The Effect of Microporous Polysaccharide Hemospheres on Wound Healing and Scarring in Wild-Type and db/db Mice
Kyle J Miller1, Wei Cao, Mohamed M Ibrahim
1Kyle J. Miller, MD, BA, is an Orthopedic Surgery Resident, Department of Orthopedic Surgery and Rehabilitation, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Wei Cao, MD, PhD, is Attending Surgeon, Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Mohamed M. Ibrahim, MD, is Senior Research Fellow, Division of Plastic, Maxillofacial, and Oral Surgery, Duke University Medical Center, Durham, North Carolina. Howard Levinson, MD, is Associate Professor, Plastic and Reconstructive Surgery; Associate Professor, Division of Surgical Sciences; Associate Professor in Pathology, Departments of Surgery and Pathology; and Plastic and Reconstructive Surgeon, Division of Plastic, Maxillofacial, and Oral Surgery, Duke University Medical Center, Durham, North Carolina. The authors have disclosed that they have no financial relationships related to this article. Submitted May 26, 2015; accepted in revised form August 27, 2015. Acknowledgments: This work was supported in part by a grant from Medafor, Inc, now part of Bard Davol, Inc (Warwick, Rhode Island). The authors thank M. Angelica Selim, MD, of the Duke University Department of Pathology for her assistance with histology.
Background:
Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process.
Objective:
This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model.
Methods:
The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice. The effect of MPH on scarring was evaluated by applying it to the expanded polytetrafluoroethylene tube implantation model.
Results:
In wild-type mice, topically applied MPH increased epithelial thickness. Levels of α-smooth muscle actin (α-SMA) were decreased in MPH-treated wild-type wounds, whereas Rho-associated protein kinase 2 (ROCK2) and transforming growth factor β levels were increased. In db/db mice, topical wound MPH application decreased epithelial thickness and delayed wound closure. The db/db wounds displayed an increased collagen index. The ROCK2 was increased in a similar manner to wild-type mice, whereas α-SMA and transforming growth factor β levels were decreased. The MPH-treated expanded polytetrafluoroethylene tube mice showed increased α-SMA levels and depressed ROCK2 levels. There were no changes in histologic parameters of the foreign body response.
Conclusions:
The results suggest that MPH does not adversely impact wound healing in wild-type mice, both topically and around implants, but prolongs time to closure and diminishes thickness in db/db wounds. The MPH application alters contractile proteins in all wound models. These changes could have downstream effects on the wound healing process, and further investigation into the use of MPH in altered or impaired states of wound healing is warranted.
Insights
Microporous polysaccharide hemosphere powder (MPH) aids wound healing in normal mice but delays closure and reduces thickness in diabetic mice. MPH alters contractile proteins, warranting further study in impaired wound healing.
Area of Science:
- Biomedical Engineering
- Wound Healing Research
- Tissue Repair Mechanisms
Background:
- Hemostasis is the critical first step in wound healing.
- Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent with potential effects on tissue repair.
- Understanding MPH's impact on wound healing is crucial for its clinical application.
Purpose of the Study:
- To investigate the effects of MPH on wound healing in wild-type and diabetic murine models.
- To assess MPH's influence on scarring using a foreign body response model.
- To elucidate the molecular mechanisms underlying MPH's effects on wound healing.
Main Methods:
- Excisional wounds were created and treated with MPH in wild-type C57BL/6 and diabetic db/db mice.
- Scarring was evaluated using an expanded polytetrafluoroethylene (ePTFE) tube implantation model with MPH application.
- Histological and molecular analyses, including α-smooth muscle actin (α-SMA), ROCK2, and TGF-β, were performed.
Main Results:
- In wild-type mice, MPH increased epithelial thickness and altered levels of α-SMA, ROCK2, and TGF-β.
- In db/db mice, MPH decreased epithelial thickness, delayed wound closure, and increased collagen index, while altering protein levels differently than in wild-type mice.
- MPH application around ePTFE implants in mice increased α-SMA and decreased ROCK2, with no observed changes in foreign body response histology.
Conclusions:
- MPH does not negatively affect wound healing in wild-type mice but impairs healing in diabetic mice.
- MPH application consistently modifies contractile protein expression across different wound models.
- Further research is needed to explore MPH's utility in managing complex or compromised wound healing scenarios.
