Effect of pore size and cross-linking of a novel collagen-elastin dermal substitute on wound healing

Abstract

Collagen-elastin (CE) scaffolds are frequently used for dermal replacement in the treatment of full-thickness skin defects such as burn wounds. But little is known about the optimal pore size and level of cross-linking. Different formulations of dermal substitutes with unidirectional pores were tested in porcine full-thickness wounds in combination with autologous split skin mesh grafts (SSG). Effect on wound healing was evaluated both macro- and microscopically. CE scaffolds with a pore size of 80 or 100 μm resulted in good wound healing after one-stage grafting. Application of scaffolds with a larger average pore size (120 μm) resulted in more myofibroblasts and more foreign body giant cells (FBGC). Moderate crosslinking impaired wound healing as it resulted in more wound contraction, more FBGC and increased epidermal thickness compared to no cross-linking. In addition, take rate and redness were negatively affected compared to SSG only. Vascularization and the number of myofibroblasts were not affected by cross-linking. Surprisingly, stability of cross-linked scaffolds was not increased in the wound environment, in contrast to in vitro results. Cross-linking reduced the proliferation of fibroblasts in vitro, which might explain the reduced clinical outcome. The non-cross-linked CE substitute with unidirectional pores allowed one-stage grafting of SSG, resulting in good wound healing. In addition, only a very mild foreign body reaction was observed. Cross-linking of CE scaffolds negatively affected wound healing on several important parameters. The optimal non-cross-linked CE substitute is a promising candidate for future clinical evaluation.

To Cross-Link or Not to Cross-Link? Cross-Linking Associated Foreign Body Response of Collagen-Based Devices

“…The same host response tendency to EDC cross-linked tissue grafts was observed for EDC crosslinked collagen-elastin sponges (non-commercial materials) 177 ; the low degree of EDC cross-linking (0.3 mM EDC) increased stability of the scaffolds and supported tissue regeneration, although it delayed the wound healing phases. In contrast, the medium degree of EDC cross-linking (0.5 mM EDC) impaired wound healing, induced more macrophages and FBGCs, and scarring was evidenced 177 .…”

“…In contrast, the medium degree of EDC cross-linking (0.5 mM EDC) impaired wound healing, induced more macrophages and FBGCs, and scarring was evidenced 177 . Furthermore, low dose EDC cross-linked collagen conduits and sponges (noncommercial materials) have been shown to increase guidance of regenerating axons through distal peripheral nerve sections without obvious macroscopic signs of inflammation or neuroma formation [178][179][180] .…”

Effectiveness of wound healing using the novel collagen dermal substitute INSUREGRAF®

“…1c and d. The pore structure formed in the vertical direction, and was generally parallel within the collagen sponge using the freeze-drying method. 21,22 The pore distribution and porosity of INSUREGRAF® were similar to those of Matriderm®, which can be mainly adjusted from 20 to 90 mm (Fig. 2b).…”

About ATMPs, SOPs and GMP: The Hurdles to Produce Novel Skin Grafts for Clinical Use

“…It contains all of the epidermis, but only remnants of the dermis. This lack of dermal tissue frequently leads to significant scarring and wound contraction due to the lack of dermal regeneration within the wound area, resulting in non-ideal outcomes regarding functionality and cosmetics [1,2,3,4]. Therefore, split-thickness skin is often used in combination with a dermal template, such as Integra artificial skin [1,3,5,6,7,8,9], Matriderm® (MedSkin Solutions Dr. Suwelack, Billerbeck, Deutschland) [4,10,11], or other collagen-elastin scaffolds [2].…”