Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction.

Cellular senescence has been shown to contribute to skin ageing. However, the role of melanocytes in the process is understudied. Our data show that melanocytes are the only epidermal cell type to express the senescence marker p16INK4A during human skin ageing. Aged melanocytes also display additional markers of senescence such as reduced HMGB1 and dysfunctional telomeres, without detectable telomere shortening. Additionally, senescent melanocyte SASP induces telomere dysfunction in paracrine manner and limits proliferation of surrounding cells via activation of CXCR3-dependent mitochondrial ROS. Finally, senescent melanocytes impair basal keratinocyte proliferation and contribute to epidermal atrophy in vitro using 3D human epidermal equivalents. Crucially, clearance of senescent melanocytes using the senolytic drug ABT737 or treatment with mitochondria-targeted antioxidant MitoQ suppressed this effect. In conclusion, our study provides proof-of-concept evidence that senescent melanocytes affect keratinocyte function and act as drivers of human skin ageing.

Limited Access to Alveolar Bone Graft Surgery Following Primary Cleft Lip and Palate Repair in Indonesia: A Questionnaire-Based Qualitative Study.

INTRODUCTION: Cleft Lip and Palate is the most common craniofacial anomaly, and cleft lip and palate repair is widely performed. Alveolar cleft accompanies 75% of cleft lip cases and requires alveolar bone graft (ABG) surgery at mixed dentition age. However, studies on rates of ABG surgery are scarce. OBJECTIVE: This study aims to investigate the low popularity of ABG and orthodontic care among patients with ABG history at Cleft and Craniofacial Centre, Cipto Mangunkusumo Hospital, Jakarta. METHOD: A total of 771 patients had orofacial cleft surgeries throughout 2015 to 2021. A descriptive analysis of labioplasty, palatoplasty, and ABG surgeries was presented. Questionnaire-based qualitative analysis of ABG was obtained from the patient's guardians to evaluate the limitation and experience of conducting the surgery at our institution. RESULTS: We distributed questionnaires to 13 patients with a history of ABG. ABG accounted for only 5% of total orofacial cleft surgeries. The average age of ABG surgery and orthodontic care initiation was 11 and 11.8 years old, respectively. About 82% had access to preoperative and postoperative orthodontic care; however, only 11% received PSO before 9 years old. The satisfaction rate was 100% and 75% in ABG patients with and without orthodontic care, respectively, reporting improved feeding, speech, teeth alignment, and esthetic result. CONCLUSION: Orofacial cleft management requires a multistage, comprehensive, and multidisciplinary approach. The number of ABG surgeries is low in developing countries, attributed to unequal access to ABG and orthodontic care, suggesting that limitations of knowledge, geography, and economy play a big role in Indonesian healthcare.

Repair of Protruding Bilateral Cleft Lip and Palate With Staged Premaxilla Setback Osteotomy, Cheiloplasty, and Palatoplasty in Trisomy 17p Patient: A Review of Syndromic Clinical Characteristic.

Chromosome 17 duplication is correlated with an increased risk of developmental delay, birth defects, and intellectual disability. Here, we reported a female patient with trisomy 17 on the whole short arm with bilateral complete cleft lip and palate (BCLP). This study will review the surgical strategies to reconstruct the protruding premaxillary segment, cleft lip, and palate in trisomy 17p patient.The patient had heterozygous pathogenic duplication of chromosomal region chr17:526-18777088 on almost the entire short arm of chromosome 17. Beside the commonly found features of trisomy 17p, the patient also presented with BCLP with a prominent premaxillary portion. Premaxillary setback surgery was first performed concomitantly with cheiloplasty. The ostectomy was performed posterior to the vomero-premaxillary suture (VPS). The premaxilla was firmly adhered to the lateral segment and the viability of philtral flap was not compromised. Two-flap palatoplasty with modified intravelar veloplasty (IVV) was performed 4 months after.Successful positioning of the premaxilla segment, satisfactory lip aesthetics, and vital palatal flap was obtained from premaxillary setback, primary cheiloplasty, and subsequent palatoplasty in our trisomy 17p patient presenting with BLCP. Postoperative premaxillary stability and patency of the philtral and palatal flap were achieved. Longer follow-up is needed to evaluate the long-term effects of our surgical techniques on inhibition of midfacial growth. However, the benefits that the patient received from the surgery in improving feeding capacity and facial appearance early in life outweigh the cost of possible maxillary retrusion.

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.

Bone Growth Capacity of Human Umbilical Cord Mesenchymal Stem Cells and BMP-2 Seeded Into Hydroxyapatite/Chitosan/Gelatin Scaffold in Alveolar Cleft Defects: An Experimental Study in Goat.

OBJECTIVE: To evaluate bone regeneration in alveolar defects treated with human umbilical cord-derived mesenchymal stem cells (hUCMSCs), hydroxyapatite/chitosan/gelatin (HA/CS/Gel) scaffold, and bone morphogenic protein-2 (BMP-2) in Capra hircus models. DESIGN: Randomized posttest-only control group design. SETTING: Animal Hospital at Bogor Agricultural Institute. PARTICIPANTS: Healthy and equally treated 24 female Capra hircus/goats. INTERVENTION: Animals were randomly assigned to 3 experimental group design (iliac crest alveolar bone graft/ICABG [control], HA/Cs/Gel+BMP-2 [Novosys], and HA/Cs/Gel+BMP-2+UCMSCs). Graft materials were implanted in surgically made alveolar defects. MAIN OUTCOME MEASURES: Postoperative functional score and operating time were assessed. New bone growth, bone density, inflammatory cells recruitment, and neoangiogenesis were evaluated based on radiological and histological approach at 2 time points, week 4 and 12. Statistical analysis was done between treatment groups. RESULTS: Operating time was 34% faster and functional score 94.5% more superior in HA/Cs/Gel+BMP-2+hUCMSC group. Bone growth capacity in HA/Cs/Gel+BMP-2+UCMSCs mimicked ICABG, but ICABG showed possibility of bone loss between week 4 and 12. The HA/Cs/Gel+BMP-2+UCMSCs showed early bone repopulation and unseen inflammatory cells and angiogenesis on week 12. DISCUSSION AND CONCLUSION: The HA/Cs/Gel+BMP-2+hUCMSCs were superior in enhancing new bone growth without donor site morbidity compared to ICABG. The presence of hUCMSCs in tissue-engineered alveolar bone graft (ABG), supported with paracrine activity of the resident stem cells, initiated earlier new bone repopulation, and completed faster bone regeneration. The HA/Cs/Gel scaffold seeded with UCMSCs+BMP-2 is a safe substitute of ICABG to close alveolar bone defects suitable for patients with cleft lip, alveolus, and palate.