Wound-Induced Hair Follicle Neogenesis as a Promising Approach for Hair Regeneration.

The mammalian skin contains hair follicles, which are epidermal appendages that undergo periodic cycles and exhibit mini-organ features, such as discrete stem cell compartments and different cellular components. Wound-induced hair follicle neogenesis (WIHN) is the remarkable ability to regenerate hair follicles after large-scale wounding and occurs in several adult mammals. WIHN is comparable to embryonic hair follicle development in its processes. Researchers are beginning to identify the stem cells that, in response to wounding, develop into neogenic hair follicles, as well as to understand the functions of immune cells, mesenchymal cells, and several signaling pathways that are essential for this process. WIHN represents a promising therapeutic approach to the reprogramming of cellular states for promoting hair follicle regeneration and preventing scar formation. In the scope of this review, we investigate the contribution of several cell types and molecular mechanisms to WIHN.

In vitro dielectrophoresis of HEK cell migration for stimulating chronic wound epithelialization.

This article describes a dielectrophoresis (DEP)-based simulation and experimental study of human epidermal keratinocyte (HEK) cells for wounded skin cell migration toward rapid epithelialization. MyDEP is a standalone software designed specifically to study dielectric particles and cell response to an alternating current (AC) electric field. This method demonstrated that negative dielectrophoresis (NDEP ) occurs in HEK cells at a wide frequency range in highly conductive medium. The finite element method was used to characterize particle trajectory based on DEP and drag force. The performance of the system was assessed using HEK cells in a highly conductive EpiLife suspending medium. The DEP experiment was performed by applying sinusoidal wave AC potential at the peak-to-peak voltage of 10 V in a tapered aluminum microelectrode array from 100 kHz to 1 MHz. We experimentally observed the occurrence of NDEP, which attracted HEK cells toward the local electric field minima in the region of interest. The DIPP-MotionV software was used to track cell migration in the prerecorded video via an automatic marker and estimate the average speed and acceleration of the cells. The results showed that HEK cell migration was accomplished approximately at 6.43 µm/s at 100 kHz with 10 V, and FDEP caused the cells to migrate and align at the target position, which resulted in faster wound closures because of the application of an electric field frequency to HEK cells in random locations.

IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation.

BACKGROUND: Wound-induced hair follicle neogenesis (WIHN) is a phenomenon of hair neogenesis that occurs at the center of a scar when the wound area is sufficiently large. Neogenic hair follicles are separated from the pre-existing follicles at the wound edge by a hairless circular region. This WIHN study provides a unique model for developing treatments for hair loss and deciphering the mechanisms underlying organogenesis in adult mammals. METHODS: The skin of a mouse was wounded by excising a 1.5 × 1.5 cm2 square of full-thickness dorsal skin. iTRAQ technology was used to screen proteins differentially expressed between the inner and outer scar areas in a mouse model of WIHN, on post-wounding day 15, to identify the regulators of WIHN. Owing to the overexpression of interleukin-36α (IL-36α) in the de novo hair follicle growth area, the regulating effect of IL-36α overexpression in WIHN was investigated. Hair follicle stem/progenitor cells were counted by flow cytometry while the expression of hair follicle stem/progenitor cell markers (Lgr5, Lgr6, Lrig1, K15, and CD34) and that of Wnt/ß-catenin and IL-6/STAT3 pathway intermediaries was detected by qPCR and western blotting. RESULTS: We found that wounding induced IL-36α expression. Incorporation of recombinant murine IL-36α (mrIL-36α) into murine skin wounds resulted in a greater number of regenerated hair follicles (p < 0.005) and a faster healing rate. The expression of hair follicle stem/progenitor cell markers was upregulated in the mrIL-36α-injected site (p < 0.05). Additionally, mrIL-36α upregulated the IL-6/STAT3 pathway intermediaries. CONCLUSION: IL-36α is upregulated in de novo hair follicle growth areas and can promote wound epithelialization and WIHN.

Comparative evaluation of the platelet-rich fibrin bandage versus gelatin sponge-assisted palatal wound healing of free gingival graft donor site: A case series.

Periodontal plastic surgery often involves palatal donor site, thereby creating an open wound that is prone to postoperative complications such as bleeding, pain, and slow healing process. To prevent the same, platelet-rich fibrin (PRF) and gelatin sponge (GS) were utilized equally at the donor site in six patients. Patients were monitored at the 1st, 2nd, 3rd, and 4th weeks after surgery for postoperative discomfort (D), consumption of analgesics during first postoperative week, alteration of sensitivity (AS), change in feeding habits (CFH), complete wound epithelialization (CWE), and healing index (Landry et al. 1998). Two patients in the GS group showed significantly early CWE, higher healing index score, and less D, AS, and CFH postoperatively in comparison to the PRF group. It was suggested that GS can also be considered as an effective, economical, and biocompatible dressing material of choice to enhance wound healing and to minimize postoperative complications associated with the donor site.

The use of the buccal fat pad flap for oral reconstruction.

Many congenital and acquired defects occur in the maxillofacial area. The buccal fat pad flap (BFP) is a simple and reliable flap for the treatment of many of these defects because of its rich blood supply and location, which is close to the location of various intraoral defects. In this article, we have reviewed BFP and the associated anatomical background, surgical techniques, and clinical applications. The surgical procedure is simple and has shown a high success rate in various clinical applications (approximately 90%), including the closure of oroantral fistula, correction of congenital defect, treatment of jaw bone necrosis, and reconstruction of tumor defects. The control of etiologic factors, size of defect, anatomical location of defect, and general condition of patient could influence the prognosis after grafting. In conclusion, BFP is a reliable flap that can be applied to various clinical situations.

The use of the buccal fat pad flap for oral reconstruction / 대한악안면성형재건외과학회지

Many congenital and acquired defects occur in the maxillofacial area. The buccal fat pad flap (BFP) is a simple and reliable flap for the treatment of many of these defects because of its rich blood supply and location, which is close to the location of various intraoral defects. In this article, we have reviewed BFP and the associated anatomical background, surgical techniques, and clinical applications. The surgical procedure is simple and has shown a high success rate in various clinical applications (approximately 90%), including the closure of oroantral fistula, correction of congenital defect, treatment of jaw bone necrosis, and reconstruction of tumor defects. The control of etiologic factors, size of defect, anatomical location of defect, and general condition of patient could influence the prognosis after grafting. In conclusion, BFP is a reliable flap that can be applied to various clinical situations.

Comparison of Wound Healing Process between Burn and Skin Defect in a Porcine Model

PURPOSE: The purpose of this study was to develop porcine full thickness skin wound healing model of thermal burn and skin defect and to compare wound healing process between them. METHODS: Twelve thermal burns and 12 skin defect wounds were created on the back of 3 domestic pigs. A round shaped heated electric iron was contacted for 30 seconds to develop full thickness burn. Appropriate dressings were applied for 30 days after wounding. Full thickness skin biopsies were obtained for histologic analysis by a pathologist. The amount of wound discharge, the surface area of each wound, and wound culture results were compared between skin defect and burn wound. RESULTS: Of 12 burn wound sections, 7 (58%) were identified to full thickness dermal injury. Complete wound reepithelialization was seen between postburn days 21 and 28 in both wounds. The initial wound area was smaller in burn than skin defect (P<0.001, 14.4+/-0.8 cm2 vs 22.8+/-3.4 cm2). The wound area of both burn and skin defect was slightly increased for 9 days after wounding and rapidly decreased after that time. The linear advancement length of wound edge was significantly slower in burn (P=0.009, 1.06+/-0.28 vs 1.48+/-0.42 cm). The amount of wound discharge was greater in skin defect than burn (P=0.002, 35.1+/-8.3 vs 49.5+/-11.2 g). CONCLUSION: We developed a porcine model of both thermal burn and skin defect. Time for complete reepithelialization was similar but the linear advancement length of wound edge was slower in burn than skin defect wound.

Auto/paracrine nicotinergic peptides participate in cutaneous stress response to wounding.

Restoration of epidermal barrier (epithelialization), is a major component of cutaneous response to stress imposed by wounding. Learning physiologic regulation of epithelialization may lead to novel treatments of chronic wounds. The non-canonical ligands of nicotinic acetylcholine receptors SLURP (secreted mammalian Ly-6/urokinase-type plasminogen activator receptor-related proteins)-1 and -2 are produced by keratinocytes (KCs) and inflammatory cells to augment physiologic responses to non-neuronal acetylcholine, suggesting that they can affect wound epithelialization and inflammation. In this study, recombinant (r)SLURP-1 and -2 exhibited dose dependent effects on migration of cultured KCs, and monoclonal antibodies inactivating auto/paracrine SLURPs in mouse skin delayed wound epithelialization. While effects of rSLURPs on migration were opposite, with rSLURP-1 inhibiting and rSLURP-2 stimulating migration of KCs, each anti-SLURP antibody produced a negative effect on epithelialization in vivo, suggesting their more extensive than regulation of keratinocyte migration involvement in wound repair. Since inflammation plays an important role in stress response to wounding, we measured inflammation biomarkers in wounds treated with anti-SLURP antibodies. Both anti-SLURP-1 and -2 antibodies, or their mixture, caused significant elevation of wound myeloperoxidase, IL-1ß, IL-6 and TNFα. Taken together, results of this study demonstrated that SLURP-1 slows crawling locomotion of KCs, and exhibits a strong anti-inflammatory activity in wound tissue. In contrast, SLURP-2 facilitates lateral migration of KCs, but shows a lesser anti-inflammatory capacity. Thus, combined biologic activities of both SLURPs may be required for normal stress response to skin wounding, which favors clinical trial of rSLURP-1 and -2 in wounds that fail to heal.