Differential Capability of Clinically Employed Dermal Regeneration Scaffolds to Support Vascularization for Tissue Bioengineering

The loss of skin integrity has always represented a major challenge for clinicians dealing with dermal defects, such as ulcers (diabetic, vascular and chronic), postoncologic resections (i.e., radical vulvectomy) or dermatologic disorders. The introduction in recent decades of acellular dermal matrices (ADMs) supporting the repair and restoration of skin functionality represented a significant step toward achieving clean wound repair before performing skin grafts. Hard-to-heal ulcers generally depend on local ischemia and nonadequate vascularization. In this context, one possible innovative approach could be the prevascularization of matrices with vessel-forming cells (inosculation). This paper presents a comparative analysis of the most widely used dermal templates, i.e., Integra® Bilayer Matrix Wound Dressing, PELNAC®, PriMatrix® Dermal Repair Scaffold, Endoform® Natural Dermal Template, and Myriad Matrix®, testing their ability to be colonized by human adult dermal microvascular endothelial cells (ADMECs) and to induce and support angiogenesis in vitro and in vivo. By in vitro studies, we demonstrated that Integra® and PELNAC® possess superior pro-adhesive and pro-angiogenetic properties. Animal models allowed us to demonstrate the ability of preseeded ADMECs on Integra® to promote the engraftment, integration and vascularization of ADMs at the site of application.

A Comparative Study of Engineered Dermal Templates for Skin Wound Repair in a Mouse Model

Engineered dermal templates have revolutionised the repair and reconstruction of skin defects. Their interaction with the wound microenvironment and linked molecular mediators of wound repair is still not clear. This study investigated the wound bed and acellular “off the shelf” dermal template interaction in a mouse model. Full-thickness wounds in nude mice were grafted with allogenic skin, and either collagen-based or fully synthetic dermal templates. Changes in the wound bed showed significantly higher vascularisation and fibroblast infiltration in synthetic grafts when compared to collagen-based grafts (P ≤ 0.05). Greater tissue growth was associated with higher prostaglandin-endoperoxide synthase 2 (Ptgs2) RNA and cyclooxygenase-2 (COX-2) protein levels in fully synthetic grafts. Collagen-based grafts had higher levels of collagen III and matrix metallopeptidase 2. To compare the capacity to form a double layer skin substitute, both templates were seeded with human fibroblasts and keratinocytes (so-called human skin equivalent or HSE). Mice were grafted with HSEs to test permanent wound closure with no further treatment required. We found the synthetic dermal template to have a significantly greater capacity to support human epidermal cells. In conclusion, the synthetic template showed advantages over the collagen-based template in a short-term mouse model of wound repair.

A Retrospective Study on the Use of Dermis Micrografts in Platelet-Rich Fibrin for the Resurfacing of Massive and Chronic Full-Thickness Burns

The coverage of massive burns still represents a big challenge, even if several strategies are to date available to deal with this situation. In this study, we describe the use of a combination of platelet-rich fibrin and micrograft spray-on skin in order to increase the yield of grafted cells in patients. We treated a total of five patients, of which two were affected by massive burns and three with chronic burn wounds. Briefly, autologous micrografts were obtained by Rigenera technology using a class I medical device called Rigeneracons. The micrografts were then combined with PRF and sprayed on the wound bed by a Spraypen. Before applying PRF/micrograft spray-on skin, the wound bed was covered with an Integra® dermal template, and the wounds were dressed with a layer of antimicrobial dressing applied directly over the silicone layer. When the silicone layer of the dermal template started showing signs of separation, the wound was considered ready for grafting. In all cases, we observed a fast and complete skin graft on average after 7-10 days by PRF/micrograft spray-on skin treatment. In particular, two patients with massive burns reported rapid reepithelialization, and three patients with chronic burn wounds, two of whom had failed skin grafts before the procedure, had complete wound healing within a week. In conclusion, the results showed in this study suggest that the use of PRF/micrograft spray-on skin represents a promising approach in the management of burns or chronic burn wounds.

Skin Epidermis and Adnexa Regrowth Induced by Treatment With Artificial Dermal Template After Full-Thickness Skin Wound

Full-thickness skin wounds are common accidents. Although healing can be achieved by treatments like autologous skin grafts, donor site morbidity is hardly evitable. In this article, we provide compelling evidence demonstrating that artificial dermal template (ADT)-treated wound healing is achieved by regrowth of skin epidermis as well as adnexa without skin grafts by use of rodent models. First, by fixating a chamber to the wound edge, we confirmed that wound healing was achieved by regeneration instead of contracture. We found highly proliferative cells in adnexa in the newly formed skin. In the distal edge of newly formed skin, we identified immature hair follicles at early developing stages, suggesting they were newly regenerated. Second, we observed that the Lgr5-positive hair follicle stem cells contributed to formation of new hair follicles through a lineage tracing model. Also, Lgr6-positive cells were enriched in distal edge of newly developed skin. Finally, WNT signaling pathway mediators were highly expressed in the new skin epidermis and adnexa, implying a potential role of WNT signaling during ADT treatment-stimulated skin regrowth. Taken together, our findings demonstrated that full skin regrowth can be induced by ADT treatment alone, thus arguing for its wide clinical application in skin wound treatment.

Chronic Scalp Ulcer 35 Years after Skull Trepanation Surgery and Radiotherapy for Oligodendroglioma: A Further Example of Immunocompromised Cutaneous Districts

BACKGROUND: Chronic ulcers of the scalp have a variety of underlying pathologies. In case of cancer patients, a second malignancy must be excluded.CASE REPORT: A 78-year-old female patient presented to our department with a large soft tissue defect on the frontotemporal left side. The lesion was about 3 cm in diameter with exposed bone and inflammatory soft tissue on the edges of the defect. About 35 years ago, she had undergone a combined neurosurgery with skull trepanation and radiotherapy for an oligodendroglioma. Three years ago, sandwich transplantation with the dermal template and meshed skin graft failed. Now she re-presented with inflammatory ulcer borders. A complex defect repair was performed after exclusion of a second malignancy.CONCLUSION: Chronic scalp ulcers may be the result immunocompromised cutaneous districts and need a complex reconstruction.