Treatment of a Congenital Melocytic Giant Naevi at Age 39 Using Split-Thickness Skin Graft Over an Artificial Dermal Scaffold Through 2-Step Operation: A Novel Technique and Literature Review.

Congenital melanocytic nevus is a benign proliferation seen from birth. However, malignant transformation can be observed in later ages, so the removal of especially large and giant nevi is recommended during childhood. Nevertheless, there are no cases reported in the literature regarding excision of giant congenital melanocytic nevi in advanced age. This article presents the first case of a 39-year-old patient with a giant congenital melanocytic nevus covering 10% of the total body surface area, who underwent treatment with a 2-step operation. The nevus was located on the back, covering 10% of the total body surface area. The patient underwent en-bloc excision. A bilayer dermal matrix was applied over the fascia. Subsequently, a split-thickness skin graft was applied to the entire area. Full re-epithelialization was achieved within a total of 35 days. Thanks to the applied dermal scaffold, the area became pliable.

Enhancing diabetic wound healing through anti-bacterial and promoting angiogenesis using dual-functional slow-release microspheres-loaded dermal scaffolds.

Bacterial infections and the degeneration of the capillary network comprise the primary factors that contribute to the delayed healing of diabetic wounds. However, treatment modalities that cater to effective diabetic wounds healing in clinical settings are severely lacking. Herein, a dual-functional microsphere carrier was designed, which encapsulates polyhexamethylene biguanide (PHMB) or recombinant human vascular endothelial growth factor (rhVEGF) together. The in vitro release experiments demonstrated that the use of the microspheres ensured the sustained release of the drugs (PHMB or rhVEGF) over a period of 12 days. Additionally, the integration of these controlled-release microspheres into a dermal scaffold (DS-PLGA@PHMB/rhVEGF) imbued both antibacterial and angiogenic functions to the resulting material. Accordingly, the DS-PLGA@PHMB/rhVEGF scaffold exhibited potent antibacterial properties, effectively suppressing bacterial growth and providing a conducive environment for wound healing, thereby addressing the drawbacks associated with the susceptibility of rhVEGF to deactivation in inflammatory conditions. Additionally, the histological analysis revealed that the use of the DS-PLGA@PHMB/rhVEGF scaffold accelerated the process of wound healing by inhibiting inflammatory reactions, stimulating the production of collagen formation, and enhancing angiogenesis. This provides a novel solution for enhancing the antibacterial and vascularization capabilities of artificial dermal scaffolds, providing a beacon of hope for improving diabetic wound healing.

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.

Optical coherence tomography for in vivo longitudinal monitoring of artificial dermal scaffold.

OBJECTIVES: Artificial dermal scaffold (ADS) has undergone rapid development and been increasingly used for treating skin wound in clinics due to its good biocompatibility, controllable degradation, and low risk of disease infection. To obtain good treatment efficacy, ADS needs to be monitored longitudinally during the treatment process. For example, scaffold-tissue fit, cell in-growth, vascular regeneration, and scaffold degradation are the key properties to be inspected. However, to date, there are no effective, real-time, and noninvasive techniques to meet the requirement of the scaffold monitoring above. MATERIALS AND METHODS: In this study, we propose to use optical coherence tomography (OCT) to monitor ADS in vivo through three-dimensional imaging. A swept source OCT system with a handheld probe was developed for in vivo skin imaging. Moreover, a cell in-growth, vascular regeneration, and scaffold degradation rate (IRDR) was defined with the volume reduction rate of the scaffold's collagen sponge layer. To measure the IRDR, a semiautomatic image segmentation algorithm was designed based on U-Net to segment the collagen sponge layer of the scaffold from OCT images. RESULTS: The results show that the scaffold-tissue fit can be clearly visualized under OCT imaging. The IRDR can be computed based on the volume of the segmented collagen sponge layer. It is observed that the IRDR appeared to a linear function of the time and in addition, the IRDR varied among different skin parts. CONCLUSION: Overall, it can be concluded that OCT has a good potential to monitor ADS in vivo. This can help guide the clinicians to control the treatment with ADS to improve the therapy.

Evaluating the Biocompatibility of an Injectable Wound Matrix in a Murine Model.

(1) Background: Developing a high-quality, injectable biomaterial that is labor-saving, cost-efficient, and patient-ready is highly desirable. Our research group has previously developed a collagen-based injectable scaffold for the treatment of a variety of wounds including wounds with deep and irregular beds. Here, we investigated the biocompatibility of our liquid scaffold in mice and compared the results to a commercially available injectable granular collagen-based product. (2) Methods: Scaffolds were applied in sub-dermal pockets on the dorsum of mice. To examine the interaction between the scaffolds and the host tissue, samples were harvested after 1 and 2 weeks and stained for collagen content using Masson's Trichrome staining. Immunofluorescence staining and quantification were performed to assess the type and number of cells infiltrating each scaffold. (3) Results: Histological evaluation after 1 and 2 weeks demonstrated early and efficient integration of our liquid scaffold with no evident adverse foreign body reaction. This rapid incorporation was accompanied by significant cellular infiltration of stromal and immune cells into the scaffold when compared to the commercial product (p < 0.01) and the control group (p < 0.05). Contrarily, the commercial scaffold induced a foreign body reaction as it was surrounded by a capsule-like, dense cellular layer during the 2-week period, resulting in delayed integration and hampered cellular infiltration. (4) Conclusion: Results obtained from this study demonstrate the potential use of our liquid scaffold as an advanced injectable wound matrix for the management of skin wounds with complex geometries.

Wound healing properties of a fibrin-based dermal replacement scaffold.

When serious cutaneous injury occurs, the innate wound healing process attempts to restore the skin's appearance and function. Wound healing outcome is affected by factors such as contraction, revascularisation, regeneration versus fibrosis and re-epithelialisation and is also strongly influenced by the pattern and extent of damage to the dermal layer. Dermal replacement scaffolds have been designed to substitute for lost tissue, provide a structure to promote dermal regeneration, and aid skin grafting, resulting in a superior healing outcome. In this study the wound healing properties of a novel fibrin-alginate dermal scaffold were assessed in the porcine wound healing model and also compared to two widely used dermal scaffolds and grafting alone. The fibrin-alginate scaffold, unlike the other scaffolds tested, is not used in combination with an overlying skin graft. Fibrin scaffold treated wounds showed increased, sustained superficial blood flow and reduced contraction during early healing while showing comparable wound closure, re-epithelialisation and final wound outcome to other treatments. The increase in early wound vascularisation coupled with a decrease in contraction and no requirement for a skin graft suggest that the fibrin-based scaffold could provide an effective, distinctive treatment option to improve healing outcomes in human patients.

SKIN SUBSTITUTES IN RECONSTRUCTION SURGERY: THE PRESENT AND FUTURE PERSPECTIVES.

The progress in critical and intensive care burn management in the 21st century has significantly reduced mortality in patients with critical burn injuries. This progress has moved the focus of burns care from simple survival to the quality of life after the burn trauma, in particular to healing of defects caused by full-thickness burns, subsequent maturation, characteristics and appearance of the scars. The benefits of the application of skin substitutes include elimination of excessive scarring, hypertrophic and keloid scar formation and subsequent contracture development. The authors of this article present the strategy of use, application and development of dermal scaffolds as well as the current trends in the use of dermal scaffolds in the treatment of full-thickness burns.

A randomized split mouth clinical study to compare the clinical outcomes of subepithelial connective graft and acellular dermal matrix in Miller's Class I recession coverage therapy.

BACKGROUND: According to the American Association of Periodontology, subepithelial connective tissue graft (SCTG) is one the most reliable surgical technique available for the treatment of gingival recession (GR) with Miller's Class I defect. However, due to its various disadvantages, alternate grafts such as acellular dermal matrix (ADM) grafts have been introduced for recession coverage. The present study compares the clinical outcome of these two grafts in treating Miller's Class I GR. MATERIALS AND METHODS: All the 15 patients participated in the study who had totally 30 bilateral Miller's Class I GR were divided randomly into SCTG group and ADM group each containing 15 defects. In the SCTG group, coronally advanced flap (CAF) with SCTG was performed, and in ADM group, CAF with ADM was done. Clinical parameters were measured on the day of surgery (baseline) and after 6 months. Data collected were statistically analyzed using paired and unpaired t-tests. RESULTS: The analysis of the data collected at the baseline and 6 months later showed that there were no statistically significant differences in the recorded clinical parameters such as probing pocket depth, clinical attachment loss, and GR depth. ADM group showed a better color match than the SCTG group, while SCTG group achieved more keratinized tissue width than ADM group. CONCLUSION: From the outcome of the current study, we can conclude that ADM is an efficient substitute for SCTG for treating Miller's Class I GR. However, additional studies with greater number of samples and lengthier follow-up periods are necessary to validate the present inference.

In vivo evaluation of an electrospun and 3D printed cellular delivery device for dermal wound healing.

Burns and chronic wounds are especially challenging wounds to heal. In efforts to heal these wounds, physicians often use autologous skin grafts to help restore mechanical and barrier functionality to the wound area. These grafts are, by nature, limited in availability. In an effort to provide an alternative, we have developed an electrospun wound dressing designed to incorporate into the wound with the option to deliver a cellular payload. Here, a blend of poly(glycolic acid) and poly(ethylene glycol) was electrospun as part of a custom fabrication method that incorporated 3D printed poly(vinyl alcohol) sacrificial elements. This preparation is unique compared to traditional electrospinning as sacrificial elements provide an internal void space for an injectable payload to be delivered to the wound site. When the construct was tested in vivo (full thickness excisional skin wounds), wound closure was slightly delayed by the presence of the scaffold in both normal and challenged wounds. Quality of healing was improved in normal wounds as measured by histomorphometrics when treated with the construct and exhibited increased neovascularization. Our results demonstrate that the extracellular matrix-like scaffold developed in this study is beneficial to healing of full thickness skin defects and may benefit challenged wounds.

Extracellular matrix deposition by adipose-derived stem cells and fibroblasts: a comparative study.

Cell-based strategies are today widely studied as possible therapies for wound healing. In this setting, fibroblasts play a key role since they are the main dermal cellular component and are responsible for extracellular matrix secretion. Several works report on the possibility of using fibroblast-derived extracellular matrix scaffolds for wound healing in skin injuries. While fibroblast-based substitutes have already been intensively studied by other groups, we focused our attention on the possibility of creating an adipose-derived stem cell (ADSC)-induced dermal scaffold for wound healing. ADSCs are a particular subset of mesenchymal stem cells present in the stromal vascular fraction of the adipose tissue. The aim of our work was to compare the ability of ADSCs and fibroblast to produce in vitro a scaffolding material, both in terms of collagen and fibronectin production. ADSCs turned out to be capable of efficiently producing a collagen and fibronectin-containing dermal matrix upon stimulation with ascorbic acid. We observed fibronectin and collagen production by ADSCs to be even more abundant when compared to fibroblasts'. Our results support the use of ADSC-induced sheets instead of fibroblast-based dermal substitutes as wound-healing strategies in full-thickness skin injuries.

Preparation and characterization of a gallium-loaded antimicrobial artificial dermal scaffold.

Artificial dermal scaffolds, which are made of natural or synthetic materials, can improve new blood vessel formation, cell migration and cell proliferation after being implanted into wounds, and they degrade slowly, playing an important role in dermal reconstruction and scar inhibition, finally achieving the goal of wound healing and functional reconstruction. Although these scaffolds have been widely used in clinical applications, biomaterial-associated infection is a deficiency or even a life-threatening problem that must be addressed, as it greatly affects the survival of the scaffolds. The gallium ion (Ga3+) is a novel metallic antimicrobial whose broad-spectrum antimicrobial properties against most bacteria encountered in burn wound infections have been confirmed, and it has been proposed as a promising candidate to prevent implant-associated infections. In this study, a gallium-loaded antimicrobial artificial dermal scaffold was successfully prepared by gallium ions and a collagen solution. The characterization results showed a porous structure with pore sizes ranging from 50 to 150 µm and a large porosity value of 97.4%. The enzymatic degradation rate in vitro was 19 and 28% after 12 and 24 h, respectively. In vitro antimicrobial testing revealed that the 1 h antibacterial rate against Staphylococcus aureus and Pseudomonas aeruginosa was close to 90%, which indicated its great antimicrobial activity. The results of the cytological evaluation showed slight effect on cell proliferation, with a relative growth rate (RGR) value of 80% and great cytocompatibility with cultured cells according to laser scanning confocal microscopy (LSCM) and scanning electron microscope (SEM). Furthermore, the successful prevention of wound infections in SD rats was confirmed with an in vivo antimicrobial evaluation, and the artificial dermal scaffolds also demonstrated great biocompatibility. This gallium-loaded antimicrobial artificial dermal scaffold exerted excellent antimicrobial activity and great biosafety, warranting further research for future clinical applications.

[Advances in the research of sensory nerve regeneration in tissue engineering skin].

Severe skin damage not only causes a mass of tissue defect, but also leads to the loss of various sensory functions. Tissue engineering skin provides a new way for high-quality wound repair, while there are still many problems in the recovery of sensory function, such as abnormality or loss of sensation of pain, touch, and temperature. Therefore, when tissue engineering skin is used to promote wound healing, regeneration and functional recovery of sensory nerve have attracted more and more attention. This article introduces the kind, distribution, regeneration, and factors influencing regeneration of sensory nerve in skin, and explores strategies in promoting regeneration of sensory nerve from dermal scaffold, seed cell, and neurturin of tissue engineering skin.

Advances in the research of sensory nerve regeneration in tissue engineering skin / 中华烧伤杂志

Severe skin damage not only causes a mass of tissue defect, but also leads to the loss of various sensory functions. Tissue engineering skin provides a new way for high-quality wound repair, while there are still many problems in the recovery of sensory function, such as abnormality or loss of sensation of pain, touch, and temperature. Therefore, when tissue engineering skin is used to promote wound healing, regeneration and functional recovery of sensory nerve have attracted more and more attention. This article introduces the kind, distribution, regeneration, and factors influencing regeneration of sensory nerve in skin, and explores strategies in promoting regeneration of sensory nerve from dermal scaffold, seed cell, and neurturin of tissue engineering skin.

Design of a Novel Two-Component Hybrid Dermal Scaffold for the Treatment of Pressure Sores.

The aim of this study is to design a novel two-component hybrid scaffold using the fibrin/alginate porous hydrogel Smart Matrix combined to a backing layer of plasma polymerized polydimethylsiloxane (Sil) membrane to make the fibrin-based dermal scaffold more robust for the treatment of the clinically challenging pressure sores. A design criteria are established, according to which the Sil membranes are punched to avoid collection of fluid underneath. Manual peel test shows that native silicone does not attach to the fibrin/alginate component while the plasma polymerized silicone membranes are firmly bound to fibrin/alginate. Structural characterization shows that the fibrin/alginate matrix is intact after the addition of the Sil membrane. By adding a Sil membrane to the original fibrin/alginate scaffold, the resulting two-component scaffolds have a significantly higher shear or storage modulus G'. In vitro cell studies show that dermal fibroblasts remain viable, proliferate, and infiltrate the two-component hybrid scaffolds during the culture period. These results show that the design of a novel two-component hybrid dermal scaffold is successful according to the proposed design criteria. To the best of the authors' knowledge, this is the first study that reports the combination of a fibrin-based scaffold with a plasma-polymerized silicone membrane.

Free Flap Donor Site Reconstruction: A Prospective Case Series Using an Optimized Polyurethane Biodegradable Temporizing Matrix.

INTRODUCTION: We recently published a 10-patient case series where free flap donor site reconstruction was performed as a 2-stage procedure using an integrating biodegradable polyurethane matrix (to form a neodermis), followed by definitive closure with an autologous split-skin graft. Two issues were revealed by this pilot study that led to further modification of the biodegradable temporizing matrix. This involved alterations to the seal thickness and bonding to the foam matrix and the introduction of fenestrations to the seal. OBJECTIVE: This article documents a second cohort of patients requiring free flap (fibular and radial forearm) donor site reconstruction with this optimized material. METHODS: The biodegradable temporizing matrix was implanted when the free flap was detached from its donor site. Subsequent integration was monitored closely. Five weeks was the usual time of integration before delamination (seal removal), dermabrasion, and definitive closure with autograft. RESULTS: Integration was complete and uncomplicated in every case, delamination occurred in 1 piece in 1 action, and subsequent graft take was 100% for every patient. Long-term scar outcomes improved compared with the pilot group. Degradation is complete by 12 months, other than occasional microscopic remnants undergoing phagocytosis. CONCLUSION: This study has reiterated that the biodegradable temporizing matrix can be implanted into humans, followed by neovascularization and integration. No infection was observed, and split-skin overgrafting was successful and uncomplicated.

Collagen/chitosan based two-compartment and bi-functional dermal scaffolds for skin regeneration.

Inspired from the sophisticated bilayer structures of natural dermis, here, we reported collagen/chitosan based two-compartment and bi-functional dermal scaffolds. Two functions refer to mediating rapid angiogenesis based on recombinant human vascular endothelial growth factor (rhVEGF) and antibacterial from gentamicin, which were encapsulated in PLGA microspheres. The gentamicin and rhVEGF encapsulated PLGA microspheres were further combined with collagen/chitosan mixtures in low (lower layer) and high (upper layer) concentrations, and molded to generate the two-compartment and bi-functional scaffolds. Based on morphology and pore structure analyses, it was found that the scaffold has a distinct double layered porous and connective structure with PLGA microspheres encapsulated. Statistical analysis indicated that the pores in the upper layer and in the lower layer have great variations in diameter, indicative of a two-compartment structure. The release profiles of gentamicin and rhVEGF exceeded 28 and 49 days, respectively. In vitro culture of mouse fibroblasts showed that the scaffold can facilitate cell adhesion and proliferation. Moreover, the scaffold can obviously inhibit proliferation of Staphylococcus aureus and Serratia marcescens, exhibiting its unique antibacterial effect. The two-compartment and bi-functional dermal scaffolds can be a promising candidate for skin regeneration.

Preparation and characterization of cross-linked carboxymethyl chitin porous membrane scaffold for biomedical applications.

Porous dermal scaffold membrane (PDSM) was successfully prepared by using a so-called sol-gel freeze-drying method. In this method, the carboxymethyl chitin (CMC) hydrosol was first cross-linked by 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), and then lyophilized to form the PDSM. For the first time, this research focused on the cross-linked CMC as the only component for three-dimensional PDSM. The effects of cross-linking conditions on the performance of the PDSM were investigated. And PDSM with optimal performance was obtained through 4-h cross-linking at 4 wt% of CMC concentration in the hydrosol, where the mass ratio of EDC to NHS to CMC was 5:3:10. The porosity of the optimized PDSM was more than 90% and the water swelling rate was above 4000%. The pore size was well distributed and was between 100 µm and 200 µm. And the tensile strength was above 0.09 MPa. The as-made PDSM could be degraded above 80% in 12 days in the presence of a 0.2mg/mL lysozyme solution. Very importantly, the PDSM had no cytotoxicity and good biocompatibility from MTT assays. Our results showed the application possibility of the as-prepared PDSM as dermal scaffold for skin tissue engineering.

A biodegradable polyurethane dermal matrix in reconstruction of free flap donor sites: a pilot study.

We have developed a biodegradable temporizing matrix (BTM) capable of supporting secondary split-skin graft-take in animal studies. We report its first long-term implantation and use as a dermal scaffold in humans. This preliminary study assesses its ability to integrate, its ease of delamination, its ability to sustain split-skin graft in complex wounds, the degree of wound contraction, and ultimately the quality of the scar at 1 year postimplantation. Ten patients were recruited, each requiring elective free flap reconstruction. Free flap donor sites created were anterolateral thigh flaps, fibular osseocutaneous flaps, or radial/ulnar forearm (RF/UF) flaps. The BTM was implanted when the flap was detached from its donor site. Dressing changes were performed twice weekly. The time elapsed between implantation and delamination depended on the type of flap and thus the wound bed left. Once integrated, the BTMs were delaminated in theatre, and the surface of the "neodermis" was refreshed by dermabrasion, prior to application of a split-skin graft. The BTM integration occurred in all patients (100% in 6 patients, with 90%, 84%, 76%, and 60% integration in the remainder). Integrated BTM sustained successful graft-take in all patients. Complete take was marred in 2 patients, over areas of BTM that had not integrated and graft application was performed too early. The BTM can be applied into wounds in humans and can integrate, persist in the presence of infection, and sustain split-skin overgrafting, despite the trial group presenting with significant comorbidities.

The Use of Fetal Bovine Dermal Scaffold (PriMatrix) in the Management of Full-Thickness Hand Burns.

OBJECTIVE: Management of full-thickness burn wounds represents a challenge when reconstructive options are not applicable. Fetal bovine dermal matrix is a bioactive collagen scaffold that assimilates into wounds and stimulates vascularization and dermal regeneration. METHODS: We present the use of fetal bovine dermal scaffold PriMatrix in the treatment of a patient who sustained scald-immersion full-thickness burns of her bilateral hands that failed conventional wound therapy. RESULTS: A 71-year-old woman with advanced Parkinson's disease sustained self-induced 5% mixed second- and third-degree scald-immersion burns of her bilateral hands and fingers. The patient underwent extensive debridement that resulted in partially avascular wounds measuring 66 cm(2) and 72 cm(2) with exposed extensor tendons and no evidence of bleeding. Meshed homograft was applied, but her hands remained partly avascular. PriMatrix fetal bovine dermal scaffold was applied to provide tissue remodeling over the bones, which allowed successful skin grafting and complete wound healing. CONCLUSIONS: Our experience shows fetal bovine dermal scaffold to be an effective method in management of complicated burn wounds in selected cases. Further studies need to be implemented to confer this conclusion.

Angiogenesis of dermal scaffold transplantation zone promoted by moboilizing endothelial progenitor cells / 中国组织工程研究

10.3969/j.issn.2095-4344.2013.24.003