Autologous Skin Transplantation Research Articles

Human Placenta-Derived Mesenchymal Stem Cells Combined With Artificial Dermal Scaffold Enhance Wound Healing in a Tendon-Exposed Wound of a Rabbit Model.

To overcome the difficulty of vascular regeneration in exposed tendon wounds, we combined human placenta-derived mesenchymal stem cells (hPMSCs) with an artificial dermal scaffold and assessed their role in promoting vascular regeneration and wound healing in vivo. hPMSCs were isolated from the human placenta and characterized based on their morphology, phenotypic profiles, and pluripotency. New Zealand rabbits were used to establish an exposed tendon wound model, and hPMSCs and artificial dermal scaffolds were transplanted into the wounds. The results of gross wound observations and pathological sections showed that hPMSCs combined with artificial dermal scaffold transplantation increased the vascularization area of the wound, promoted wound healing, and increased the survival rate of autologous skin transplantation. Following artificial dermal scaffold transplantation, hPMSCs accelerated the vascularization of the dermal scaffold, and the number of fibroblasts, collagen fibers, and neovascularization in the dermal scaffold after 1 week were much higher than those in the control group. Immunohistochemical staining further confirmed that the expression of the vascular endothelial cell marker, CD31, was significantly higher in the combined transplantation group than in the dermal scaffold transplantation group. Our findings demonstrated that hPMSCs seeded onto artificial dermal scaffold could facilitate vascularization of the dermal scaffold and improve tendon-exposed wound healing.

Artificial dermis combined with skin grafting for the treatment of hand skin and soft tissue defects and exposure of bone and tendon

BACKGROUND The recovery time of hand wounds is long, which can easily result in chronic and refractory wounds, making the wounds unable to be properly repaired. The treatment cycle is long, the cost is high, and it is prone to recurrence and disability. Double layer artificial dermis combined with autologous skin transplantation has been used to repair hypertrophic scars, deep burn wounds, exposed bone and tendon wounds, and post tumor wounds. AIM To investigate the therapeutic efficacy of autologous skin graft transplantation in conjunction with double-layer artificial dermis in treating finger skin wounds that are chronically refractory and soft tissue defects that expose bone and tendon METHODS Sixty-eight chronic refractory patients with finger skin and soft tissue defects accompanied by bone and tendon exposure who were admitted from July 2021 to June 2022 were included in this study. The observation group was treated with double layer artificial dermis combined with autologous skin graft transplantation (n = 49), while the control group was treated with pedicle skin flap transplantation (n = 17). The treatment status of the two groups of patients was compared, including the time between surgeries and hospital stay. The survival rate of skin grafts/flaps and postoperative wound infections were evaluated using the Vancouver Scar Scale (VSS) for scar scoring at 6 mo after surgery, as well as the sensory injury grading method and two-point resolution test to assess the recovery of skin sensation at 6 mo. The satisfaction of the two groups of patients was also compared. RESULTS Wound healing time in the observation group was significantly longer than that in the control group (P < 0.05, 27.92 ± 3.25 d vs 19.68 ± 6.91 d); there was no significant difference in the survival rate of skin grafts/flaps between the two patient groups (P > 0.05, 95.1 ± 5.0 vs 96.3 ± 5.6). The interval between two surgeries (20.0 ± 4.3 d) and hospital stay (21.0 ± 10.1 d) in the observation group were both significantly shorter than those in the control group (27.5 ± 9.3 d) and (28.4 ± 17.7 d), respectively (P < 0.05). In comparison to postoperative infection (23.5%) and subcutaneous hematoma (11.8%) in the control group, these were considerably lower at (10.2%) and (6.1%) in the observation group. When comparing the two patient groups at six months post-surgery, the excellent and good rate of sensory recovery (91.8%) was significantly higher in the observation group than in the control group (76.5%) (P < 0.05). There was also no statistically significant difference in two point resolution (P > 0.05). The VSS score in the observation group (2.91 ± 1.36) was significantly lower than that in the control group (5.96 ± 1.51), and group satisfaction was significantly higher (P < 0.05, 90.1 ± 6.3 vs 76.3 ± 5.2). CONCLUSION The combination of artificial dermis and autologous skin grafting for the treatment of hand tendon exposure wounds has a satisfactory therapeutic effect. It is a safe, effective, and easy to operate treatment method, which is worthy of clinical promotion.

Treatment of dermal ulcer with autologous fibrin glue: Two case reports of an exploratory prospective pilot study.

The healing of recurrent and refractory skin ulcers requires a long time, during which there is risk of infection, and hospital admission is occasionally required for surgical or daily conservative treatment. Therefore, the development of promising treatments that promote faster, uneventful healing is a must. Composed of cryoprecipitate and thrombin, fibrin glue has a history of surgical use for preventing bleeding and spinal fluid leakage. Moreover, in-house cryoprecipitates contain higher concentrations of coagulation factors and cytokines that may enhance wound healing than commercially available products. However, the efficacy of completely autologous fibrin glue (AFG) in tissue repair has not yet been fully demonstrated. This study aimed to evaluate the efficacy of AFG in the treatment of refractory skin ulcers in comparison with the conventional treatment. Two patients with skin ulcer on their lower extremities due to trauma or scleroderma who showed resistance to conventional treatment were included in the study. Both study participants were diagnosed with refractory skin ulcer and were ineligible for autologous skin transplantation. AFG was prepared following autologous blood donation using a Cryoseal® system. Subsequently, AFG was administered to 50% of the area of each ulcer and observed for 4 weeks in comparison with recombinant basic fibroblast growth factor with bucladesine sodium treatment that was administered to the rest of the ulcer. The skin ulcer after trauma in participant 1 showed better improvement in the AFG-treated area. Although AFG did not show superiority regarding the ulcer area of a patient with scleroderma, it guarded the continuous exudation from the edge of the swollen skin surrounding the ulcer. AFG showed effective and beneficial results for wound healing of refractory skin ulcer and prevented exudation without any severe adverse events.

Promotion of skin wound healing using hypoimmunogenic epidermal cell sheets

ObjectiveThe physiological process of wound healing is dynamic, continuous, and intricate. Nowadays, full-thickness burn wounds are treated by autologous skin transplantation. Unfortunately, when substantial burns develop, there are fewer donor sites accessible, making it difficult to satisfy the requirement for large-scale skin transplants and increasing the risk of patient mortality. This study investigated the possibility of using a newly created hypoimmunogenic epidermal cell sheet to heal skin wounds. MethodsTransfection with lentivirus was used to generate Keratinocytes (KCs) that overexpress Indoleamine 2,3-Dioxygenase (IDO). Western blotting and quantitative polymerase chain reaction were used to measure IDO levels. To evaluate the function of IDO+ keratinocytes, CCK-8 and Transwell assays were performed. In cell sheet induction media, KCs and Fibroblasts (FBs) were cultured to yield epidermal cell sheets. The full-thickness skin excisions of BALB/c mice were transplanted with epidermal cell sheets. To assess the tumorigenicity of IDO+ keratinocytes, BALB/c nude mouse xenograft models were also used. CD3 and CD31 immunofluorescence labeling of wound tissue on day 12 to identify T lymphocyte infiltration and capillary development. ELISA measurement of IL-1 and TNF-α concentrations. ResultsIDO + keratinocytes dramatically enhanced the expression levels of IDO mRNA and protein, as well as the amount of kynurenine in the conditioned media of IDO+ keratinocytes, compared to the Control and NC groups. CD8+ T cell apoptosis was considerably greater in the IDO group than in the Control and NC groups. Nevertheless, the proliferation and migratory capabilities of IDO+ keratinocytes were not substantially different from those of the Control and NC groups. In vitro cultivation of the hypoimmunogenic epidermal cell sheet was effective. In vivo transplantation experiments demonstrated that IDO+ epidermal cell sheets can effectively promote wound healing without tumorigenicity, and IDO+ epidermal cell sheets may promote wound healing by decreasing the expression levels of inflammatory factors (TNF and IL-1) in wound tissue, decreasing CD3+ T lymphocytes, and increasing infiltration and new capillaries in wound tissue. ConclusionIn this study, we successfully constructed the hypoimmunogenic epidermal cell sheet and demonstrated that the hypoimmunogenic epidermal cell sheet could accelerate wound healing.

A new way of repairing special wounds

PurposeWound repair has always been the basic method of burn surgery, but not all wounds in clinical work can regain both function and appearance. For relatively small wounds with irreversible functional damage accompanied by necrotic bone, joint and tendon exposure, and the wounds in non-functional sites with necrotic bone, tendon exposure and poor surrounding tissue conditions, the value and significance of tissue flap transplantation for wound repair are debatable. This paper discusses a new repair method as a supplementary choice for tissue flap transplantation: autologous granulation tissue and autologous thin split-thickness skin graft, which not only repairs the wound in a simple way but also avoids the cost of tissue flap transplantation. MethodsA total of 11 patients were collected from June 2019 to July 2022, with a total of 20 exposed wounds of bone, joint and tendon necrosis. During the operation, the necrotic exposed bone tissue and the completely necrotic tendon tissue were removed, and the necrotic soft tissue around the wound was completely excised until the wound appeared bleeding. We cut granulation tissue from other parts of the patient's body with a thickness of about 0.5–0.8 mm, cover the deep wound after thorough debridement with granulation tissue, and transplant autologous thin split-thickness skin to the deep wound covered with granulation tissue. The surgical area was compressed and immobilized. ResultsIn 11 patients, 20 wounds were surgically treated, and the wounds healed 15–25 days after the operation, and no bone tissue, joints, or tendons were exposed. No case underwent secondary surgery after surgery. Some wounds were treated with bedside allograft with the consent of the patient due to a small amount of residual granulation wound healing after transplantation. ConclusionUsing autologous granulation tissue and autologous thin split-thickness skin transplantation to repair some special wounds can not only repair the wounds simply and effectively but also avoid the cost of tissue flap transplantation.

Mid-Term Follow-Up Study of Children Undergoing Autologous Skin Transplantation for Burns

Deep partial and full-thickness burns require surgical treatment with autologous skin grafts after necrectomy, which is the generally accepted way to achieve permanent wound coverage. This study sought to examine the grafted and donor areas of children who underwent autologous skin transplantation, using two assessment scales to determine the severity of the scarring and the cosmetic outcome during long-term follow-up. At the Surgical Unit of the Department of Paediatrics of the University of Pécs, between 1 January 2015 and 31 December 2019, children who had been admitted consecutively and received autologous skin transplantation were analyzed. Twenty patients met the inclusion criteria in this retrospective cohort study. The authors assessed the results using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). There was a significant difference in how parents and examiners perceived the children's scars. In the evaluation of the observer scale, the most critical variables for the area of skin grafted were relief and thickness. Besides color, relief was the worst clinical characteristic on the patient scale. However, when medical professionals evaluated the donor site, significantly better results were obtained compared to the transplanted area (average observer scale score: 1.4 and 2.35, p = 0.001; VSS: 0.85 vs. 2.60, p < 0.001), yet it was similar to the graft site in the parents' opinion (Patient Scale: 2.95 and 4.45, p = 0.181).

Skin Tissue Engineering Advances in Burns: A Brief Introduction to the Past, the Present, and the Future Potential.

Burn injuries are a severe form of skin damage with a significant risk of scarring and systemic sequelae. Approximately 11 million individuals worldwide suffer burn injuries annually, with 180,000 people dying due to their injuries. Wound healing is considered the main determinant for the survival of severe burns and remains a challenge. The surgical treatment of burn wounds entails debridement of necrotic tissue, and the wound is covered with autologous skin substitutes taken from healthy donor areas. Autologous skin transplantation is still considered to be the gold standard for wound repair. However, autologous skin grafts are not always possible, especially in cases with extensive burns and limited donor sites. Allografts from human cadaver skin and xenografts from pig skin may be used in these situations to cover the wounds temporarily. Alternatively, dermal analogs are used until permanent coverage with autologous skin grafts or artificial skins can be achieved, requiring staged procedures to prolong the healing times with the associated risks of local and systemic infection. Over the last few decades, the wound healing process through tissue-engineered skin substitutes has significantly enhanced as the advances in intensive care ensuring early survival have led to the need to repair large skin defects. The focus has shifted from survival to the quality of survival, necessitating accelerated wound repair. This special volume of JBCR is dedicated to the discoveries, developments, and applications leading the reader into the past, present, and future perspectives of skin tissue engineering in burn injuries.

Reduced Elastin Fibers and Melanocyte Loss in Vitiliginous Skin Are Restored after Repigmentation by Phototherapy and/or Autologous Minigraft Transplantation

Vitiligo is a hypopigmentation disease characterized by melanocyte death in the human epidermis. However, the mechanism of vitiligo development and repigmentation is largely unknown. Dermal fiber components might play an important role in vitiligo development and repigmentation. Indeed, our preliminary study demonstrated that elastin fibers were decreased in vitiliginous skin, suggesting that the elastin fiber is one of the factors involved in vitiligo development and repigmentation. To confirm our hypothesis, we investigated whether elastin fibers can be restored after treatment using phototherapy and/or autologous skin transplantation. Punch biopsies from 14 patients of stable nonsegmental vitiligo vulgaris were collected from nonlesional, lesional, and repigmented skin, and processed to dopa and combined dopa-premelanin reactions. Melanocytes positive to the dopa reaction and melanoblasts/melanocytes positive to the combined dopa-premelanin reaction were surveyed. Moreover, elastin fibers were detected by Victoria blue staining. Numerous melanocytes and melanoblasts were observed in the epidermis of repigmented skin after the treatment. Moreover, in the dermis of repigmented skin, elastin fibers were completely recovered or even upregulated. These results suggest that melanocyte loss in the vitiliginous skin, as well as melanocyte differentiation in repigmented skin, may be at least in part regulated by elastin fibers in the dermis.

Bioprinted Gelatin-Recombinant Type III Collagen Hydrogel Promotes Wound Healing.

Artificial skins are biomaterials that can replace the lost skin or promote the regeneration of damaged skin. Skin regenerative biomaterials are highly applauded because they can exempt patients with severe burns from the painful procedure of autologous skin transplantation. Notwithstanding decades of research, biocompatible, degradable, and printable biomaterials that can effectively promote skin regeneration as a transplantation replacement in clinical use are still scarce. Here, we report one type of all-protein hydrogel material as the product of the enzymatic crosslinking reaction of gelatin and a recombinant type III collagen (rColIII) protein. Doping the rColIII protein in gelatin reduces the inflammatory response as an implant underneath the skin. The all-protein hydrogel can be bioprinted as scaffolds to support the growth and proliferation of 3T3 fibroblast cells. The hydrogel used as a wound dressing promotes wound healing in a rat model of skin damage, showing a faster and healthier recovery than the controls. The rColIII protein in the hydrogel has been shown to play a critical role in skin regeneration. Altogether, this work manifests the development of all-protein gelatin-rColIII hydrogel and demonstrates its use in wound healing. The gelatin-collagen hydrogel wound dressing thereby may become a promising treatment of severe wounds in the future.

The surgical approach to Pyoderma gangrenosum: A retrospective monocenter study.

Pyoderma gangrenosum is a diagnosis of exclusion. It occurs rarely and is frequently misdiagnosed. It can result in severe tissue loss, particularly in surgical units with little experience. Nevertheless, surgical treatment might be necessary for reconstruction, once the progression of these wounds is controlled. We aimed to characterize medical findings in Pyoderma patients with extensive defects to assess the surgical procedures and their outcome. A retrospective study was conducted at our centre over an 18-year period. Inclusion criteria were the diagnosis of Pyoderma gangrenosum and at least one surgical intervention. Descriptive statistics were used to analyse the data. Sixteen patients were included. The mean size of the lesions was noted with 12 × 8 cm. Surgical procedures comprised debridements/necrectomies, allograft conditioning, negative pressure wound therapy, skin grafts, and microvascular free flaps. Seven patients were discharged with healed wounds, six with minor wound healing disturbances. Three patients succumbed to their underlying diseases. Drug-based therapy can stop the progress of Pyoderma, but severe tissue loss can be a persistent problem. According to our data, reconstructive-surgical treatments (debridement, autologous and allogenous skin transplantation and microvascular free flaps) act as an integral component of the therapy and can be safe options for selected patients. Furthermore, we provide an algorithm that we follow at our department in severe cases.

Evaluation of a cross-linked versus non-cross-linked collagen matrix in full-thickness skin defects

Autologous skin transplantation is the gold standard for treatment of full-thickness skin defects such as deep burn injuries, but has the disadvantages of limited donor sites and donor site morbidities. Alternative skin replacement products, such as xenografts and allografts, are not a permanent solution. Numerous manufactured skin substitutes already show promising approaches, but have limited efficacy. Therefore, wound dressings adaptable to the physiology of wound healing are still needed.In a randomized controlled in vivo study, a newly designed biocompatible collagen nonwoven matrix was compared to the Integra® bilayer dermal substitute and untreated controls in 48 full-thickness skin defects in a swine model.The take of all templates was complete, and all the tissue-engineered products accelerated dermal wound healing compared to the untreated controls, as identified by planimetric measurements. The higher collagen dose treatments and Integra®-covered wounds developed the thickest, cell-rich neoepidermal tissue in histological examination.The innovative biocompatible collagen matrix is flexibly applicable and modifiable, and offers potential as a carrier membrane for therapeutic supplemental products such as growth factors to further develop effective wound dressings.

An Open-Label Study of Low-Level Laser Therapy Followed by Autologous Fibroblast Transplantation for Healing Grade 3 Burn Wounds in Diabetic Patients.

Introduction: Low-level laser therapy (LLLT) has been used as an effective therapeutic modality since the mid-1960s. Although there have been several clinical studies using LLLT in wound healing, especially diabetic, pressure and venous ulcers, there are few reports of using this technique in burn ulcers. Autologous fibroblast transplantation is a novel treatment for patients with burns or venous ulcers. In this study for the first time, we used LLLT along with autologous fibroblast skin transplantation to treat grade 3 burn ulcers in diabetic patients. This case series describes the successful management of grade 3 burn ulcers in 10 diabetic patients using autologous fibroblast transplantation along with LLLT. Methods: After the approval of the Tehran University Ethics Committee (IR.TUMS.REC.1394.1683) and the Iran Registry of Clinical Trials (IRCT2016050226069N3), 10 diabetic patients with 10 grade 3 burn ulcers, who were a candidate for skin graft surgery, entered the study. Donor skin was biopsied using a 3 mm punch. Fibroblasts were extracted and cultured in vitro in the GMP Technique laboratory. The patients were treated using LLLT in 3-4 weeks during the time that fibroblast cultures became ready to use. Laser irradiation was done using red light, 650 nm, 150 mW, 1 J/cm2 for the bed of the ulcer and infra-red light 808 nm, 200 mW, 6 J/cm2 for the margins every other day for 10 sessions. Results: The mean wound size before treatment was 16.28 cm2 . All patients' burn wounds healed completely after 10-12 weeks. Conclusion: We conclude that this method can be used as an effective method for treating large wounds, especially in complicated patients including the diabetics.

Analysis of clinical effects of artificial dermis in functional reconstruction in the late stage of extremely severe burn

Objective: To explore the clinical effects of artificial dermis combined with autologous split-thickness skin transplantation in the treatment of functional reconstruction in the late stage of extremely severe burn. Methods: From May 2015 to May 2017, medical records of 40 patients with limited activity after scar hyperplasia and conforming to the study criteria, injured in August 2nd Kunshan factory aluminum dust explosion accident in 2014, and had surgeries in our hospital and rehabilitation treatment in our hospital's alliance rehabilitation hospital, Rehabilitation Hospital of Kunshan Zhou City, were retrospectively analyzed. According to the treatment methods, 20 patients (12 males and 8 females, aged 20 to 45 years) were enrolled in artificial dermis group. They were conducted with stage Ⅰ functional site scar loosening and artificial dermis (PELNAC) implanting+ stage Ⅱ transplantation of autologous split-thickness skin. Another 20 patients (14 males and 6 females, aged 20 to 45 years) were enrolled in conventional skin grafting group. They were conducted with stage Ⅰ functional site scar loosening and transplantation of autologous thin medium-thickness skin. After 5 days of autologous skin transplantation, the survival rates of autologous skin in patients of 2 groups were calculated. The autologous skin infection and complete healing time of skin grafting area in patients of 2 groups were recorded. In 3, 6, and 10 months after autologous skin transplantation, the Vancouver Scar Scale (VSS) was used to assess the scar condition of recipient site in patients of 2 groups. The complete healing time of donor site in patients of 2 groups was recorded. In 10 months after autologous skin transplantation, VSS was used to assess the scar condition of donor site in patients of 2 groups. In 12 months after autologous skin transplantation, the functional recovery of surgical function reconstruction site in patients of 2 groups was evaluated and rated. Data were processed with t test, analysis of variance for repeated measurement, Wilcoxon rank-sum test, chi-square test, Fisher's exact probability test, and Bonferroni correction. Results: (1) After 5 days of autologous skin transplantation, the survival rate of autologous skin in patients of artificial dermis group was (95±3)%, similar to (93±3)% in conventional skin grafting group (t=1.262, P>0.05). The results of autologous skin infection of patients in the 2 groups were similar (P>0.05). (2) After autologous skin grafting, the complete healing time of skin grafting area in patients of artificial dermis group was (12.3±2.5) d, similar to (12.7±2.0) d of conventional skin grafting group (t=-0.139, P>0.05). In 3, 6, and 10 months after autologous skin transplantation, the VSS scores of scars in recipient site of patients in artificial dermis group were significantly lower than those of conventional skin grafting group (t=-4.428, -5.655, -6.839, P<0.01). (3) After autologous skin grafting, the complete healing time of donor site in patients of artificial dermis group was obviously shorter than that in conventional skin grafting group (t=-12.435, P<0.01). In 10 months after autologous skin transplantation, the VSS score in donor site of patients in artificial dermis group was significantly lower than that of conventional skin grafting group (t=-16.971, P<0.01). (4) After 12 months of autologous skin transplantation, the functional improvement levels of the functional site of patients in artificial dermis group were good in 4 patients, fair in 15 patients, and bad in 1 patient, while the functional improvement levels of the functional site of patients in conventional skin grafting group were good in 5 patients, fair in 8 patients, and bad in 7 patients. The functional improvement levels of the functional site of patients between the two groups were similar (Z=371.5, P>0.05). Conclusions: Compared with conventional stage Ⅰ functional site scar loosening and transplantation of autologous thin medium-thickness skin, stage Ⅰ functional site scar loosening and artificial dermis implanting+ stage Ⅱ transplantation of autologous split-thickness skin does not affect the survival of skin in the early stage and can effectively improve functional site function, reduce VSS scores of donor site and recipient site, and shorten complete healing time of donor site.

Complications encountered in the treatment of primary and secondary hyperparathyroidism with microwave ablation – a retrospective study

Purpose: To evaluate the complications encountered during microwave ablation (MWA) for primary and secondary hyperparathyroidism (HPT).Materials and methods: The retrospective study enrolled 213 secondary hyperparathyroidism (SHPT) and 51 primary hyperparathyroidism (PHPT) patients who received MWA between July 2015 and September 2018. The major and minor treatment-related complications were documented. The baseline data, clinical parameters, laboratory indices and characteristics of the parathyroid glands were analyzed to assess the risk factors associated with these complications.Results: The incidence of post-MWA complications in HPT patients was 12.1% (32/264). In total, five (5/264, 1.9%) patients with SHPT had major complications, including aphonia/hoarseness (n = 4) and Horner syndrome (n = 1). A total of 27 (10.2%, 27/264) HPT patients had minor complications, including neck hematoma (0.8%, 2/264), bucking (4.2%, 11/264) and phonasthenia (5.3%, 14/264). The incidence of severe hypocalcemia (SH) after MWA was 18.2%. Cutaneous necrosis occurred in two SH patients after intravenous calcium supplementation. There were no significant differences in the incidence of overall complications, major complications and minor complications between SHPT and PHPT patients (12.7% vs 9.8%, p = 0.811; 2.3% vs 0, p = 0.587; 10.3% vs 9.8%, p = 1.000). A history of parathyroidectomy (PTX) (p = 0.031) and multiple symptoms (p = 0.000) were risk factors for the occurrence of complications in SHPT patients. One patient sustained a permanent injury to a unilateral recurrent laryngeal nerve (RLN), and the two patients who experienced cutaneous necrosis underwent debridement plus autologous skin transplantation. The remaining patients recovered without sequelae.Conclusion: The incidence of major complications was low which only occurred in SHPT patients. Most of the patients with complications recovered spontaneously. MWA is safe for the treatment of HPT.

Autologous Free Skin Transplantation to Prevent Esophageal Stricture After Complete Circular Endoscopic Submucosal Dissection for Superficial Esophageal Neoplasms

Introduction: Endoscopic submucosal dissection (ESD) of circumferential superficial esophageal neoplasms (SENs) was associated with extremely high rate of postoperative stricture, which decreases the patient’s quality of life substantially. So far, no standard guideline for preventing esophageal stricture in patients after ESD has been established. We aimed to assess the effectiveness and safety of endoscopic transplantation of autologous free skin in preventing stricture formation after circumferential ESD. Methods: A total of 8 patients who underwent circumferential ESD were included in the study. After undergoing ESD, autologous free skin harvested from the right outer thigh of the patient was sewed into a “oversleeve-like” skin and then covered on the outside of a fully-covered esophageal stent. Finally, the stent was placed at the location of the artificial ulcer of esophagus. The stent was removed 4 weeks after the procedure. The patients were followed up with endoscopy at scheduled times. Results: Complete circular ESD and autologous free skin transplantation were successfully performed in all patients. The mean longitudinal diameter of the resected specimens was 98.8 mm (range 70 - 160 mm). The skin grafts grew well and biopsy-proven squamous epithelium with hyperkeratosis at the site of transplant. Five patients (5 / 8, 62.5 %) didn’t experience dysphagia and stricture with a mean follow-up of 4.9 months (range 3 - 8 months). No complications including perforation, bleeding, wound infection, and stent migration were observed during the follow-up. Conclusion: Endoscopic transplantation of free skin could be a safe and effective way of preventing esophageal stricture after circumferential ESD. Long-term follow-up and experience with a large series are needed to further evaluation of this method.352_A Figure 1. Clinical outcomes for 8 patients with early esophageal cancer after circumferential ESD.352_B Figure 2. ESD resulted in a completely circumferential resection. B, The stent was placed on the esophageal ulcer.352_C Figure 3. At endoscopic follow-up 6 months after ESD, the skin graft grew well without any evidence of stricture. A, C: White-light view. B, D: Iodine stain view.

Development of Individualized Induced Pluripotent Stem Cells From Fibroblasts of Keloid Lesions in Patients

ObjectivePresently, interesting research related to induced pluripotent stem cells (iPSCs) is emerging. However, the development of new therapies and techniques for treatment of refractory diseases is still required in dermatology. We are exploring novel methods to provide stem cell therapy and elucidate research mechanisms underlying troublesome diseases by reprogramming iPSCs from the fibroblasts of keloid lesions from patients in vitro. MethodHere, we identified the expression of fibroblastic genes in the fibroblast derived from diseased individuals. Corresponding iPSCs were then produced by transfecting patient fibroblasts with non-modified RNA cocktails, expressing OCT4, SOX2, KLF4, cMYC, NANOG, and LIN28 reprogramming factors. The pluripotency of these patient-derived iPSCs was identified by immunocytochemistry, real-time quantitative polymerase chain reaction, and teratoma formation in vivo in non-obese diabetic/severe combined immunodeficiency mice. ResultsAll iPSCs derived from patients significantly expressed the pluripotent transcription factors and could be expanded in vitro. Furthermore, induction of terminal differentiation in long-term culture and the capability of forming embryonic bodies to differentiate into all 3 germ layers in vivo were confirmed in immune-deficient mice. ConclusionFibroblasts from a keloid patient were successfully reprogrammed to iPSCs in vitro. This reprogramming may provide a basis for the production of individualized modified artificial skin to prevent rejections after xenogeneic skin transplantation and trauma through autologous skin transplantation. These cells can also offer a new platform for research on mechanisms underlying skin diseases and personal medical applications.

In vitro and in vivo assessment of lactic acid-modified chitosan scaffolds for potential treatment of full-thickness burns.

Autologous skin transplantation is today's "gold standard" treatment for full-thickness burns. However, when > 30% of total body surface area is damaged, there is an important shortage of autologous donor sites for skin grafting; then, treatment alternatives become crucial. Such alternatives can be based on polymeric scaffolds capable of functioning as protective covers and cells/factors carriers. Chitosan (CTS) is a natural-derived polymer with relevant biological-related properties but poor mechanical performance. Improved mechanical properties can be achieved through lactic acid grafting (LA-g); nevertheless, LA-g affects the biological response towards the CTS-based materials. In this work, CTS-LA scaffolds with different LA-g percentages were synthesized and evaluated to determine appropriate LA-g degrees for full-thickness burns treatment. In vitro results indicated that the higher the LA-g percentage, the lower the capability of the scaffolds to sustain fibroblasts culture. Scaffolds with LA-g around 28% (CTS-LA28) sustained cell culture and allowed normal cell functionality. Further evaluation of CTS-LA28 as acellular and cellular grafts in a full-thickness burn mouse model showed that at 28 days post-burn, macroscopic characteristic of the reparation tissue were closer to healthy skin when cellular grafts were used for treatment; histological evaluation also showed that dermis cellularity and collagenous fibers structure were similar to those in healthy skin when cellular grafts were used for burns treatment. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2875-2891, 2017.

The progress and challenges for dermal regeneration in tissue engineering.

Wound healing is an inherent response resulting in the restoration of tissue integrity. It is a complex process involving cell migration, proliferation, differentiation, apoptosis, and the synthesis and remodeling of the extracellular matrix (ECM). The dermal tissue is an important component of skin that acts as a connecting link between the epidermis and hypodermis. The appearance of scars and contractures after autologous split-thickness skin transplantation or single epidermis diaphragm transplantation for full skin defects indicates that the dermal tissue plays an important role in skin regeneration. Theoretically, dermis cannot regenerate like the liver, bone and epidermis after being destroyed by burns or avulsion. Scarring is hard to avoid during the process of natural healing. However, if the dermis could be reconstructed perfectly, this would be a breakthrough in the methods used for wound healing. In this review, we summarize recent research about dermal regeneration and discuss the probability of advances in the field. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1208-1218, 2017.

The use of collagen-based matrices in the treatment of full-thickness wounds

Chronic and complex full-thickness wounds have become increasingly prevalent. Besides autologous skin transplantation, innovative wound dressing products have gained interest, as the functional and esthetic outcome is still limited. In this respect, the effect of a novel modifiable collagen–gelatin fleece on the healing of deep dermal wounds was examined and compared with untreated controls and Matriderm®. A total of 48 full-thickness skin defects were generated on six minipigs and treated with the novel collagen–gelatin fleece of different thicknesses in single or multiple application (n=36) or treated with Matriderm® in a single application (n=6), or the wounds were left untreated (n=6). Wound healing was analyzed planimetrically by wound closure per time and histologically with regard to epidermal thickness and cell density. Compared to untreated wounds, wound closure per time and histological skin quality with regard to the mean epidermal thickness and epidermal cell amount were enhanced in both treatment groups. Overall, the best results for the novel collagen–gelatin fleece were achieved for multiple applications with a thickness of 150g/m2. The novel biomaterial shows accelerated and improved dermal wound repair in a minipig model. As the manufacturing process of the scaffold allows the integration of bioactive substances such as antibiotics and growth factors, we intend to design a composite biomaterial using this scaffold as a carrier matrix.

A Novel Collagen-Gelatin Scaffold for the Treatment of Deep Dermal Wounds—An Evaluation in a Minipig Model

Today, autologous skin transplantation is frequently used for full-thickness skin defects. There is still a high demand for new wound-healing products to replace autologous skin transplantation. In this context, the effect of a new collagen-gelatin scaffold on full-thickness skin defects was evaluated. Four full-thickness skin defects were created surgically on the dorsum of 6 Göttingen minipigs. Three wounds were randomly treated with a novel collagen-gelatin scaffold in different thicknesses, whereas the fourth wound was left untreated and served as a control wound. During the experimental period of 21 days, a close-up photographic documentation was performed. Afterwards, the areas of the initial wounds were excised and examined histologically. The systematic evaluation of 24 wounds showed that treatment with the new collagen-gelatin scaffold led to an accelerated wound repair of 1.1 days. Compared to control wounds, it also demonstrated improved skin quality in regard to epidermal thickness. The new collagen-gelatin scaffold supports and accelerates dermal wound repair compared to untreated control wounds. Nevertheless, wound treatment with the scaffold was only performed on the first day. In further studies, the impact of multiple scaffold applications on full-thickness skin defects should be investigated.