to compare findings. RESULTS: Fifty-six patients (37 boys, 19 girls; mean age: 12.2 ± 2.5 years; 32 distal femur, 24 proximal tibial fractures) included 24(43%) intraarticular fractures. Fractures were more common in the tibia than the femur (67% versus 25%, p = 0.004) and intraarticular fractures were more common in older than younger children (13.1 ± 2.0 versus 11.5 ± 2.7 years, p = 0.01), to associate with chondromalacia (46% versus 12%, p = 0.02) and undergo surgery (33% versus 10%, p = 0.04) when compared to extraarticular fractures. Perichondral disruption (n = 44, 79%) and periosteal entrapment (n = 13, 23%) did not significantly differ based on location or articular involvement (p > 0.05). At a median follow-up of 17.5 months (interquartile range: 1.25-34), 3 patients (2 intraarticular, 1 extraarticular fractures) developed osteoarthritis, osteochondral lesion, and leg-length discrepancy from growth arrest, which required additional surgery. CONCLUSION: Intraarticular physeal fractures were more common with older children, associate with chondromalacia, and underdo surgical intervention when compared to extraarticular fractures of the knee. While MRI findings of physeal instability were common, no significant differences were found between fractures based on anatomic location or fracture pattern.

Endoscopic perichondrium-cartilage H type technique for repairing chronic kidney-shaped perforations with 3 years of follow-up.

OBJECTIVE: The objective of this study was to evaluate graft outcomes and complications of endoscopic perichondrium-cartilage H type technique for repairing chronic kidney-shaped perforation with 3 years of follow-up. MATERIAL AND METHODS: Adult patients with chronic kidney-shaped perforation underwent endoscopic perichondrium-cartilage H type technique. The graft outcomes and complications were evaluated at 36 months after surgery. RESULTS: The total of 51 ears were included in this study. The mean operation time was 31.5 ± 4.1 min. Residual perforation was seen in 2 patients, the graft success rate was 96.1 % (49/51) at postoperative 12 months. Granular myringitis was noted in 8.2 % (4/49) patients in 49 patients with graft success. The mean preoperative ABG was 23.6 ± 3.7 dB, while the mean postoperative ABG postoperatively 12 months was 12.9 ± 5.2 dB (P < 0.05), the functional success rate was 94.1 % (48/51). At postoperative 36 months, only 32 (62.7 %, 32/51) patients were followed up, while 19 (37.3 %, 19/51) patients lost followup. Of the 32 patients with followup of 36 months, the mean follow-up time was 38.2 ± 7.1 (37-46) months, re-perforation was seen in one. All 32 patients performed the postoperative CT examination at last followup, CT revealed the well pneumatization of mastoids and middle ear. CONCLUSIONS: Endoscopic cartilage-perichondrium H type technique is an alternative method for repairing chronic kidney-shaped perforations, with a highly successful, short operation time, minimally invasive procedure, and no cholesteatoma.

FGF signaling patterns cell fate at the interface between tendon and bone.

Tendon and bone are attached by a transitional connective tissue that is morphologically graded from tendinous to osseous and develops from bipotent progenitors that co-express scleraxis (Scx) and Sox9 (Scx+/Sox9+). Scx+/Sox9+ progenitors have the potential to differentiate into either tenocytes or chondrocytes, yet the developmental mechanism that spatially resolves their bipotency at the tendon-bone interface during embryogenesis remains unknown. Here, we demonstrate that development of Scx+/Sox9+ progenitors within the mammalian lower jaw requires FGF signaling. We find that loss of Fgfr2 in the mouse tendon-bone interface reduces Scx expression in Scx+/Sox9+ progenitors and induces their biased differentiation into Sox9+ chondrocytes. This expansion of Sox9+ chondrocytes, which is concomitant with decreased Notch2-Dll1 signaling, prevents formation of a mixed population of chondrocytes and tenocytes, and instead results in ectopic endochondral bone at tendon-bone attachment units. Our work shows that FGF signaling directs zonal patterning at the boundary between tendon and bone by regulating cell fate decisions through a mechanism that employs Notch signaling.

Reconstruction of the distal radioulnar joint with rib perichondrium - midterm follow-up.

BACKGROUND: Reconstruction of an osteoarthritic distal radioulnar joint (DRUJ) in patients with high physical demands and a long lifetime expectancy is challenging. A variety of methods like implant surgery and salvage procedures as partial or total ulnar head resection and the Sauve-Kapandji procedure are reasonable options in the elderly patient but not in young individuals since it often compromises manual power and stability and may cause impingement problems. Reconstruction of the DRUJ with rib perichondrium is a new treatment option with promising short-term outcome. The aim the present study was to investigate if the outcome is consistent over time. METHODS: Four female patients with a mean age of 40.5 years suffered severe unilateral osteoarthritis in the DRUJ. They underwent reconstruction of the joint with rib perichondrium transplants. Preoperatively, mean pain under manual load was 8.5 (range 7-10) and 4.2 (range 2-5) at rest, using the visual analogue scale (VAS). Range of motion (ROM) in forearm rotation was on average 118° and grip strength was 86% in comparison to the contralateral hand. The outcome was assessed at a clinical follow-up in 2016, measuring ROM, grip-strength, pain at rest and under manual load and DASH-score. Radiological examination was performed. An additional follow-up by letter was performed in 2021 using a patient-reported-outcome survey (PROS). The patients were asked to grade the ROM and grip-strength as changed or unchanged in comparison to the clinical follow-up in 2016. RESULTS: At clinical follow-up at a mean of 3.1 years (range 1-5) after surgery, pain level had decreased to VAS 1.5 (0-5) under load and all patients were pain free at rest. Forearm rotation was on average 156° (range 100-180) and grip strength was 97% of the unoperated hand. The mean DASH-score was 14.4 (0-45). An additional follow-up by letter was conducted at a mean of 7.5 years (5.5-9.5) after surgery. ROM and grip strength were reported as unchanged by all patients in relation to the previous clinical follow-up. No additional surgery or complications were reported. CONCLUSION: Reconstruction of the osteoarthritic DRU-joint with rib perichondrium transplantation can provide good clinical outcome with perseverance over time. LEVEL OF EVIDENCE: IV.

Endoscopic tympanoplasty with post-conchal perichondrium in repairing large-sized eardrum perforations.

PURPOSE: This study aimed to compare the outcomes of endoscopic tympanoplasty with post-conchal perichondrium (PCP) and microscopic tympanoplasty with temporalis fascia in repairing large-sized eardrum perforations. METHODS: We performed a retrospective chart review of 43 patients who underwent type 1 tympanoplasty for simple large-sized perforations. The patients were divided into two groups: Group I (endoscopic ear surgery with a PCP graft, 22 patients) and Group II (microscopic ear surgery with temporalis fascia, 21 patients). Graft success rate, demographic data, pre- and postoperative pure-tone average and word-recognition score, closure of the air - bone gap, and postoperative pain scale scores were compared between the two groups. RESULTS: The graft success rates in groups I and II were 86.3% and 85.7%, respectively. The mean operation time in Group I (79.8 ± 16.5 min) was significantly shorter than that in Group II (99.9 ± 26.7 min) (p = 0.006). Both groups showed significant improvements in the pure-tone average and word-recognition scores. Average closure of the air - bone gap (ABG) in groups I and II was 20.7 ± 6.9 dB and 17.6 ± 8.4 dB, respectively. The reduction in ABG in Group I had a significantly higher magnitude than in Group II at 1000 and 2000 Hz, respectively (p = 0.028 and p = 0.017). The two groups showed no significant difference in postoperative pain scores. CONCLUSION: Endoscopic tympanoplasty with PCP showed a reliable, fascia-preserved, and excellent outcome in repairing large-sized perforations.

Strategies to Convert Cells into Hyaline Cartilage: Magic Spells for Adult Stem Cells.

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.

The Effect of Perichondrium and Graft Modification on the Viability of Conchal Cartilage Graft: An Experimental Study in Rabbit.

OBJECTIVE: Cartilage grafts are widely used in reconstructing nasal deformity for structural and aesthetic purposes. Despite being immunologically privileged, cartilage grafts are susceptible to volume loss with high risk of resorption over time. Therefore, experts opt for cartilage handling modification to resolve this issue through graft dicing, wrapping, or perichondrium preservation. This study will evaluate the effect cartilage graft preparations on graft viability. DESIGN: Single-randomized post-test-only study design. SETTING: Animal Hospital at Bogor Agricultural Institute. PARTICIPANTS: Six New Zealand, male, Hycole rabbits. INTERVENTION: Conchal cartilage grafts were retrieved from 6 experimental rabbits and distributed into 3 treatment groups: diced cartilage graft (DC; control), one-sided perichondrium-attached scored cartilage (OPSC), and tube-shaped perichondrium-wrapped diced cartilage (TPDC). MAIN OUTCOME MEASURES: Macroscopic (weight and contour) and microscopic (chondroblast proliferation, graft thickness, apoptotic cells) evaluation through histological measures were recorded on week 12. Statistical analysis was done to compare between groups. RESULTS: Diced cartilage and OPSC groups showed significant weight changes on week 12 (P < .05) with OPSC presenting with the biggest difference. Diced cartilage and OPSC group showed moderate cell proliferation on week 12 while TPDC displayed most abundant apoptotic cells (5.8%; P < .05). Diced cartilage group had the highest cartilage thickness ratio (P < .05). DISCUSSION: Bare DC technique promoted graft thickness while perichondrium-attached scored cartilage showed the most abundant chondroblast proliferation and the least apoptotic cells. Perichondrium contributes to enhanced new cartilage formation. CONCLUSION: Diced cartilage graft is suitable for masking irregularity and volume augmentation, while perichondrium-attached cartilage graft is better for structural support in nasal reconstruction.

Magnetic resonance imaging of medial collateral ligament avulsion fractures of the knee in children: a potentially underestimated injury.

BACKGROUND: Literature regarding medial collateral ligament (MCL) injuries is focused on adults with superficial MCL disruptions. However, children follow different injury patterns, with avulsion fractures at ligament attachment sites occurring commonly. Such avulsions have not been characterized for pediatric MCL injuries. OBJECTIVE: To elucidate imaging findings, and review management and outcomes of pediatric MCL avulsion fractures. MATERIALS AND METHODS: We conducted a 10-year retrospective review of knee magnetic resonance (MR) imaging reports for patients younger than 16 years old diagnosed with acute MCL avulsion fracture. MR imaging was reviewed to confirm and characterize the components of the avulsion (perichondrium without or with cartilage, and/or bone) and to identify additional knee injuries. Radiographs, if available, from the time of injury were reviewed. Clinical management and patient outcomes were recorded. RESULTS: Eighteen patients (13 boys, 5 girls) incurred an acute MCL avulsion fracture. All avulsions involved the deep MCL attachment: 17 meniscofemoral and 1 meniscotibial component. Two avulsions also included the superficial MCL attachment. Nine boys had non-osseous avulsions, all radiographically occult. All girls had radiographically apparent avulsions. Three girls and three boys sustained associated knee derangements, most commonly anterior cruciate ligament (ACL) injury (n=4). All MCL avulsions were initially treated conservatively; one child required subsequent surgery for ongoing pain. CONCLUSION: Pediatric MCL avulsion fractures in this study uniformly involve the attachment of the deep MCL and can be entirely non-osseous, particularly in boys who lag in skeletal maturity, making these injuries radiographically occult. MR imaging may be required to recognize these avulsions, which can impact the duration of rest and knee bracing.

Is no de-squamatization of the TM reliable for cartilage over-underlay myringoplasty without external auditory canal packing?

OBJECTIVE: We evaluated the graft and hearing outcomes of patients with chronic perforations treated via the cartilage-perichondrium over-underlay technique without de-squamatization of the TM and external auditory canal (EAC) packing. MATERIALS AND METHODS: Thirty-nine patients with chronic perforations and residual tympanic membranes around the perforation margins were treated using the cartilage-perichondrium over-underlay technique without de-squamatization of the TM and EAC packing. Patients were followed-up for 6 months. RESULTS: For all 39 patients with unilateral perforations, the graft success rate was 100% (39/39) at 6 months after surgery. The mean air-bone gap significantly (P < 0.05) improved from 13.41 ± 8.34 dB preoperatively to 7.45 ± 3.81 dB postoperatively in patients with small and medium perforations; the mean air-bone gap significantly improved from 20.57 ± 9.41 dB preoperatively to 9.84 ± 2.41 dB postoperatively in patients with large perforations. The lateral perichondrium gradually became necrotic and crust at postoperative 2-3 months and migrated into the EAC in all patients. CONCLUSIONS: The cartilage-perichondrium over-underlay myringoplasty without de-squamatization of the TM and EAC packing is feasible, affording a high graft success rate and good hearing improvement. The lateral perichondrium may gradually become necrotic and crusted, and migrate along the EAC over time.

Reconstruction of finger joints using autologous rib perichondrium - an observational study at a single Centre with a median follow-up of 37 years.

BACKGROUND: Gratifying long-term results are difficult to achieve when reconstructing osteoarthritic finger joints. Implant surgery is the most commonly used method to restore function and dexterity. However, all types of implant have disadvantages and may be a less favorable option in some cases, especially in young patients with a long expected lifetime and high demands on manual load. Implant related complications as loosening, instability, subsidence and stiffness are the main concerns. In this context, joint reconstruction using rib perichondrium might be a reasonable alternative in selected cases. The aim of the study was to evaluate the long-term results of finger joint reconstruction using rib perichondrial transplantation. METHODS: The study group (n = 11) consisted of eight individuals reconstructed in the proximal interphalangeal (PIP) joints and three reconstructed in the metacarpophalangeal (MCP) joints during 1974-1981. All patients were evaluated at clinical visits (median: 37 years after perichondrial transplantation, range: 34-41 years) using radiographs, disability in arm-shoulder-hand (DASH) score, Visual Analog Scale (VAS), range-of-motion (ROM) and manual strength (JAMAR). RESULTS: None of the 11 patients had undergone additional surgery. All of the PIP-joints (n = 8) were almost pain-free at activity (VAS 0,6) (range 0-4), had an average range-of-motion of 41 degrees (range 5-80) and a mean DASH-score of 8,3 (range 1-51). The mean strength was 41 kg compared to 44 kg in the contralateral hand (93%). The three MCP joints were almost pain-free at activity (VAS 0,7), (range 0-1). The ROM was on average 80 degrees (range 70-90) and the mean DASH-score was 2 (range 1-3). The mean strength was 43 kg compared to 53 kg in the contralateral hand (81%). CONCLUSIONS: Perichondrium transplants restored injured PIP and MCP joints that remained essentially pain-free and mostly well-functioning without need for additional surgeries up to 41 years after the procedure. Additional studies are needed to evaluate long-term results in comparison to modern implants and to better describe the factors that determine the outcome of these procedures. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Two-component surface replacement implants compared with perichondrium transplantation for restoration of Metacarpophalangeal and proximal Interphalangeal joints: a retrospective cohort study with a mean follow-up time of 6 respectively 26 years.

BACKGROUND: The 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. METHODS: We 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. RESULTS: The median follow-up time was 6 years (0-21) for the SR implants and 26 years (1-37) for the perichondrium transplants. Median age at index surgery was 64 years (24-82) for SR implants and 45 years (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). CONCLUSION: In 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 EVIDENCE: III (Therapeutic).

It's time to recognize the perichondrium.

The perichondrium is a complex structure centered at the chondro-osseous junction of growing bones. It plays an important role in both normal skeletal development and in pathological conditions. This review illustrates the normal anatomy, function and imaging appearance of the perichondrium from fetal development to older childhood. The radiologic appearance of the perichondrium in skeletal trauma, infection and tumors in which it plays a role also are reviewed.

The Effect of Perichondrium on Biological and Biomechanical Properties of Molded Diced Cartilage Grafts.

BACKGROUND: Diced cartilage is a significant alternative approach to cartilage grafting. However, the viability and biomechanical properties of diced cartilage grafts remain to be improved, and the role of perichondrium is largely neglected. This study aimed to evaluate the histological and biomechanical effects of perichondrium on custom-shaped diced cartilage grafts constructed via a high-density porous polyethylene mold. METHODS: Seven New Zealand rabbits were used. Unilateral auricular cartilage was harvested and divided into 2 parts, with or without perichondrium, diced into 1 × 1 × 0.5 mm cubical pieces, and filled into high-density porous polyethylene molds. Three grafts with the perichondrium removed and 3 with the perichondrium preserved were implanted subcutaneously at the dorsum. The grafts underwent biomechanical and histological tests 4, 8, and 12 weeks after the implantation. RESULTS: The diced cartilage merged into integrated blocks without observable resorption in both groups at each time point. Additionally, the retention rate of weight was higher in the perichondrium-preserved group (P < 0.05). We observed regenerated cartilage that stained positively for type II collagen and glial fibrillary acidic protein (GFAP). A greater area of regenerated cartilage and higher scores of GFAP staining were observed in the perichondrium-preserved group (P < 0.05). The yield stress and modulus of elasticity were also higher in the perichondrium-preserved grafts from week 8 after implantation (P < 0.05). CONCLUSIONS: Diced cartilage grafts with a custom shape can be constructed using a high-density porous polyethylene mold. The preservation of perichondrium can improve graft viability and biomechanical properties. LEVEL OF EVIDENCE: 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 http://www.springer.com/00266.

Signaling pathways effecting crosstalk between cartilage and adjacent tissues: Seminars in cell and developmental biology: The biology and pathology of cartilage.

Endochondral ossification, the mechanism responsible for the development of the long bones, is dependent on an extremely stringent coordination between the processes of chondrocyte maturation in the growth plate, vascular expansion in the surrounding tissues, and osteoblast differentiation and osteogenesis in the perichondrium and the developing bone center. The synchronization of these processes occurring in adjacent tissues is regulated through vigorous crosstalk between chondrocytes, endothelial cells and osteoblast lineage cells. Our knowledge about the molecular constituents of these bidirectional communications is undoubtedly incomplete, but certainly some signaling pathways effective in cartilage have been recognized to play key roles in steering vascularization and osteogenesis in the perichondrial tissues. These include hypoxia-driven signaling pathways, governed by the hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF), which are absolutely essential for the survival and functioning of chondrocytes in the avascular growth plate, at least in part by regulating the oxygenation of developing cartilage through the stimulation of angiogenesis in the surrounding tissues. A second coordinating signal emanating from cartilage and regulating developmental processes in the adjacent perichondrium is Indian Hedgehog (IHH). IHH, produced by pre-hypertrophic and early hypertrophic chondrocytes in the growth plate, induces the differentiation of adjacent perichondrial progenitor cells into osteoblasts, thereby harmonizing the site and time of bone formation with the developmental progression of chondrogenesis. Both signaling pathways represent vital mediators of the tightly organized conversion of avascular cartilage into vascularized and mineralized bone during endochondral ossification.

A single-cell transcriptomic atlas of the developing chicken limb.

BACKGROUND: Through precise implementation of distinct cell type specification programs, differentially regulated in both space and time, complex patterns emerge during organogenesis. Thanks to its easy experimental accessibility, the developing chicken limb has long served as a paradigm to study vertebrate pattern formation. Through decades' worth of research, we now have a firm grasp on the molecular mechanisms driving limb formation at the tissue-level. However, to elucidate the dynamic interplay between transcriptional cell type specification programs and pattern formation at its relevant cellular scale, we lack appropriately resolved molecular data at the genome-wide level. Here, making use of droplet-based single-cell RNA-sequencing, we catalogue the developmental emergence of distinct tissue types and their transcriptome dynamics in the distal chicken limb, the so-called autopod, at cellular resolution. RESULTS: Using single-cell RNA-sequencing technology, we sequenced a total of 17,628 cells coming from three key developmental stages of chicken autopod patterning. Overall, we identified 23 cell populations with distinct transcriptional profiles. Amongst them were small, albeit essential populations like the apical ectodermal ridge, demonstrating the ability to detect even rare cell types. Moreover, we uncovered the existence of molecularly distinct sub-populations within previously defined compartments of the developing limb, some of which have important signaling functions during autopod pattern formation. Finally, we inferred gene co-expression modules that coincide with distinct tissue types across developmental time, and used them to track patterning-relevant cell populations of the forming digits. CONCLUSIONS: We provide a comprehensive functional genomics resource to study the molecular effectors of chicken limb patterning at cellular resolution. Our single-cell transcriptomic atlas captures all major cell populations of the developing autopod, and highlights the transcriptional complexity in many of its components. Finally, integrating our data-set with other single-cell transcriptomics resources will enable researchers to assess molecular similarities in orthologous cell types across the major tetrapod clades, and provide an extensive candidate gene list to functionally test cell-type-specific drivers of limb morphological diversification.

Endoscopic tympanoplasty with limited tympanomeatal flap elevation in pediatric cases: comparison of anatomic and audiological results of grafts.

OBJECTIVES: The anatomical and functional success rates of tragal cartilage perichondrium and temporal muscle fascia, in pediatric patients who underwent endoscopic type 1 tympanoplasty with limited tympanomeatal flap elevation, were compared. METHODS: In total, 35 pediatric patients (21 females, 14 males; mean age 11.0 ± 1.5 years; range 8-14 years) who underwent transcanal endoscopic type 1 tympanoplasty with limited elevation of the tympanomeatal flap were included in this study. Patients in group A received a tragal cartilage perichondrium graft and those in group B received a temporal muscle fascia graft. The groups were compared with respect to the pre- and postoperative air-bone gap (ABG) and tympanic membrane status. RESULTS: The mean preoperative and postoperative ABG were 27.0 ± 9.2 and 9.0 ± 8.5 dB in group A, and 26.8 ± 8.8 and 11.6 ± 9.2 dB in group B, respectively. The group differences in pre- and postoperative ABG values were not significant (p = 0.882 and p = 0.417, respectively). However, in both groups, the postoperative ABG was significantly lower than the preoperative ABG (both p = 0.0001). The graft retention rate was 100% in group A and 88.2% in group B; the difference was not statistically significant (p = 0.134). There was also no statistically significant difference between the pre- and postoperative bone conduction values of the patients at 0.5, 1, 2, 3 or 4 kHz (all p > 0.05). CONCLUSIONS: Our study demonstrated that in pediatric patients undergoing endoscopic tympanoplasty, both the tragal cartilage perichondrium and the temporal muscle fascia can be used successfully and safely as grafts in endoscopic type 1 tympanoplasty performed by limited tympanomeatal flap elevation.