Hyaluronic acid biomaterial for human tissue‐engineered skin substitutes: Preclinical comparative in vivo study of wound healing

Abstract

Background There is not an ideal biomaterial for tissue-engineered skin substitutes (TESSs), and most of the studies or existing therapies use xenogeneic origin natural biomaterials or biosynthetic scaffolds. Objective To analyse clinical, histological integration and homeostasis parameters of a human TESS manufactured with fibrin-hyaluronic acid biomaterial (HA-Skin), grafted in immunodeficient mice for 8 weeks, and compared with the gold standard treatment (Autograft), a human TESS manufactured with fibrin-agarose biomaterial (AG-Skin) and secondary wound healing dressings. Methods Human TESSs and autografts were implanted into BALB/c mice after surgical excision. Secondary wound healing approach was achieved with biosynthetic collagen wound dressing (Biobrane â) and fibrin-hyaluronic acid or fibrin-agarose biomaterial without cells (Total N = 44). Clinical integration and homeostasis parameters were evaluated every two weeks for two months. Histological and immunohistochemical analyses were performed four and eight weeks after grafting. Results HA-Skin, AG-Skin and Autograft groups showed a proper clinical integration and epithelization eight weeks later. Scar evaluation revealed better results for Autograft and HA-Skin. Homeostasis analysis indicated similar values of transepidermal water loss and elasticity between HA-Skin (6.42 AE 0.75 g/h/m 2 , 0.42 AE 0.08 AU), Autograft (6.91 AE 1.28 g/h/m 2 , 0.40 AE 0.08 AU) and healthy mouse skin (6.40 AE 0.43 g/h/m 2 , 0.35 AE 0.03 AU). Histological results showed that human TESSs and autografts presented better skin structuration and higher expression of cytokeratins. Conclusions This study suggests that human TESS based on fibrin-hyaluronic acid biomaterial could be suitable for clinical application in the treatment of several dermatological pathologies (wound healing).

Cytotoxicity and Epidermal Barrier Function Evaluation of Common Antiseptics for Clinical Use in an Artificial Autologous Skin Model

“…Furthermore, it stimulates early inflammation, which is critical for initiating wound healing, but also reduces long-term inflammation. When compared to autografts, BASS based on fibrin-HA showed similar homeostasis parameters and restored epidermal barrier function in a wound mouse model, promoting the formation of a histological architecture very similar to normal skin [13].…”

“…The dermis was incubated for 18-24 h in a 2 mg/mL solution of type I collagenase (Gibco, Thermo Fisher Scientific, California, USA) and neutralized with specific medium for dermal fibroblasts culture (DFM). The epidermis incubated with TrypLE Select 10× (Gibco, Thermo Fisher Scientific, California, USA) for 10 cycles of 15 min per cycle and neutralized with specific medium for the keratinocyte culture (KTM) [13]. Cell suspensions were centrifuged at 300× g for 10 min.…”

“…Before taking the measurement, dehydration by controlled pressure of the BASS using a glass disc of 85 g as shot for 2 min was necessary to improve their biomechanical properties [13]. The dehydrated BASS was placed in the Franz cell and 0.5 g of mupirocin 20 mg/g (excipients; macrogol 400 and polyethylenglycol 3350, ISDIN, Barcelona, Spain) was applied.…”

Advanced Medical Therapies in the Management of Non-Scarring Alopecia: Areata and Androgenic Alopecia

“…This strategy may contribute to the treatment of deep skin injuries and to the understanding of skin regeneration. Many dermal-epidermal composites or skin equivalents have been described to use in the clinic but the inability of these skin constructs to regenerate epidermal appendages, such as hair follicles, sebaceous, and sweat glands remains a major challenge [73][74][75].…”

Eignung biologischer azellulärer dermaler Matrices als Hautersatz

“…Zell-und Basalmembranreste auf DED waren offensichtlich ausreichende Ankerpunkte, um die notwendige epitheliale Adhäsion auf dieser Matrix für den Nachweis nach histologischer Aufarbeitung zu gewährleisten. Eine Möglichkeit, die Reepithelialisierung und keratinozytäre Verankerung zu fördern [25,26], wäre z. B. der exogene Zusatz von Hyaluronsäure, die jedoch keinen Einfluss auf die lokale Entzündungsreaktion hat [25].…”