A potential dermal substitute using decellularized dermis extracellular matrix derived bio-ink

Abstract

Upon bioprinting, cells are mixed with a biomaterial to fabricate a living tissue, thus emphasizing the importance of biomaterials. The biomaterial used in this study was a bio-ink prepared using skin decellularized extracellular matrix (dECM). Skin dECM was extracted by treating the dermis with chemicals and enzymes; the basic structural and functional proteins of the ECM, including collagen, glycosaminoglycans (GAGs), bioreactive materials and growth factors, were preserved, whereas the resident cells that might cause immune rejection or inflammatory responses were removed. The bio-ink based on dECM powder, together with human dermal fibroblasts (HDFs), was loaded into the nozzle of the 3D bioprinter to create the 3D construct. This construct underwent gelation with changing temperature while its shape was maintained for 7 days. The cells showed over 90% viability and proliferation. By analysing the gene expression pattern in the cells of the construct, the skin regenerative mechanism of the bio-ink was verified. Microarray results confirmed that the gene expression related to skin morphology and development had been enhanced because the bioreactive molecules and growth factors, in addition to residual ECM in dECM, provided an optimal condition for the HDFs.

Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration

“…Won and colleagues conducted another innovative study on decellularized ECM derived from a pig dermis; the authors obtained a printable bio-ink that was mixed with human dermal fibroblasts (HDFs) to produce a construct loaded with human cells. The residual ECM containing collagen and GAG, as well as bioactive molecules and growth factors, provided cells with an environment identical to that in the tissue, helping with the viability and proliferation of HDF in the construct [ 122 ].…”

New Nanotechnologies for the Treatment and Repair of Skin Burns Infections

“…A bio-ink prepared using skin decellularized ECM has been recently described [104]. The bio-ink was obtained by combining decellularized ECM (containing collagen, glycosaminoglycans and growth factors and free from immune-reactive cells) with human dermal fibroblasts.…”

A Concise Review on Tissue Engineered Artificial Skin Grafts for Chronic Wound Treatment: Can We Reconstruct Functional Skin Tissue In Vitro?

“…Importantly, it was observed that co-culture systems have advantages over monocultures since fibroblasts have the ability to promote keratinocyte growth and differentiation by either GF release or direct cell-cell contact, whereas GFs secreted by keratinocytes stimulate fibroblast proliferation ( Figure 6) [2,49,50]. of skin cells purchased from the cell culture bank [71,72]. The main disadvantage of the use of isolated primary cells is their low proliferation potential, making it difficult to obtain a sufficient number of cells for cellular skin graft production [49].…”

“…Nevertheless, it is known that cell lines may reveal a completely different gene expression compared to primary cells [65,66], and thus primary cultures should be preferentially used for both skin graft production and biocompatibility testing of new biomaterial-based skin substitutes. Indeed, most cellular artificial skins were developed using either isolated primary fibroblasts and/or keratinocytes [67][68][69][70] or primary culture of skin cells purchased from the cell culture bank [71,72]. The main disadvantage of the use of isolated primary cells is their low proliferation potential, making it difficult to obtain a sufficient number of cells for cellular skin graft production [49].…”

“…Mahmoud et al [ 87 ] fabricated norfloxacin-loaded collagen/chitosan sponges, which enhanced the regeneration of full-thickness skin wounds in a rat model without any side-effects. Won et al [ 72 ] developed an innovative cellular dermal skin graft that was prepared using freeze-dried and powdered skin decellularized extracellular matrix (dECM), which had all functional proteins of the ECM preserved, including collagen, GAGs, and GFs. Powdered skin dECM was used for the preparation of bionk that was subsequently 3D bioprinted with human dermal fibroblasts to obtain functional cellular dermal construct.…”