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Current Challenges and Advances in Skin Repair and Regeneration

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Plastic, Reconstructive and Aesthetic Surgery/Aesthetic Medicine".

Deadline for manuscript submissions: closed (25 February 2023) | Viewed by 23034

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Special Issue Editor

Dr. Giovanni Salzano

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Guest Editor

Maxillofacial Surgery Operative Unit, University Hospital of Naples "Federico II", 80131 Naples, Italy
Interests: oral and maxillofacial surgery; plastic surgery; otolaryngology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The skin is a complex structure composed of the epidermis, dermis, and subcutaneous fat, acting as a barrier against the penetration of damaging UV rays from the sun, the invasion of harmful pathogens, and the evaporation of water, thereby protecting the underlying organs. In clinical practice, we are required to address the interruption of skin integrity by different external factors which range from an iatrogenic or post-traumatic excision to a severe loss of tissue, such as in relation to an ulcer, or even to an alteration of the skin structure by chemicals or heat. These alterations can lead to an altered function of this complex organ.

In the last few years, we have observed an increased interest in skin repair and regeneration in order to improve the positive results achievable with autologous grafts, either with full or partial thickness. Today, we can observe an intense focus on dermal substitutes. There are many reports in the literature of cases where these substitutes have been able to improve the wound-healing process, playing a role in the control of scarring, particularly in relation to patients where in the past, a dermal loss would have implied the need for a full-thickness skin graft with a great scar retraction. Recently, innovative research studies have proposed the application of mesenchymal stem-cell-derived exosomes and nano-sized vesicles able to induce strong anti-inflammatory, anti-aging, and wound-healing effects, thereby easing the regenerative process.

Dr. Giovanni Salzano
Guest Editor

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Keywords

skin repair
skin regeneration
dermal substitute
burn injuries
skin defects
autologous graft
post-traumatic injuries
chemical injury

Published Papers (10 papers)

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Research

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14 pages, 1359 KiB

Open AccessArticle

The Impact of Antiseptic-Loaded Bacterial Nanocellulose on Different Biofilms—An Effective Treatment for Chronic Wounds?

by Hanna Luze, Ives Bernardelli de Mattos, Sebastian Philipp Nischwitz, Martin Funk, Alexandru Cristian Tuca and Lars-Peter Kamolz

J. Clin. Med. 2022, 11(22), 6634; https://doi.org/10.3390/jcm11226634 - 9 Nov 2022

Cited by 1 | Viewed by 1479

Abstract

Introduction: Pathogenic biofilms are an important factor for impaired wound healing, subsequently leading to chronic wounds. Nonsurgical treatment of chronic wound infections is limited to the use of conventional systemic antibiotics and antiseptics. Wound dressings based on bacterial nanocellulose (BNC) are considered a promising approach as an effective carrier for antiseptics. The aim of the present study was to investigate the antimicrobial activity of antiseptic-loaded BNC against in vitro biofilms. Materials and Methods: BNC was loaded with the commercially available antiseptics Prontosan^® and Octenisept^®. The silver-based dressing Aquacel^®Ag Extra was used as a positive control. The biofilm efficacy of the loaded BNC sheets was tested against an in vitro 24-hour biofilm of Staphylococcus aureus and Candida albicans and a 48-hour biofilm of Pseudomonas aeruginosa. In vivo tests using a porcine excisional wound model was used to analyze the effect of a prolonged treatment with the antiseptics on the healing process. Results: We observed complete eradication of S. aureus biofilm in BNC loaded with Octenisept^® and C. albicans biofilm for BNC loaded with Octenisept^® or Prontosan^®. Treatment with unloaded BNC also resulted in a statistically significant reduction in bacterial cell density of S. aureus compared to untreated biofilm. No difference on the wound healing outcome was observed for the wounds treated for seven days using BNC alone in comparison to BNC combined with Prontosan^® or with Octenisept^®. Conclusions: Based on these results, antiseptic-loaded BNC represents a promising and effective approach for the treatment of biofilms. Additionally, the prolonged exposure to the antiseptics does not affect the healing outcome. Prevention and treatment of chronic wound infections may be feasible with this novel approach and may even be superior to existing modalities. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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12 pages, 4156 KiB

Open AccessArticle

Histopathological Evaluation of the Healing Process of Standardized Skin Burns in Rabbits: Assessment of a Natural Product with Honey and Essential Oils

by Anis Anis, Ahmed Sharshar, Saber El Hanbally and Awad A. Shehata

J. Clin. Med. 2022, 11(21), 6417; https://doi.org/10.3390/jcm11216417 - 29 Oct 2022

Cited by 1 | Viewed by 3368

Abstract

Skin burns are one of the most difficult medical problems. Recently, studies have been directed towards development of natural products in order to identify effective and safe remedies. In the present study, we evaluated the efficacy of a natural composite (formulated from honey and essential oils) compared with MEBO^® (0.25% β-sitosterol) and DERMAZIN^® creams (1% silver-sulfadiazine) in the treatment of thermally induced skin burns. For this purpose, four burn-wounds were created on the back of male New Zealand rabbits (n = 10) using a thermal stamp under the effect of general anesthesia. Each wound represents one of the following groups: non-treated, natural composite-cream, MEBO^®-cream, and silver-sulfadiazine treated groups, respectively. Treatments were applied once a day topically until one of these wounds appeared to be healed grossly. The non-treated group received no treatment. Grossly, skin burns have been healed after 28 days of the treatment in all groups except of the non-treated group. The healing efficacy of the natural composite, MEBO^® and silver-sulfadiazine creams was quite similar macroscopically. However, microscopically, the epidermal layer of the composite-cream treated group was more mature than those of both MEBO^® and silver-sulfadiazine creams treated groups. In conclusion, the tested composite may be a promising effective and inexpensive treatment of skin burns. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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7 pages, 6664 KiB

Open AccessArticle

Three Different Types of Fat Grafting for Facial Systemic Sclerosis: A Case Series

by Antonio Arena, Umberto Committeri, Fabio Maglitto, Giovanni Salzano, Giovanni Dell’Aversana Orabona, Luigi Angelo Vaira, Pasquale Piombino, Michela Apolito, Gianluca Renato De Fazio and Luigi Califano

J. Clin. Med. 2022, 11(18), 5489; https://doi.org/10.3390/jcm11185489 - 19 Sep 2022

Cited by 2 | Viewed by 1934

Abstract

Systemic sclerosis (SSc) is a heterogeneous, chronic connective tissue disease, characterized by skin fibrosis as well as vascular and visceral lesions. It can involve the lungs, heart, kidneys, gastrointestinal tract, and bones. The orofacial manifestations of SSc can cause functional, aesthetic, and social distress, resulting in significant psychological implications for the patients. In recent decades, fat grafting improved the aesthetic outcomes in terms of volume deficiency, contour asymmetry, and skin elasticity of the face thanks to the regenerative action of the stem cells contained within it. We describe five cases of a patient with SSc treated with fat grafting used to correct volume loss and facial elasticity of the lips and perioral region on the middle and lower third of the face. All the patients received regular postoperative checks at weeks 1 and 2. A multiple choice questionnaire was administered to assess the degree of tolerability of the procedure. The reliability of the questionnaire was evaluated by calculating the Cronbach alpha using the MedCalc Statistical Software version 20.113. The aim of our study is to describe three different types of fat grafting used to correct volume loss and restore facial elasticity of the lips and perioral region on the middle and lower third of the face. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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11 pages, 2187 KiB

Open AccessArticle

Preliminary Single-Center Experience of Bromelain-Based Eschar Removal in Children with Mixed Deep Dermal and Full Thickness Burns

by Tomasz Korzeniowski, Ewelina Grywalska, Jerzy Strużyna, Magdalena Bugaj-Tobiasz, Agnieszka Surowiecka, Izabela Korona-Głowniak, Magdalena Staśkiewicz and Kamil Torres

J. Clin. Med. 2022, 11(16), 4800; https://doi.org/10.3390/jcm11164800 - 17 Aug 2022

Cited by 5 | Viewed by 1487

Abstract

Introduction: Early eschar removal is the standard management of burns. The goal is to remove all of the necrotic tissue and render the wound suitable for healing or skin grafting. The enzymatic debridement of burn wounds allows for minimally invasive removal of burn eschar. The aim of the study was to describe and compare the demographic characteristics, surgical treatment and outcomes of patients treated with Nexobrid^® with patients who had standard surgical excision. Material and Methods: A retrospective review was conducted on children who underwent enzymatic debridement. The study group was compared with children treated with the standard of care (SoC). Results: Twelve children (mean age 8 years, range 3 to 15 years) with mixed deep dermal and full thickness burn wounds were treated with Nexobrid^®. The mean size of the burns was 29% TBSA. The median percentage TBSA debrided using Nexobrid^® was 15% (range 2–27%). In a clinical assessment, enzymatic debridement was effective in removing dead tissue in a single application. No adverse reaction to Nexobrid^® and serious complications after enzymatic procedure were recorded in the study group. The estimated relative risk of the need for reconstructive procedures decreases 3.5 times for the study group (RR 3.5, 95%CI 0.9–13.5, p = 0.089). Conclusion: The bromelain-based enzymatic method offers a good and safe debridement option to improve the treatment and life quality of children with severe burns. The main outcome of interest was the number of reconstructive procedures due to scar contractures, which was reduced in the group treated enzymatically compared to the SoC-treated children. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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12 pages, 2120 KiB

Open AccessArticle

Objective Skin Quality Assessment after Reconstructive Procedures for Facial Skin Defects

by Dinko Martinovic, Slaven Lupi-Ferandin, Daria Tokic, Mislav Usljebrka, Andrija Rados, Ante Pojatina, Sanja Kadic, Ema Puizina, Ante Mihovilovic, Marko Kumric, Marino Vilovic, Dario Leskur and Josko Bozic

J. Clin. Med. 2022, 11(15), 4471; https://doi.org/10.3390/jcm11154471 - 31 Jul 2022

Cited by 4 | Viewed by 1323

Abstract

Local random skin flaps and skin grafts are everyday surgical techniques used to reconstruct skin defects. Although their clinical advantages and disadvantages are well known, there are still uncertainties with respect to their long-term results. Hence, the aim of this study was to evaluate outcomes more than one-year post operatively using objective measurement devices. The study included 31 facial defects reconstructed with local random flap, 30 facial defects reconstructed with split-thickness skin grafts (STSGs) and 30 facial defects reconstructed with full-thickness skin grafts (FTSGs). Skin quality was objectively evaluated using MP6 noninvasive probes (Courage + Khazaka GmbH, Cologne, Germany), which measure melanin count, erythema, hydration, sebum, friction and transepidermal water loss. The results showed that there were no significant differences in melanin count, erythema, hydration, sebum level, friction value and transepidermal water loss (TEWL) between the site reconstructed with random local flaps and the same site on the healthy contralateral side of the face. However, both FTSGs and STSGs showed significantly higher levels in terms of TEWL and erythema, whereas the levels of hydration, sebum and friction were significantly lower compared to the healthy contralateral side. Moreover, STSGs resulted in a significant difference in melanin count. These findings imply that the complex pathophysiology of the wound-healing process possibly results in better skin-quality outcomes for random local flaps than skin autografts. Consequently, this suggests that random local flaps should be implemented whenever possible for the reconstruction of facial region defects. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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11 pages, 2178 KiB

Open AccessArticle

Modified Mini-Keystone Flaps for Coverage of Tiny Volar Pulp Defects of the Fingertips in Cases with Missing Amputation Skin Stumps: A Retrospective Study

by Byung Woo Yoo, Seungyoon Oh, Junekyu Kim, Kap Sung Oh, Hyun Woo Shin and Kyu Nam Kim

J. Clin. Med. 2022, 11(12), 3394; https://doi.org/10.3390/jcm11123394 - 13 Jun 2022

Viewed by 1866

Abstract

This study aimed to demonstrate the expanding versatility of keystone flap reconstruction in fingertips. Fifteen patients who underwent the modified mini-keystone flap reconstruction for tiny volar pulp defects of the fingertip between September 2020 and February 2021 were included in this study (average age: 43.4 ± 13.52 years, range: 19–61 years). Patient data were retrospectively collected from their medical records. The two-point discrimination test was used to evaluate the degree of sensory recovery. All defects were successfully covered with the modified mini-keystone flap. The defect sizes ranged from 0.5 cm × 1 cm to 1.2 cm × 2.0 cm, and the flap sizes ranged from 0.7 cm × 1.5 cm to 1.5 cm × 3.0 cm. Although one patient showed a small distal margin maceration, all flaps survived fully. The overall outcomes were favorable at the mean follow-up period of 5.73 ± 0.79 months. We suggest that the modified mini-keystone flap technique is a promising alternative modality for covering tiny volar pulp defects of the fingertip, with few complications and favorable outcomes. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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11 pages, 999 KiB

Open AccessArticle

Clinical Evaluation of the Efficacy and Tolerability of Rigenase^® and Polyhexanide (Fitostimoline^® Plus) vs. Hyaluronic Acid and Silver Sulfadiazine (Connettivina^® Bio Plus) for the Treatment of Acute Skin Wounds: A Randomized Trial

by Raffaele Russo, Albino Carrizzo, Alfonso Barbato, Barbara Rosa Rasile, Paola Pentangelo, Alessandra Ceccaroni, Caterina Marra, Carmine Alfano and Luigi Losco

J. Clin. Med. 2022, 11(9), 2518; https://doi.org/10.3390/jcm11092518 - 29 Apr 2022

Cited by 7 | Viewed by 2046

Abstract

Objectives: Compare the efficacy and tolerability of Connettivina^® Bio Plus (Group A) gauze and cream, and Fitostimoline^® Plus (Group B) gauze and cream for the treatment of acute superficial skin lesions. Design: Single-center, parallel, randomized trial. A block randomization method was used. Setting: University of Salerno—AOU San Giovanni di Dio e Ruggi d’Aragona. Participants: Sixty patients were enrolled. All patients fulfilled the study requirements. Intervention: One application of the study drugs every 24 h, and a six-week observation period. Main outcome measures: Efficacy and tolerability of the study drugs. Results: In total, 60 patients (Group A, n = 30; Group B, n = 30) were randomized; mean age was 58.5 ± 15.8 years. All patients were included in the outcome analysis. Total wound healing was achieved in 17 patients undergoing treatment with Connettivina^® Bio Plus and 28 patients undergoing treatment with Fitostimoline^® Plus. The greater effectiveness of the latter was significant (p = 0.00104). In Group B, a significantly greater degree of effectiveness was observed in reducing the fibrin in the wound bed (p = 0.04746). Complications or unexpected events were not observed. Conclusions: Both Connettivina^® Bio Plus and Fitostimoline^® Plus are secure and effective for treating acute superficial skin lesions. Fitostimoline^® Plus was more effective than Connettivina^® Bio Plus in wound healing of acute superficial skin lesions, especially if fibrin had been observed in the wound bed. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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11 pages, 2096 KiB

Open AccessArticle

A Prospective Randomized Controlled Multicenter Clinical Trial Comparing Paste-Type Acellular Dermal Matrix to Standard Care for the Treatment of Chronic Wounds

by Youn Hwan Kim, Hyung Sup Shim, Jihye Lee and Sang Wha Kim

J. Clin. Med. 2022, 11(8), 2203; https://doi.org/10.3390/jcm11082203 - 14 Apr 2022

Cited by 4 | Viewed by 1851

Abstract

The treatment of chronic wounds remains challenging. Acellular dermal matrix (ADM) has been shown to be effective for various types of wound healing. This study was designed to compare the wound size reduction rate after 12 weeks between patients receiving paste-type ADM and standard wound care. Patients over 19 years old with chronic wounds, deeper than full-thickness skin defects, more than 4 cm² in size that did not heal over the 3 weeks before the study were included. After a screening period of 7 days, patients were randomized to receive either paste-type ADM or standard wound care. The wound status was evaluated at baseline, 1, 2, 4, 8, and 12 weeks. A total of 86 patients were enrolled in this study. The wounds continuously and constantly reduced in size from week 1, and the reduction rate was significantly greater in the study group from week 2 until the end (week 12). In the study group, wound healing was achieved in 29 of 38 wounds (76.3%). Paste-type ADM might be a useful option for wound healing and can be applied safely and efficiently for advanced wound care. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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Review

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13 pages, 6945 KiB

Open AccessReview

Locoregional Flaps for the Reconstruction of Midface Skin Defects: A Collection of Key Surgical Techniques

by Giovanni Salzano, Francesco Maffìa, Luigi Angelo Vaira, Umberto Committeri, Chiara Copelli, Fabio Maglitto, Alfonso Manfuso, Vincenzo Abbate, Paola Bonavolontà, Alfonso Scarpa, Luigi Califano and Giovanni Dell’Aversana Orabona

J. Clin. Med. 2023, 12(11), 3700; https://doi.org/10.3390/jcm12113700 - 26 May 2023

Cited by 1 | Viewed by 3526

Abstract

Background: The reconstruction of midface skin defects represents a challenge for the head and neck surgeon due to the midface’s significant role in defining important facial traits. Due to the high complexity of the midface region, there is no possibility to use one definitive flap for all purposes. For moderate defects, the most common reconstructive techniques are represented by regional flaps. These flaps can be defined as donor tissue with a pedunculated axial blood supply not necessarily adjacent to the defect. The aim of this study is to highlight the more common surgical techniques adopted for midface reconstruction, providing a focus on each technique with its description and indications. Methods: A literature review was conducted using PubMed, an international database. The target of the research was to collect at least 10 different surgical techniques. Results: Twelve different techniques were selected and cataloged. The flaps included were the bilobed flap, rhomboid flap, facial-artery-based flaps (nasolabial flap, island composite nasal flap, retroangular flap), cervicofacial flap, paramedian forehead flap, frontal hairline island flap, keystone flap, Karapandzic flap, Abbè flap, and Mustardè flap. Conclusions: The study of the facial subunits, the location and size of the defect, the choice of the appropriate flap, and respect for the vascular pedicles are the key elements for optimal outcomes. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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14 pages, 2015 KiB

Open AccessReview

The Role of the Immune System in Pediatric Burns: A Systematic Review

by Tomasz Korzeniowski, Paulina Mertowska, Sebastian Mertowski, Martyna Podgajna, Ewelina Grywalska, Jerzy Strużyna and Kamil Torres

J. Clin. Med. 2022, 11(8), 2262; https://doi.org/10.3390/jcm11082262 - 18 Apr 2022

Cited by 6 | Viewed by 2639

Abstract

Burns are one of the most common causes of home injuries, characterized by serious damage to the skin and causing the death of affected tissues. In this review, we intended to collect information on the pathophysiological effects of burns in pediatric patients, with particular emphasis on local and systemic responses. A total of 92 articles were included in the review, and the time range of the searched articles was from 2000 to 2021. The occurrence of thermal injuries is a problem that requires special attention in pediatric patients who are still developing. Their exposure to various burns may cause disturbances in the immune response, not only in the area of tissue damage itself but also by disrupting the systemic immune response. The aspect of immunological mechanisms in burns requires further research, and in particular, it is important to focus on younger patients as the existence of subtle differences in wound healing between adults and children may significantly influence the treatment of pediatric patients. Full article

(This article belongs to the Special Issue Current Challenges and Advances in Skin Repair and Regeneration)

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