Compressed collagen gel as the scaffold for skin engineering

Abstract

Collagen gel scaffolds can potentially be utilized as cell seeded systems for skin tissue engineering. However, its dramatic contraction after being mixed with cells and its mechanical weakness are the drawbacks for its application to skin engineering. In this study, a compressed collagen gel scaffold was fabricated through the rapid expulsion of liquid from reconstituted gels by the application of 'plastic compression'(PC) technique. Both compressed and uncompressed gels were characterized with their gel contraction rate, morphology, the viability of seeded cells, their mechanical properties and the feasibility as a scaffold for constructing tissue-engineered skin. The results showed that the compression could significantly reduce the contraction of the collagen gel and improve its mechanical property. In addition, seeded dermal fibroblasts survived well in the compressed gel and seeded epidermal cells gradually developed into a stratified epidermal layer, and thus formed tissue engineered skin. This study reveals the potential of using compressed collagen gel as a scaffold for skin engineering.

Introduction to cell–hydrogel mechanosensing

“…These types of hydrogel are particularly useful in examining cellular behaviour owing to their biocompatibility, biodegradability and biofunctionality [68]. cornea agarose-fibrin [29] alginate-gelatin nanofibre [163] collagen [146,149,150] collagen-PLGLA nanofibre [160] alginate [34] cellulose [35] heparin [36] alginate-hyaluronic acid [33] collagen [190] collagen-chitosan [32] dextran [30,31] hyaluronic acid [44] alginate [27] collagen [23,24] dextran [25] gelatin [26] collagen [17,97] fibrin [37] agarose [51,175,179,196] alginate [126] chitosan [20,50] fibrin [42,51] gellan gum [22,51] hyaluronic acid [110] PEG [60] A key factor when examining cell-material mechano-interactions is the mechanisms of cell adhesion to the hydrogel. Cell surface receptors such as integrins bind to ligands within the hydrogel if such adhesion sites exist.…”

“…The compression technique can be manipulated to allow fluid flow out of the hydrogels in a particular direction resulting in a more aligned fibre arrangement [147,148]. Plastic compression has several applications including the development of hydrogels with incremental increases in stiffness to study the effect of stiffness on cell migration and proliferation [92,145] and it has been under examination for cornea regeneration [146,149] and dermal tissue engineering and repair [23,24]. To date, this technique has primarily been used on collagen hydrogels, because most other hydrogels are incompressible under high strains, in part, owing to their hydrophilic nature.…”

Macromolecular Crowding Effect on Cartilaginous Matrix Production: A Comparison of Two-Dimensional and Three-Dimensional Models

“…1,2 As reported by the early literatures, concept proof studies were exclusively performed with in vivo animal models due to the necessity of an in vivo environment for engineered tissue formation. [3][4][5] In recent years, with the urge of developing engineered tissue products, an in vitro tissue-engineering approach has been developed to meet this unmet need, such as in vitro engineered skin, 6,7 tendon, 8,9 and blood vessel. 10 Despite the reported success, it is obviously noted that in vitro engineered tissue could never be as mature as in vivo engineered tissue, and the maturation of engineered tissue has to be carried out in vivo, suggesting that an in vitro culture system lacks proper environmental factors that are needed for tissue maturation in vivo.…”

Collagen‐Based Biomaterials for Regenerative Medicine

“…Dense collagen hydrogels generated by plastic compression have good mechanical properties and biomimetic functions. Their structures are therefore close to the structure of connective tissues such as skin and bone [55,56].…”

“…They have bilayer structure with an epidermal part made of sheets of keratinocytes and a dermal part that is a classical collagen hydrogel (Apligraf) [45]. As classical hydrogels have some drawbacks, biomaterials such as concentrated collagen hydrogels [48,49] or hydrogels obtained by plastic compression offer promise in the improvement of materials used in chronic wound treatment [89].…”