Large full-thickness wounded skin regeneration using 3D-printed elastic scaffold with minimal functional unit of skin

Traditional tissue engineering skin are composed of living cells and natural or synthetic scaffold. Besize the time delay and the risk of contamination involved with cell culture, the lack of autologous cell source and the persistence of allogeneic cells in heterologous grafts have limited its application. This study shows a novel tissue engineering functional skin by carrying minimal functional unit of skin (MFUS) in 3D-printed polylactide-co-caprolactone (PLCL) scaffold and collagen gel (PLCL + Col + MFUS). MFUS is full-layer micro skin harvested from rat autologous tail skin. 3D-printed PLCL elastic scaffold has the similar mechanical properties with rat skin which provides a suitable environment for MFUS growing and enhances the skin wound healing. Four large full-thickness skin defects with 30 mm diameter of each wound are created in rat dorsal skin, and treated either with tissue engineering functional skin (PLCL + Col + MFUS), or with 3D-printed PLCL scaffold and collagen gel (PLCL + Col), or with micro skin islands only (Micro skin), or without treatment (Normal healing). The wound treated with PLCL + Col + MFUS heales much faster than the other three groups as evidenced by the fibroblasts migration from fascia to the gap between the MFUS dermis layer, and functional skin with hair follicles and sebaceous gland has been regenerated. The PLCL + Col treated wound heals faster than normal healing wound, but no skin appendages formed in PLCL + Col-treated wound. The wound treated with micro skin islands heals slower than the wounds treated either with tissue engineering skin (PLCL + Col + MFUS) or with PLCL + Col gel. Our results provide a new strategy to use autologous MFUS instead “seed cells” as the bio-resource of engineering skin for large full-thickness skin wound healing.

Surgical Treatment for Recurrent Dupuytren Disease

Background: Revision procedures for recurrent Dupuytren disease (DD) can be difficult and carry a high risk of complications. Our goal was to describe surgical strategies used for cases of recurrence and report on their outcomes. Methods: We reviewed 1 surgeon’s operative cases for recurrent DD performed at 1 institution. Prior procedures included collagenase injection, percutaneous needle fasciotomy, or open surgical fasciectomy in the same digit or area of the hand. Results: From January 1981 to December 2020, 54 procedures were performed on 33 patients for recurrent DD. Most patients were men (82%), had bilateral involvement (64%) and family history (52%), and some had ectopic disease in their feet (24%). The small finger was involved in 76% of the cases, and the proximal interphalangeal (PIP) joint was involved in 83% of these digits. The procedures included 38 partial fasciectomies (72%), 12 dermofasciectomies (23%), 3 radical fasciectomies (6%), 1 of each needle fasciotomy, ray amputation, and PIP joint arthrodesis (2%). Twenty-three patients (43%) required full thickness skin grafts with an average area of 7.1 cm2 (range: 1-20 cm2). Conclusions: This study highlights the complexity of recurrent DD case management and found the treatment required for 95% of patients in this series was open partial fasciectomy with or without demofasciectomy. Full thickness skin grafting was necessary in nearly half of the cases.

Injectable Self-Healing Ceria-based Nanocomposite Hydrogel with ROS-scavenging Activity for Skin Wound Repair

Excessive reactive oxygen species (ROS) in the injured skin may impede the wound repair and skin regeneration. Herein, we develop an injectable self-healing ceria-based nanocomposite hydrogel with ROS-scavenging activity to accelerate wound healing. The nanocomposite hydrogels were successfully prepared by coating cerium oxide nanorods with polyethylenimine (PEI) and crosslinked with benzaldehyde-terminated F127 (F127-CHO) through the dynamic Schiff-base reaction (FVEC hydrogel). The results showed that the FVEC hydrogel possessed the good thermosensitivity, injectability, self-healing ability and ROS scavenging activity. The subcutaneous implantation experiments in mice confirmed that FVEC hydrogels are biocompatible and biodegradable in vivo. The full-thickness skin wound studies showed that FVEC hydrogel could significantly enhance the wound healing and epithelium regeneration with the formation of hair follicle and adipocyte tissue. This work provides a new strategy for the development of multifunctional Ce-based nanocomposite hydrogel for full-thickness skin wound healing and regeneration.

Highly Adhesive Antibacterial Bioactive Composite Hydrogels With Controllable Flexibility and Swelling as Wound Dressing for Full-Thickness Skin Healing

Polyzwitterionic hydrogels as skin wound dressings have been extensively studied owing to their superior antibacterial properties and skin adhesiveness, but their practical applications still suffer from a low adhesion strength and a high swelling ratio, which hinder the application of hydrogel for cutaneous healing. Here, we developed a novel biocompatible poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (PolySBMA) composite hydrogel with high stretchability, low swelling, strong skin adhesiveness, and antibacterial effect for enhancing wound healing. Naturally rigid polymers including quaternized chitosan methacrylate (QCSMA) and gelatin methacrylate (GelMA) are used as bioactive cross-linkers to endow PolySBMA/QCSMA/GelMA (SQG) hydrogel with a low swelling ratio and high bioactivity. The optimized hydrogel has excellent mechanical flexibility, with the ultimate tensile strength, tensile strain, modulus, and toughness of up to 344.5 kPa, 364%, 14.7 kPa, and 33.4 kJ m−3, respectively. The adhesiveness of the hydrogel to the skin tissue is as high as 38.2 kPa, which is critical for stopping the bleeding from the wound. The synergistic contributions from the PolySBMA and QCSMA endow hydrogel with good antibacterial properties against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Moreover, the natural polymer cross-linked polyzwitterionic hydrogel shows good cell activity, hemocompatibility, and histocompatibility. The in vivo full-thickness skin defect model demonstrates that the SQG hydrogel efficiently improves the granulation tissue formation and collagen deposition. In summary, such superiorly skin-adhesive antibacterial biocompatible hydrogel with controllable flexibility and swelling holds great promise as wound dressings for acute wounds.

Chitosan/alginate Hydrogel Dressing Loaded FGF/VE-cadherin: To Accelerate Full-thickness Skin Regeneration and More Normal Skin Repairs

The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40-60μm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have tremendous potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.

Autologous full-thickness skin graft as reinforcement in parastomal hernia repair: a randomised controlled trial

Background Parastomal hernia is a common complication of an enterostomy and can have a significant impact on health-related quality of life. Currently used methods of repair have high recurrence rates and considerable risk for complications. We have developed a new technique for parastomal hernia repair that uses full-thickness skin graft as reinforcement. Methods This study protocol describes a multicentre randomised controlled trial on parastomal hernia repair comparing a new full-thickness skin graft technique with conventional synthetic composite mesh as reinforcement of the abdominal wall. Patients with a symptomatic parastomal hernia will be included and followed up at 3, 12 and 36 months, with surgical complication as the primary outcome. Secondary outcomes will be recurrence rate and health-related quality of life assessed with VHPQ, EORTC C30 and CR29. Tissue biology and collagen metabolism will be investigated pre- and postoperatively using biopsies of the abdominal wall fascia and blood samples. Discussion Parastomal hernia constitutes a major clinical problem where the prospects of a good result after hernia repair are presently poor. This new method of repair with full-thickness skin grafting could be a new alternative in our surgical toolbox, but before then, it must be evaluated properly. Trial registration ClinicalTrials.gov NCT03667287. Registered on September 12, 2018

A First in Human Trial Implanting Microalgae Shows Safety of Photosynthetic Therapy for the Effective Treatment of Full Thickness Skin Wounds

Insufficient oxygen supply represents a relevant issue in several fields of human physiology and medicine. It has been suggested that the implantation of photosynthetic cells can provide oxygen to tissues in the absence of a vascular supply. This approach has been demonstrated to be successful in several in vitro and in vivo models; however, no data is available about their safety in human patients. Here, an early phase-1 clinical trial (ClinicalTrials.gov identifier: NCT03960164, https://clinicaltrials.gov/ct2/show/NCT03960164) is presented to evaluate the safety and feasibility of implanting photosynthetic scaffolds for dermal regeneration in eight patients with full-thickness skin wounds. Overall, this trial shows that the presence of the photosynthetic microalgae Chlamydomonas reinhardtii in the implanted scaffolds did not trigger any deleterious local or systemic immune responses in a 90 days follow-up, allowing full tissue regeneration in humans. The results presented here represent the first attempt to treat patients with photosynthetic cells, supporting the translation of photosynthetic therapies into clinics.Clinical Trial Registration:www.clinicaltrials.gov/ct2/show/NCT03960164, identifier: NCT03960164.

Development of an Aged Full-Thickness Skin Model Using Flexible Skin-on-a-Chip Subjected to Mechanical Stimulus Reflecting the Circadian Rhythm

The skin is subject to both intrinsic aging caused by metabolic processes in the body and extrinsic aging caused by exposure to environmental factors. Intrinsic aging is an important obstacle to in vitro experimentation as its long-term progression is difficult to replicate. Here, we accelerated aging of a full-thickness skin equivalent by applying periodic mechanical stimulation, replicating the circadian rhythm for 28 days. This aging skin model was developed by culturing a full-thickness, three-dimensional skin equivalent with human fibroblasts and keratinocytes to produce flexible skin-on-a-chip. Accelerated aging associated with periodic compressive stress was evidenced by reductions in the epidermal layer thickness, contraction rate, and secretion of Myb. Increases in β-galactosidase gene expression and secretion of reactive oxygen species and transforming growth factor-β1 were also observed. This in vitro aging skin model is expected to greatly accelerate drug development for skin diseases and cosmetics that cannot be tested on animals.

AUTOLOGOUS FULL THICKNESS SKIN GRAFT WOUND HEALING ON SPRAGUE DAWLEY RATS Reviewed From TGF-? Expression And Neutrophil Number

Introduction : Skin grafts are now one of treatment option in wound healing process that is always developing. TGF-bexpression and the number of neutrophils have an important role in healing skin graft wounds. Ozone (O3) has disinfecting properties that are effective in wound healing. Objective : Proving the effectiveness of Ozonated VCO for Full Thickness Skin Graft wound healing using parameter of TGF-b expression and neutrophil number. Method : This study is an experimental study with a post-test only design group of 40 Sprague Dawley rats performed autologous skin graft at the same time. Samples were divided randomly into 8 groups (K1 = without Ozonated VCO), (A1 = Ozonated VCO 50 mg / ml), (B1 = Ozonated VCO 100 mg / ml), (C1 = Ozonated VCO 200 mg / ml), ( K2 = without Ozonated VCO) (A2 = Ozonated VCO 50 mg / ml), (B2 = Ozonated VCO 100 mg / ml), (C2 = Ozonated VCO 200 mg / ml). Assessment of TGF-b expression and neutrophil number of tissue was performed by staining hematoxylin & eosin and immunohistochemistry on days 6 and 12 after skin graft. Results : There were significant differences (p <0.05) TGF-b expression and neutrophils number of tissue between the control group and the administration of Ozonated VCO doses of 50 mg / ml, 100 mg / ml and 200 mg / ml on days 6 and 12 post skin graft. Conclusion : The administration of Ozonated VCO effectively improve Full Thickness Skin Graft wound healing seen from macroscopic wounds, increase TGF-b expression and decrease the number of neutrophils.