Immunohistochemical Characterization of the Inflammatory Responses in Wound Healing and the Use of the Subcutaneous Polyvinyl Alcohol (PVA) Sponge Implantation for Evaluation of the Healing Process

Abstract

Background: Biologic and synthetic biomaterials have been used for various medical applications and research studies. Subcutaneous implantation of Polyvinyl Alcohol (PVA) sponge is a commonly used experimental model to study the underlying mechanisms of wound healing. As a research tool, PVA sponge is useful for analyzing the granulation tissue formation and tissue regeneration. Hypothesis and Aims: PVA sponge model might show a different inflammatory response from the open incisional wound model because it reflects the host response to a foreign body. Thus, this study aims to characterize the inflammatory responses in the two models. Materials and Methods: Adult male albino rats were used to produce the two models of wound healing. Through a midline incision, two PVA sponges were implanted subcutaneously on each side. Two incisional dermal wounds were produced on the dorsum of each rat. At the end of the experiments, the sponges and the incisional wounds were harvested at different time points for assessing the inflammatory responses. Immunohistochemical staining was used to study the cellular localization and the profile of the inflammatory markers iNOS and TGF Beta-and Western blot analysis used to study their protein levels. Results: Immunohistochemical staining and Western blot analysis showed a distinct variability in the inflammatory responses between the two wound models. PVA sponge implantation model showed a delayed and a persistent inflammation started 3 days post-implantation and persisted as long as the sponge existed. On the other hand, the incisional wound model showed an early and a time limited response started 1 day and ended 5-7 days post-wounding. Moreover, the inflammatory mediators iNOS and TGF Beta-1 were differentially regulated in both models. While, they showed a similar profile along the time course in the PVA sponge model. They showed a differential profile in the open wound model. Conclusion: subcutaneous PVA sponge provides an ideal reproducible model for use in inflammation research. However, it may not be a reliable model for wound healing modulation studies. It elects inflammatory response considerably different from what happens in the tissues. Furthermore, in open wound model, inflammation is differentially controlled by iNOS and TGF Beta-1. Therefore, abnormal wound healing conditions could be treated by pharmacological intervention using nitric oxide (NO) and TGF Beta-1 modulators.