Deferiprone Stimulates Aged Dermal Fibroblasts via HIF-1α Modulation.

BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α), a transcription factor responsible for tissue homeostasis and regeneration, presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator deferiprone (DFP) at stimulating dermal fibroblasts. OBJECTIVES: The main objective of this study was to quantify the DFP concentrations capable of stimulating dermal fibroblasts in vitro and to correlate the effective DFP concentrations with the ability of DFP to penetrate the epidermis, reach the dermis, and activate HIF-1α in vivo. METHODS: We measured cell proliferation, metabolic activity, HIF-1α expression, and lactate dehydrogenase levels of both young and aged fibroblasts after a 24-hour in vitro preconditioning with DFP. In addition, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% DFP topical formulation to quantify the concentration required to reach the dermis. RESULTS: In vitro administration of iron-chelation therapy (156-312.5 µg/mL DFP ) on aged fibroblasts resulted in activation of various antiaging processes. The concentration required to reach the dermis within 24 hours was 1.5% (0.15 mg/mL), which corresponds well with the effective doses of our laboratory analyses. CONCLUSIONS: The activation of HIF-1α by DFP enhances cell metabolism, proliferation, and survival of fibroblasts while reducing lactate dehydrogenase levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, antiaging. Therefore, the antiaging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.

Lipofilling of Fingertips for Volume Defects after Fingertip Injuries.

INTRODUCTION: Regardless of the good outcomes of conservatively treated fingertip injuries, many patients complain about volume defects and hypoesthesia. Injection of autologous fat into the defect zone may resolve the volume problem and stimulate digital nerve regeneration by adipose derived stem cell transplantation. METHODS: We analyzed 5 volume defects resulting from conservatively treated fingertip injuries in 4 patients (male to female ratio, 2:2), 6 months after the injection of autologous abdominal fat into the defect zone retrospectively. The fat transplantation was performed after complete wound healing was achieved (2.5-13.5 months; mean, 6.5 months). Assessment of 2-point discrimination; finger pulp circumference; the Disability of the Arm, Shoulder, and Hand score; visual analog scale score; and a questionnaire regarding the treatment satisfaction were carried out both preoperatively and at a 6 month follow-up according to the standard of our clinic. RESULTS: In 3 patients, one session of lipofilling was sufficient to correct the contour, whereas 1 patient with 2 fingertip injuries was treated a second time. There was no significant change in finger pulp circumference, in the 2-point discrimination values and the Disability of the Arm, Shoulder, and Hand score results. There was a significant improvement in the visual analog scale scores in 4 of 5 cases, and all patients were very satisfied with the results of the procedure regarding the improvement in hand function in sports, at work and their daily routine. CONCLUSIONS: Lipofilling can be performed with little operative risks, might alleviate the patient's symptoms and reduce pain after conservative treatment of fingertip injuries.

Geographical differences in carpometacarpal joint osteoarthritis treatment of the thumb: A survey of 1138 hand surgeons from the USA and Europe.

BACKGROUND: Carpometacarpal osteoarthritis of the thumb (CMC OA) is treated with various therapeutic approaches. However, the literature remains inconclusive regarding the ideal procedure for each disease stage. In this study, we assessed the international application of surgical treatment options including CMC I implants and non-surgical treatment options for CMC OA depending on the disease stage, with a strong focus on the detection of geographical disparities. METHODS: We conducted a large international online survey with members of hand surgical societies of the International Federation of Societies for Surgery of the Hand (IFSSH). The first part of the survey asked about general therapy options of CMC OA depending on the severity of the disease, whereas the second part specifically dealt with the use of prostheses. RESULTS: We could include 10 of 56 IFSSH member societies (6807 surgeons) and received answers from 1138 members (16.7%). Significant differences were detected in an increased use of corticosteroid injections in the USA, and a growing frequency of fat injections in Europe. Regarding use and frequency of the resection arthroplasty, we found similar results in all participating countries. Prosthetic implantation showed a significant difference between the USA and Europe, with far larger numbers stated by European hand surgeons. CONCLUSION: CMC OA is treated differently in the participating countries depending on the stage of the disease. We give an insight into geographical differences in treatment paradigms, with corticosteroid injections being more prevalent in the USA, and prosthesis implantation being more frequently chosen in the selected European countries.

Polydioxanone Threads for Facial Rejuvenation: Analysis of Quality Variation in the Market.

BACKGROUND: Beside botulinum-toxin injections and hyaluronic acid fillers, thread lifts have established themselves as the third column of minimally invasive facial rejuvenation. Most commonly, barbed threads for this approach are made out of polydioxanone, a material known for decades from application in resorbable sutures. The clinical efficacy and the putative material safety of polydioxanone have fueled the popularity of thread lifts. METHODS: The present study highlights significant variation among six commercially available threads in microstructure, tensile strength, elasticity, anchoring capacity in human tissue, and biocompatibility. RESULTS: Despite their license to be marketed and sold in the European Union, some products performed significantly worse than others on material testing, and even displayed cytotoxic characteristics. CONCLUSION: The results of this study are highly relevant for clinicians and may be linked to various typical side effects of polydioxanone threads for facial rejuvenation.

Fibrin Glue Enhances Adipose-Derived Stromal Cell Cytokine Secretion and Survival Conferring Accelerated Diabetic Wound Healing.

INTRODUCTION: Although chronic wounds are a major personal and economic burden, treatment options are still limited. Among those options, adipose-derived stromal cell- (ASC-) based therapies rank as a promising approach but are restricted by the harsh wound environment. Here we use a commercially available fibrin glue to provide a deliverable niche for ASCs in chronic wounds. MATERIAL AND METHODS: To investigate the in vitro effect of fibrin glue, cultivation experiments were performed and key cytokines for regeneration were quantified. By using an established murine chronic diabetic wound-healing model, we evaluated the influence of fibrin glue spray seeding on cell survival (In Vivo Imaging System, IVIS), wound healing (wound closure kinetics), and neovascularization of healed wounds (CD31 immunohistochemistry). RESULTS: Fibrin glue seeding leads to a significantly enhanced secretion of key cytokines (SDF-1, bFGF, and MMP-2) of human ASCs in vitro. IVIS imaging showed a significantly prolonged murine ASC survival in diabetic wounds and significantly accelerated complete wound closure in the fibrin glue seeded group. CD31 immunohistochemistry revealed significantly more neovascularization in healed wounds treated with ASCs spray seeded in fibrin glue vs. ASC injected into the wound bed. CONCLUSION: Although several vehicles have shown to successfully act as cell carrier systems in preclinical trials, regulatory issues have prohibited clinical usage for chronic wounds. By demonstrating the ability of fibrin glue to act as a carrier vehicle for ASCs, while simultaneously enhancing cellular regenerative function and viability, this study is a proponent of clinical translation for ASC-based therapies.