Three Dimensional Printing Bilayer Membrane Scaffold Promotes Wound Healing

Abstract

Full-thickness skin wounds are common and could be a heavy physical and economic burden. With the development of three dimensional (3D) printing technology, skin-like constructs have been fabricated for skin wound healing and regeneration. Although the 3D printed skin has great potential and enormous advantages before vascular networks can be well-constructed, living cells are not recommended for 3D skin printing for in vivo applications. Herein, we designed and printed a bilayer membrane (BLM) scaffold consisting of an outer poly (lactic-co-glycolic acid) (PLGA) membrane and a lower alginate hydrogel layer, which respectively mimicked the skin epidermis and dermis. The multi-porous alginate hydrogel of the BLM scaffolds promoted cell adhesion and proliferation in vitro, while the PLGA membrane prevented bacterial invasion and maintained the moisture content of the hydrogel. Skin regeneration using the bilayer scaffold was compared with that of PLGA, alginate hydrogel and the untreated defect in vivo. Tissue samples were analyzed using histopathological and immunohistochemical staining of CD31. In addition, mRNA expression levels of collagen markers [collagen type 1 alpha 1 (COL1a1) and collagen type 3 alpha 1 (COL3a1)] and inflammatory markers [interleukin-1β (IL-1β), as well as tumor necrosis factor (TNF-α)] were measured. Conclusively, the application of BLM scaffold resulted in highest levels of best skin regeneration by increasing neovascularization and boosting collagen I/III deposition. Taken together, the 3D-printed BLM scaffolds can promote wound healing, and are highly suitable for a wide range of applications as wound dressings or skin substitutes.

Recent advances on polymeric hydrogels as wound dressings

“…Ilhan et al 119 printed a SA/PEG hydrogel and loaded Satureja cuneifolia plant extract (SC), which had a good effect on the treatment of diabetic wound as well as good antibacterial ability. Wang et al 120 designed a bilayer membrane (BLM) scaffold composed of poly (lactic-co-glycolic acid) (PLGA) and alginate. The alginate layer was fabricated on the surface of the PLGA membrane by 3D printing, which mimicked the dermis and could promote cell adhesion and proliferation in vitro .…”

Next-generation surgical meshes for drug delivery and tissue engineering applications: materials, design and emerging manufacturing technologies

“…The obtained implant provided a moist and insulated environment for the wound. Additionally, it successfully acted as barrier against S. aureus; it showed good biocompatibility (with murine L929 cells), and it accelerated wound healing in vivo (rat model, complete healing in 12 days), promoting an initial and constructive inflammation and stimulating vascularization and collagen deposition [166]. Another device was developed by Afghah et al whose included silver nitrate particles in the formulation to provide antibacterial effects to the dressing.…”

Recent Trends in Three-Dimensional Bioinks Based on Alginate for Biomedical Applications

“…As a result, the regeneration of squamous epithelium of uniform thickness and formation of dense collagen fibers facilitated, and thus, improved the strength and tension resistance of scar tissue [ 140 ]. In a similar study, Wang et al [ 141 ] designed and printed a bilayer membrane (BLM) scaffold consisting of an outer poly (lactic-co-glycolic acid) (PLGA) membrane and a lower Alg hydrogel layer, which mimicked the skin epidermis and dermis, respectively. The first layer of PLGA nanofiber membrane was prepared using high voltage printing.…”

“…The first layer of PLGA nanofiber membrane was prepared using high voltage printing. In contrast, the second layer was fabricated by printing Alg hydrogel on the surface of the PLGA nanofiber membrane [ 141 ]. They observed porous Alg hydrogel promoted cell adhesion and proliferation, compared with PLGA.…”

“…After implantation in the dorsal wound of rats, the PLGA and Alg hydrogel scaffold presented the ability to promote inflammation, neovascularization, and collagen I/III deposition and improved wound healing. They believed that the 3D-printed scaffold is an extraordinarily promising type of wound dressing and skin substitute [ 141 ]. Overall, Alg-based dressings is a proper choice in wound dressings, as it has been considered by high water uptake, increased porosity, and non-immunogenic effects.…”