Biomimetic In Vitro Model of Cell Infiltration into Skin Scaffolds for Pre-Screening and Testing of Biomaterial-Based Therapies

Abstract

Due to great clinical need, research where different biomaterials are tested as 3D scaffolds for skin tissue engineering has increased. In vitro studies use a cell suspension that is simply pipetted onto the material and cultured until the cells migrate and proliferate within the 3D scaffold, which does not mimic the in vivo reality. Our aim was to engineer a novel biomimetic in vitro model that mimics the natural cell infiltration process occurring in wound healing, thus offering a realistic approach when pre-screening and testing new skin substitutes. Our model consists of porous membrane cell culture inserts coated with gelatin and seeded with human dermal fibroblasts, inside which two different commercially available dermal substitutes were placed. Several features relevant to the wound healing process (matrix contraction, cell infiltration and proliferation, integration of the biomaterial with the surrounding tissue, and secretion of exogenous cytokines and growth factors) were evaluated. Our results showed that cells spontaneously infiltrate the materials and that our engineered model is able to induce and detect subtle differences between different biomaterials. The model allows for room for improvements or “adds-on” and miniaturization and can contribute to the development of functional and efficient skin substitutes for burns and chronic wounds.

Comparison of Decellularized Human Dermal Scaffolds versus Bovine Collagen/Elastin Matrices for in vivo Engineering of Axially Vascularized Soft Tissue Flaps in Rats

“…Furthermore, previous in vitro studies demonstrated that the absence of cross-linking in bovine collagen and elastin matrices leads to a significant decrease in stability, volume retention, and tensile strength. 19,20…”

“…Furthermore, previous in vitro studies demonstrated that the absence of crosslinking in bovine collagen and elastin matrices leads to a significant decrease in stability, volume retention, and tensile strength. 19,20 A total of 100 mg of dehydrated tissue per sample was rehydrated in 0.9% sodium chloride solution, and the mass of the tissues was then determined and reassessed after centrifugation at 1000 g. The amount of water within the scaffold and within the scaffold interspaces was thus calculated.…”

Células-tronco mesenquimais em modelo de pele humana reconstruída in vitro: aplicabilidade na engenharia tecidual

“…Adicionalmente, essas telas podem ser cultivadas com células como os queratinócitos e fibroblastos autólogos, alógenos ou neonatais (FERREIRA et al, 2011; VAN ZUIJLEN et al, 2015). O uso combinado dos fibroblastos e queratinócitos nesses substitutos dérmicos cria um modelo vivo de pele, na qual a presença e a produção de citocinas e fatores de crescimento por essas células (ZAULYANOV; KIRSNER, 2007) melhoram a regeneração dérmica e epidérmica, reduzindo a contração da ferida, acelerando a cicatrização e diminuindo a fibrose no local (COULOMB; LEBRETON; DUBERTRET, 1989;LAMME et al, 2000;PHAM et al, 2007;BALLESTEROS-CILLERO et al, 2019). Porém, a obtenção de células autólogas pode ser inviável no caso de pacientes muito debilitados, enquanto células alógenas são, geralmente, rejeitadas, não sendo utilizadas em casos de substituição permanente da pele (HULTMAN et al, 1996).…”