Comparison of the polyvinyl alcohol sponge and expanded polytetrafluoroethylene subcutaneous implants as models to evaluate wound healing potential in human beings

Abstract

Our current understanding of the complex processes involved in wound healing is based mainly on studies of animal models. Although this information has been useful, it may not totally reflect the response found in human beings. For example, human beings have a tendency to either "overheal," as seen in keloids and hypertrophic scar formation, or have deficient healing, as seen in chronic ulcer formation. No animal models are available to analyze these human clinical pathologic conditions. Therefore the objective of this study was to analyze the wound healing response in a large population (n = 40) of normal healthy human beings as a first step to begin studies of abnormal human wound healing. Simultaneously, a comparison was made between the polyvinyl alcohol implant and the expanded polytetrafluoroethylene implant model. Under sterile conditions with the use of local anesthesia, two preweighed polyvinyl alcohol implants and two standard 6 cm expanded polytetrafluoroethylene implants were placed subcutaneously in the upper arm of each subject. High-performance liquid chromatography was used to quantitate isoleucine and hydroxy-l-proline in acid hydrolysates of each implant. Isoleucine was used as an indicator of protein content in the tissue sample, whereas hydroxyproline reflected collagen content. No infectious or hemorrhagic complications were found in the 40 volunteers included in the study. No significant difference was found in isoleucine or hydroxy-l-proline content between postoperative day 7 polyvinyl alcohol implants and day 14 polyvinyl alcohol implants. In contrast, both isoleucine and hydroxy-l-proline content were significantly increased in day 14 expanded polytetrafluoroethylene implants compared with day 7 implants (p < 0.005 and p < 0.001, respectively). In addition, the ratio of hydroxy-l-proline to isoleucine was significantly increased in day 14 expanded polytetrafluoroethylene implants compared with day 7 expanded polytetrafluoroethylene and both day 7 and day 14 polyvinyl alcohol implants (p < 0.001). This observation suggests that by 14 days implantation of expanded polytetrafluoroethylene stimulated an increased deposition of collagen. No significant differences were found in the hydroxy-l-proline to isoleucine ratios among day 7 expanded polytetrafluoroethylene, day 7 polyvinyl alcohol, and day 14 polyvinyl alcohol implants. Histologic analyses correlated with the biochemical findings. These results suggest that expanded polytetrafluoroethylene may be the preferred implant for studies designed to examine pathologic processes associated with retarded wound healing. In contrast, the polyvinyl alcohol implant may be better suited for studies where a low background response is required. Moreover, the extreme variability in normal healthy volunteers seen in this study correlates clinically with the finding that, among the normal adult human population, there is a heterogeneous wound healing response.

The Polyvinyl Alcohol Sponge Model Implantation

“…For studies in humans and some other species, sponges may need to be placed in a porous silicone tubing to prevent the sponge from being encapsulated and to allow ease of removal 4,8 . The location of the sponge implantation can be altered based on desired results and skill of technician.…”

“…The steel wire mesh cylinder model has a lag phase of infiltration after implantation and requires a long amount of time before granulation tissue formation begins 1 . Later stages of wound healing are best analyzed using the ePTFE model 1,4 . The Cellstick is a cellulose sponge inside a silicon tube model which is typically used for studying human surgery wounds and wound fluid 2 .…”

An Entropy-Based Automated Cell Nuclei Segmentation and Quantification: Application in Analysis of Wound Healing Process

“…It is of interest to note that many of the characteristics and cell functions that are manifest in cancer are also found during wound healing [3]. New research strategies to explore human wound healing are now available and allow for the in-depth investigation of the specific cell types that participate in the highly orchestrated events that occur during tissue injury and repair [4, 17]. Development of such translational computation medical systems has been and will be providing invaluable insight into understanding the complex nature of the wound healing process [18, 19].…”

Mice engrafted with human hematopoietic stem cells support a human myeloid cell inflammatory response in vivo

“…We show that human leukocytes are actively mobilized to the implanted PVA sponges and identified the populations of infiltrating human leukocytes. In the past, the study of human myeloid cell differentiation at sites of human inflammation has been limited because of the focus on either blood and bone marrow‐derived macrophages for in vitro analysis or subcutaneous synthetic implants from human volunteers in vivo . In contrast, mechanisms of mouse inflammation have advanced rapidly because of the availability of gene knockout and transgenic tools for the study of myeloid cell responses (i.e., macrophage and dendritic cell biology).…”

“…Building on an emerging interest in uniquely human genes and their possible role(s) in the human response to injury, we explored the feasibility of adapting subcutaneous implants of polyvinylalcohol (PVA) sponges as an experimental model of human inflammation . This model is based on human studies of the inflammatory response to foreign objects and to characterize the subtypes of cells that infiltrate human wounds . Here, we compare the inflammation response of mice reconstituted with human CD34 + ‐hematopoietic stem and progenitor cells (CD34 + ‐HSPCs) with control mice lacking CD34 + ‐HSPCs using a combination of flow cytometry and immunohistochemistry to define the kinetics and profile of cells recruited to the PVA sponge implant.…”