Advanced Biofabrication Strategies for Skin Regeneration and Repair

Abstract

Skin is the largest organ of human body, acting as a barrier with protective, immunologic and sensorial functions. Its permanent exposure to the external environment can result in different kinds of damage with loss of variable volumes of extracellular matrix. For the treatment of skin lesions, several strategies are currently available, such as the application of autografts, allografts, wound dressings and tissue-engineered substitutes. Although proven clinically effective, these strategies are still characterized by key limitations such as patient morbidity, inadequate vascularization, low adherence to the wound bed, the inability to reproduce skin appendages and high manufacturing costs. Advanced strategies based on both bottom-up and top-down approaches offer an effective, permanent and viable alternative to solve the abovementioned drawbacks by combining biomaterials, cells, growth factors and advanced biomanufacturing techniques. This review details recent advances in skin regeneration and repair strategies, and describes their major advantages and limitations. Future prospects for skin regeneration are also outlined.

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

“…Although the epidermis is an avascular layer, it is under constant renewal due to the presence of epidermal basal cells and stem cells in the basal layer and hair follicles [79]. The main cellular constituents include keratinocytes, melanocytes, Merkel cells and Langerhans cells [13,149]. The underlying dermis, separated from the epidermis by a basement membrane, is mainly composed of ECM molecules arranged in a dense matrix of connective tissue rich in collagen and elastin fibres that provides structural and mechanical support to the skin [15].…”

“…The clinical 'gold standard' therapy remains the application of split thickness autologous skin grafts [52,149,176]. Liquid and semi-solid preparations, such as creams (e.g.…”

“…Bioengineered skin substitutes represent the most advanced products available for skin wounds, allowing the regeneration of both epidermal and dermal skin layers [23,50,138,176]. Major limitations are the permanent closure of the wound, inadequate vascularization, high manufacturing costs and lack of skin appendages [50,149].…”

“…The integumentary system comprises the skin and respective appendages (hair, nails and sweat glands) and is responsible for many vital functions in the body, such as the homeostasis, protection, and transmission of sensorial information [52,149,201]. Skin is the most superficial and the largest organ of the human body, acting as an efficient barrier at the interface between the internal organs and the external environment.…”

“…However, in certain types of skin wounds, such as deep burns and chronic wounds, more sophisticated and effective treatments are usually needed [20,50,87,212]. Advanced therapies assume a prominent role in the management of such wounds, as they explore the basic principles and elements of tissue engineering to produce both cellular and acellular constructs for skin regeneration [52,109,149]. In the most classical approach, known as scaffold-based or top-down, scaffolds are fabricated through either conventional or additive manufacturing processes, and subsequently seeded with autologous or allogeneic cells.…”