Dermal Regeneration Research Articles

Management of Frontal Bone Exposure Following Paramedian Forehead Flap for Nasal Reconstruction.

The paramedian forehead flap is renowned for its versatility and can cover a wide range of nasal defect sizes. Most of the literature discussing outcomes of paramedian forehead flap reconstructions focuses on morbidity at the recipient site. Frontal bone exposure resulting from the use of the paramedian forehead flap is a rare but possible complication, especially when periosteum overlying the bone is damaged during surgery or during healing by secondary intention due to desiccation. In this case, a 53-year-old female underwent nasal reconstruction with a paramedian forehead flap for an extensive nasal defect after Mohs surgery and resection of residual basal cell carcinoma. She missed her postoperative follow-up visit, and her frontal bone was noted to be exposed before the division of the pedicle procedure. During the division of the pedicle, the frontal bone was burred, and a bilayer dermal regeneration matrix was applied. She underwent a split-thickness skin grafting from her thigh at 4 weeks. The graft take was 100%, and wound closure was achieved with an acceptable cosmetic outcome. The successful resolution of the complication through innovative surgical interventions highlights the importance of adaptive surgical strategies and thorough postoperative care, aiming to contribute to the existing body of knowledge and improve future clinical practices in reconstructive surgery.

From Bank Preparation to Clinical Use of Homologous Skin Allografts in Wound Healing: A Sustainable Approach.

Given progressive population ageing and the increase in the number of patients with comorbidities, the management of chronic and/or hard-to-heal wounds (HHWs) nowadays represents a common problem in many clinical settings. In these cases, standard strategies may not be sufficient. Autologous grafting represent the gold standard for permanent wound closure, but is almost never realized when the skin loss is extensive/the patient is young. The grafting of homologous skin/dermal tissue procured from cadaver donors (i.e., allografting) represents the best alternative, especially when the dermal component is lost. This request supports the activities of skin bank establishments (including donor screening, skin procurement, processing, storage, and distribution) that are regulated by specific guidelines and need to continuously meet quality standard requirements. The aim of this work is to both give specific insights of all the procedures implied in allograft preparation as well as an overview of their practical application in the treatment of different HHWs. The particular characteristics of each skin/dermal allograft released by Siena Skin Bank (cryopreserved/glycerol-preserved skin/de-epidermized dermis, acellular lyophilized de-epidermized dermis/reticular dermis) are also discussed. The exemplificative series of HHWs managed in the Dermatology Department of Siena were classified according their etiology into post-traumatic, vascular (arterial/venous/mixed/lymphatic), inflammatory, surgical, and heat/chemical burns. Globally, the clinical advantages obtained include: acceleration of healing process, pain sparing, resistance to bacterial contamination, dermal regeneration (instead of scarring), and better aesthetic-functional outcome.

Dermal Regeneration Template Generated Skin Can Be Raised as A Flap: A New Dimension in Aesthetic Restoration

AbstractChildhood scars can lead to hideous aesthetic and functional deformities in young adults, which can be particularly distressing when involving the face and the breast in a female. Aesthetic restoration requires replacement of the whole or a part of the scarred skin by soft, pliable, and texture-matching skin, which nearly always is in short supply. Dermal regeneration templates (DRTs) can help in skin regeneration that is almost always aesthetically superior to most flaps. Aesthetic demands at the time of final restoration may require the regenerated skin to be moved as a local flap. As regenerated skin from dermal templates is known to match the vascularity of normal native skin, raising it as a flap should follow logically. This, however, has never been attempted to the best of our knowledge after a thorough literature search. We report a case of successfully using DRT-generated skin raised as a flap for aesthetic reconstruction of a postburn scarred breast in a young female. This adds a whole new dimension to the use of DRTs and points to a new field of research in scar management and aesthetic restoration.

A Review on Dermal Wound Repair and Regeneration Using Antimicrobial-Loaded Microspheres Incorporated into Bovine Collagen Scaffold

In this paper, the developed microsphere-incorporated collagen scaffold presents a promising solution for delivering drugs over wound surfaces in a uniform and sustained manner. The biomaterials utilized in this system are of natural origin, minimizing potential toxicity from core materials, and collagen and gelatin exhibit active wound-healing properties. The collagen scaffold used for the delivery device offers several advantages, including minimizing dressing frequency, facilitating easier examination, and providing added aesthetic value. Furthermore, the protein-based biomaterial scaffold acts as a template for the extracellular matrix in the skin, enhancing the maturation of wounds and enabling the transition to the accelerated production of mature and aligned collagen fibers. The controlled release of antimicrobial drugs through denatured collagens and gelatin microspheres, as well as the efficient healing observed in in vivo studies, demonstrate the potential of this system for effective wound care. Overall, the incorporation of ciprofloxacin-loaded microspheres in porous collagen scaffold offers sustained releases of ciprofloxacin in infected environments, as supported by histological examination showing well-formed epidermis and dermis in the connective tissue of the skin. The system’s ability to heal full-thickness wounds within a significantly shorter time frame compared to antibiotic-incorporated collagen sponges further emphasizes its efficacy in wound healing.

Dermatological rehabilitation in burned children: an integrative review

Introduction: Dermatological rehabilitation in burned children plays a crucial role in restoring skin function and aesthetics after burn injuries. This integrative literature review aims to comprehend the methods and outcomes related to this practice, exploring relevant studies in the field. Methods: To conduct this integrative review, we utilized the PubMed, Scielo, and Virtual Health Library databases. We used specific keywords such as "dermatological rehabilitation," "burned children," and "pediatric burns" to locate relevant articles. Article selection was based on relevance and research quality criteria. Results: This integrative review encompassed various studies related to dermatological rehabilitation in burned children. Some studies focused on negative pressure therapy and its role in the recovery of electric burn injuries. Others explored the use of dermal regeneration matrix in burned patients. Additionally, epidemiological studies were included, providing insights into the profile of burned children treated in hospitals. The review also addressed the importance of physiotherapy in burned patient rehabilitation and factors associated with physical sequelae in burned children. Strategies of kinesiotherapy and the dermatologist's approach in the initial burn care were also discussed. Conclusion: Dermatological rehabilitation in burned children is a multidisciplinary field that requires diverse and individualized approaches. The integrative review highlighted the significance of innovative techniques and treatment strategies to enhance outcomes and the quality of life for burned children. The knowledge gained from these studies can contribute to the improvement of dermatological rehabilitation practices in burned children in the future.

PCL-gelatin honey scaffolds promote Staphylococcus aureus agrA expression in biofilms with Pseudomonas aeruginosa.

Bacterial infection and biofilm formation contribute to impaired healing in chronic diabetic wounds. Staphylococcus aureus and Pseudomonas aeruginosa are found in human diabetic wound biofilms. They may develop antibiotic resistance, increasing the urgency for alternative or complementary therapies. Diabetic wound healing may be improved with the use of biomedically engineered scaffolds, which can also serve as delivery systems for antibacterial compounds. Manuka honey is a potent antibacterial and wound care agent due to its high osmolarity, low pH, and constituents (such as methylglyoxal). Honey exhibits bacteriostatic and bactericidal effects, modulates the expression of biofilm forming genes, and restores antibiotic susceptibility in previously drug resistant pathogens. In this study, we created a dermal regeneration template (DRT) composed of polycaprolactone-gelatin (PCL-gelatin) and Manuka honey to retain honey in the wound and also provide a scaffold for tissue regeneration. Soluble Manuka honey inhibited the planktonic and biofilm growth of both S. aureus (UWH3) and P. aeruginosa (PA14) co-cultures. Manuka honey embedded PCL-gelatin scaffolds did not exhibit bacteriostatic or bactericidal effects on cocultures of UHW3 and PA14; however, they promoted the expression of AgrA, a gene associated with dispersal of S. aureus biofilms.

Use of Integra dermal regeneration template in burn patients: An Italian expert consensus Delphi study

IntroductionBurn injuries pose significant challenges in healthcare, with Integra dermal regeneration template (DRT) emerging as a prominent solution to enhance wound healing and recovery. Although there is no clear consensus on its technical use and application. We convened a panel of 14 burn specialists aiming to provide consensus regarding the application and usage of Integra in managing burn wounds. MethodsPanelists employed a modified Delphi technique to assess agreement and provide feedback on 81 initial statements covering various aspects of Integra DRT application in burn wound care over three subsequent rounds. This study was endorsed by the Italian Society of Burn Surgery (SIUST). ResultsFourteen heads of burn unit departments participated in the Delphi process. At the end of the third round and subsequent discussion on the final statement list, the panel achieved consensus on 24 statements shaping recommendations for Integra application across various aspects, including wound bed preparation, acellular dermal matrix application, definitive coverage, and complication management. ConclusionThe resultant 24 finalized statements from this Italian consensus offer a comprehensive and practical framework for employing Integra DRT in burn patient care. Reflective of specific Italian expertise and practice, these recommendations supplement and refine existing literature, serving as a dynamic guide subject to periodic updates aligned with evolving evidence and experience in the field of burn surgery.

Highly Compressible, Superabsorbent, and Biocompatible Hybrid Cryogel Constructs Comprising Functionalized Chitosan and St. John's Wort Extract.

Biobased porous hydrogels enriched with phytocompounds-rich herbal extracts have aroused great interest in recent years, especially in healthcare. In this study, new macroporous hybrid cryogel constructs comprising thiourea-containing chitosan (CSTU) derivative and a Hypericum perforatum L. extract (HYPE), commonly known as St John's wort, were prepared by a facile one-pot ice-templating strategy. Benefiting from the strong interactions between the functional groups of the CSTU matrix and those of polyphenols in HYPE, the hybrid cryogels possess excellent liquid absorption capacity, mechanical resilience, antioxidant performance, and a broad spectrum of antibacterial activity simultaneously. Thus, owing to their design, the hybrid constructs exhibit an interconnected porous architecture with the ability to absorb over 33 and 136 times their dry weight, respectively, when contacted with a phosphate buffer solution (pH 7.4) and an acidic aqueous solution (pH 2). These cryogel constructs have extremely high compressive strengths ranging from 839 to 1045 kPa and withstand elevated strains of over 70% without developing fractures. Moreover, the water-swollen hybrid cryogels with the highest HYPE content revealed a complete and instant shape recovery after uniaxial compression. The incorporation of HYPE into CSTU cryogels enabled substantial improvement in scavenging reactive oxygen species and an expanded antibacterial spectrum toward multiple pathogens, including Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungi (Candida albicans). Cell viability experiments demonstrated the cytocompatibility of the 3D cryogel constructs, which did not induce changes in the fibroblast morphology. This work showcases a simple and effective strategy to immobilize HYPE extracts on CSTU 3D networks, allowing the development of novel multifunctional platforms with promising potential in hemostasis, wound dressing, and dermal regeneration scaffolds.

Lower Limb Elephnatiasis Nostras Verrucosa: Excision with full thickness skin grafting with aid of dermal regeneration template

Elephnatiasis Nostras Verrucosa (ENV) is a rare clinical condition, a progressively disfiguring disorder characterized by verrucous, nodules and cobblestone-like papules associated with non-pitting edema of the lower extremities. Histopathology is characterized by epidermal hyperkeratosis and dermal fibrosis. We report the history of a 32-year-old man who presented with 5 years history of right lower limb edema covered by nodular and papular skin lesions. Proper investigations put the diagnosis of ENV. The patient was successfully treated by debridement followed by skin graft using the technique of dermal regeneration. Management of ENV remains challenging. In the absence of randomized controlled trials on the best modalities of treatment, it is important to report such rare cases and their treatment outcome.

Tropoelastin modulates systemic and local tissue responses to enhance wound healing

Wound healing is facilitated by biomaterials-based grafts and substantially impacted by orchestrated inflammatory responses that are essential to the normal repair process. Tropoelastin (TE) based materials are known to shorten the period for wound repair but the mechanism of anti-inflammatory performance is not known. To explore this, we compared the performance of the gold standard Integra Dermal Regeneration Template (Integra), polyglycerol sebacate (PGS), and TE blended with PGS, in a murine full-thickness cutaneous wound healing study. Systemically, blending with TE favorably increased the F4/80+ macrophage population by day 7 in the spleen and contemporaneously induced elevated plasma levels of anti-inflammatory IL-10. In contrast, the PGS graft without TE prompted prolonged inflammation, as evidenced by splenomegaly and greater splenic granulocyte and monocyte fractions at day 14. Locally, the inclusion of TE in the graft led to increased anti-inflammatory M2 macrophages and CD4+T cells at the wound site, and a rise in Foxp3+ regulatory T cells in the wound bed by day 7. We conclude that the TE-incorporated skin graft delivers a pro-healing environment by modulating systemic and local tissue responses. Statement of significanceTropoelastin (TE) has shown significant benefits in promoting the repair and regeneration of damaged human tissues. In this study, we show that TE promotes an anti-inflammatory environment that facilitates cutaneous wound healing. In a mouse model, we find that inserting a TE-containing material into a full-thickness wound results in defined, pro-healing local and systemic tissue responses. These findings advance our understanding of TE's restorative value in tissue engineering and regenerative medicine, and pave the way for clinical applications.

An ADSC-loaded dermal regeneration template promotes full-thickness wound healing

IntroductionFull-thickness wounds lead to delayed wound healing and scarring. Adipose-derived stem cell (ADSC) grafting promotes wound healing and minimizes scarring, but the low efficiency of grafting has been a challenge. We hypothesized that loading ADSCs onto a clinically widely used dermal regeneration template (DRT) would improve the efficacy of ADSC grafting and promote full-thickness wound healing. MethodsADSCs from human adipose tissue were isolated, expanded, and labeled with a cell tracker. Labeled ADSCs were loaded onto the DRT. The viability, the location of ADSCs on the DRT, and the abundance of ADSCs in the wound area were confirmed using CCK8 and fluorescence microscopy. Full-thickness wounds were created on Bama minipigs, which were applied with sham, ADSC, DRT, and ADSC-DRT. Wounds from the four groups were collected at the indicated time and histological analysis was performed. RNA-seq analysis was also conducted to identify transcriptional differences among the four groups. The identified genes by RNA-seq were verified by qPCR. Immunohistochemistry and western blotting were used to assess collagen deposition. In vitro, the supernatant of ADSCs was used to culture fibroblasts to investigate the effect of ADSCs on fibroblast transformation into myofibroblasts. ResultsADSCs were successfully isolated, marked, and loaded onto the DRT. The abundance of ADSCs in the wound area was significantly greater in the ADSC-DRT group than in the ADSC group. Moreover, the ADSC-DRT group exhibited better wound healing with improved re-epithelialization and denser collagen deposition than the other three groups. The RNA-seq results suggested that the application of the integrated ADSC-DRT system resulted in the differential expression of genes mainly associated with extracellular matrix remodeling. In vivo, wounds from the ADSC-DRT group exhibited an earlier increase in type III collagen deposition and alleviated scar formation. ADSCs inhibited the transformation of fibroblasts into myofibroblasts, along with increased levels of CTGF, FGF, and HGF in the supernatant of ADSCs. Wounds from the ADSC-DRT group had up-regulated expressions of CTGF, HGF, FGF, and MMP3. ConclusionThe integral of ADSC-DRT increased the efficacy of ADSC grafting, and promoted full-thickness wound healing with better extracellular matrix remodeling and alleviated scar formation.

Case Report ‘Layer of Hope’: Managing Large Surface Wounds on Frontal Bare Bone in a Challenging Patient

This was a case of an elderly gentleman with large bleeding basal cell carcinoma occupying almost three quarter of the forehead managed with adjunct usage of integra acellular dermal regeneration template after lesion’s wide local excision despite challenged with patient’s newly diagnosed bicytopenia to rule out haematological malignancy. Standard management of tissue reconstruction with purely living tissue (split skin grafting) has higher risk of graft rejection due to bare bone as wound bed. This limits the neo-graft ability to achieve optimal potential of imbibition and inosculation. Thus, dermal matrix usage makes split skin grafting difficult wound bed has higher chance of surviving and hence shortens healing time and reduces hospital stay.

Letter to the editor "Early identification of delayed wound healing in complex diabetic foot ulcers treated with a dermal regeneration template: a novel clinical target and its risk factors".

Letter to the editor "Early identification of delayed wound healing in complex diabetic foot ulcers treated with a dermal regeneration template: a novel clinical target and its risk factors".

A Two-Step Approach to the Surgical Treatment of Soft-Tissue Sarcomas.

Background: Nowadays, limb-sparing procedures are the gold standard in the treatment of soft-tissue sarcomas of the limbs. Wide tumor resection with appropriate oncological margins, reconstruction, and stabilization of the involved bone and joint and restoration of the soft tissue lost are essential in order to obtain good clinical and functional outcomes. Tumor excision and soft-tissue reconstruction performed in one-step surgery is chosen by many centers as the preferred approach; however, according to our experience in some selected patients, two-step surgery performed using a dermal regeneration template first and then a margin revision, taking into account the definitive results of the anatomopathological exam conducted over the surgical specimen from the previous surgery, associated with definitive reconstruction surgery over a healthy bed of granulated tissue, showed many potential benefits. Methods: A retrospective observational study was conducted on thirteen patients who underwent a two-step reconstruction procedure using dermal substitution after soft-tissue sarcoma excision. Results: Clinically, the enrolled patients achieved excellent contour and cosmesis of their surgical wounds, with a mean VSS value of 3.07. During the follow-up period, no local recurrences were observed in any patient. Conclusions: Two-step surgery represents the most suitable solution to allow surgical radicality with minimal recurrency and adequate soft-tissue reconstruction, avoiding the possibility of wasting autologous tissue. Our patients generally embraced this approach and the management that followed.

D57. A Single Center 13-year Experience with a 3-stage Dermal Regeneration Matrix Approach to the Acute Management of Hand Burns

D57. A Single Center 13-year Experience with a 3-stage Dermal Regeneration Matrix Approach to the Acute Management of Hand Burns

New Regenerative and Anti-Aging Medicine Approach Based on Single-Stranded Alpha-1 Collagen for Neo-Collagenesis Induction: Clinical and Instrumental Experience of a New Injective Polycomponent Formulation for Dermal Regeneration.

This study explores the efficacy of a novel polycomponent formulation (KARISMA Rh Collagen® FACE, Taumedika Srl, Rome, Italy), containing 200 mg/mL of non-crosslinked high-molecular-weight hyaluronic acid (HMW-HA), 200 μg/mL of a human recombinant polypeptide of collagen-1 alpha chain, and 40 mg/mL of carboxymethyl cellulose (CMC) as a regenerative medicine for skin regeneration and rejuvenation. This formulation combines non-crosslinked high-molecular-weight hyaluronic acid, human recombinant polypeptide of collagen-1 alpha chain, and carboxymethyl cellulose to stimulate collagen type I production and enhance skin hydration. This study involved 100 subjects with varying skin conditions, divided into three groups based on skin aging, smoking history, and facial scarring, to evaluate the product's effectiveness in skin regeneration and aesthetic improvement. The methodology included two injections of Karisma (2 mL for each injection) one month apart, with evaluations conducted using FACE-Q questionnaires, the SGAIS Questionnaire, and Antera 3D skin scanner measurements at baseline, 30 days, and 60 days post-treatment. The results demonstrated a significant reduction in skin roughness and an improvement in skin quality across all the groups, with no correlation between the outcomes and the patient's age. The subjective assessments also indicated high satisfaction with the treatment's aesthetic results. The analyzed data allow us to conclude that the single-stranded collagen with hyaluronic acid and carboxymethyl-cellulose formulation is able to stimulate the skin's regenerative response, yielding significant results both in vitro and, through our study, also in vivo. This new polycomponent formulation effectively stimulates skin regeneration, improving skin quality and texture, with significant aesthetic benefits perceived by patients, and a low incidence of adverse events, marking a promising advancement in regenerative medicine.

787 A 13-year Experience with a 3-stage Dermal Regeneration Matrix Approach to Acute Hand Burns

787 A 13-year Experience with a 3-stage Dermal Regeneration Matrix Approach to Acute Hand Burns

The Goettingen minipig as an experimental model in wound-healing studies

BackgroundDeep dermal wounds in extensive burns and chronic wound-healing disorders represent a significant medical problem and require a high level of therapy to reduce the risk of infection and other long-term consequences, such as amputation. A better understanding of the wound-healing processes is essential, and animal models are indispensable to fundamental research. ObjectiveThis study aimed to provide a transparent protocol and prove the effectiveness of an in vivo porcine model using Goettingen minipigs for wound-healing studies. Material and methodsThirteen female Goettingen minipigs were kept in species-appropriate housing and were treated according to the German law for the protection of animals. The study was performed with permission from the local ethical review committee of animal welfare. The experimental procedure for studying dermal regeneration in 102 full-thickness wounds through clinical observation and histological analysis, focusing on neodermal formation, is described in detail. ResultsThe Goettingen minipig model proved to be suitable in wound-healing studies. The dermal regeneration was evident and viewable without wound contamination or any rejection reaction. The histological evaluations were also reliable and clearly presented the optimized wound healing of deep dermal wounds using the different therapeutic approaches. ConclusionGiven the great clinical need for alternative or complementary therapies, we considered the Goettingen minipig trial a reliable, ethically justifiable, effective, and reproducible in vivo model for wound-healing studies.

Early identification of delayed wound healing in complex diabetic foot ulcers treated with a dermal regeneration template: a novel clinical target and its risk factors: Erratum.

Early identification of delayed wound healing in complex diabetic foot ulcers treated with a dermal regeneration template: a novel clinical target and its risk factors: Erratum.

The use of bone wax versus dermal regeneration matrix for the reconstruction of scalp defects.

Secondary intention healing is an alternative to consider in large tumors or tumors located in areas of limited skin mobility, such as the scalp. To promote epithelialization, we can use Dermal Regeneration Matrix (DRM) or bone wax. This study aimed to compare the efficacy of DRM and bone wax in secondary intention healing of cutaneous scalp tumors in elderly patients with comorbidities. The medical records of 18 patients with cutaneous scalp tumor healing by secondary intention from February 2022 to April 2023 were analyzed for demographic variables, tumor and surgical characteristics, time from withdrawal of material to complete epithelialization, and need for subsequent surgical intervention. Bone wax was used in 6 patients and DRM in 12. The mean patient age was 84.3 years, and the mean tumor size was 2.7 cm. There were no significant differences in demographics or postoperative complications between the groups. The median time to complete epithelization was 84.5 (60.2-108.7) days in the bone wax group and 105.0 (91.0-126.0) days in the DRM group, with no significant differences (P = 0.15). Bone wax is a simple and economical material that can be used for secondary intention healing of scalp tumors in elderly patients with high surgical risk.