Thermal injury healing in the context of neocollagenogenesis induction: preclinical randomized experimental study

Background. The healing of skin wounds having various etiologies is known to involve a multistep process characterized by certain intercellular interactions affecting dermal cells, their attachment, migration, and differentiation. Here, recovery is interpreted as the return of dermis to its original state. The fact is, however, that the dermal extracellular matrix (ECM) is structurally impaired, which suppresses the regulatory and repository functions of the dermis, leading to the formation of a scar that inhibits several biological functions in the affected area and causes aesthetic problems associated with mobility.

Objectives. To evaluate the structural features of dermis during wound healing using a calcium-containing biodegradable implant.

Methods. The study used 60 rats that were inflicted with a third-degree burn injury (partially damaged dermis). The selected animals were divided into two groups: experimental and control. On post-burn day 14, a calcium-containing biodegradable implant was administered to rats from the experimental group, while a sterile saline solution was used in the control group. Material was sampled at two months (74 days) and four months (134 days). In order to assess the morphological state of the burn area, its sections were stained with hematoxylin and eosin, according to Mallory and Van-Gieson. For the selective detection of collagens, immunohistochemical tests using antibodies to collagen types I and III (Abcam, England) were employed. To characterize dermal cells, the authors used antibodies to vimentin (LabVision, USA), as well as to СD-68 (cluster of differentiation 68), α-SMA (alpha-smooth muscle actin), CD-105 (cluster of differentiation 105), and VEGF (vascular endothelial growth factor) receptors (Abcam, England). The obtained results were processed using the Statistica 6 software (StatSoft, USA).

Results. The administration of a calcium-containing biodegradable filler during the burn healing process was found to ensure local fibroblast activation with the formation of collagen types I and III. When the implant residence time was prolonged up to four months, an increase in the number of macrophages expressing CD-68 receptors was observed. Of note is that these cells retained their localization, while α-SMA-expressing cells were localized in both the superficial and deep dermal compartments. The number of cells expressing CD-105 and VEGF rose as well.

Conclusion. The use of the biodegradable filler is found to be promising in terms of post-burn dermal regeneration, as well as providing a dermal ECM, whose collagen network composition and assembly are similar to the original. Here, macrophages act as the primary synthesis regulators of the dermal ECM and stimulate fibroblasts, which ensures re-epithelialization and angiogenesis of the inflicted area.