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<p>Diabetic wounds are common in patients with type 2 diabetes; they are ischemic and inflammatory, and difficult to heal without intervention. Hyperbaric oxygen therapy (HBOT) is a standard treatment, but its effectiveness is limited to a subset of the aging population. Senescent fibroblasts, a hallmark of aging, impair wound healing, and senolytic drugs, like quercetin (<i>Q</i>), which target senescent cells, may improve healing. In this study, we developed a mathematical model that defines biological aging through two parameters, <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_2852_Article_IEq1.gif" Format="GIF" Height="12" Rendition="HTML" Resolution="72" Type="Linedraw" Width="13" /> </InlineMediaObject> <EquationSource Format="TEX">\(\eta\)</EquationSource> </InlineEquation> and <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_2852_Article_IEq2.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="20" /> </InlineMediaObject> <EquationSource Format="TEX">\(A_0\)</EquationSource> </InlineEquation>, that decline with age. These parameters reflect the biological age of an individual, where <InlineEquation ID="IEq3"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_2852_Article_IEq1.gif" Format="GIF" Height="12" Rendition="HTML" Resolution="72" Type="Linedraw" Width="13" /> </InlineMediaObject> <EquationSource Format="TEX">\(\eta\)</EquationSource> </InlineEquation> represents fibroblast proliferation and <InlineEquation ID="IEq4"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_2852_Article_IEq2.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="20" /> </InlineMediaObject> <EquationSource Format="TEX">\(A_0\)</EquationSource> </InlineEquation> represents the production of the angiogenetic protein VEGF. Our model predicts that treatment with only HBOT achieves wound closure, within normal expectable time, for patients with a limited subset pairs of <InlineEquation ID="IEq5"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_2852_Article_IEq5.gif" Format="GIF" Height="19" Rendition="HTML" Resolution="72" Type="Linedraw" Width="49" /> </InlineMediaObject> <EquationSource Format="TEX">\((\eta ,A_0)\)</EquationSource> </InlineEquation>, and this subset is increased to a larger subset by combining <i>Q</i> with HBOT. The two subsets of <InlineEquation ID="IEq6"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_2852_Article_IEq5.gif" Format="GIF" Height="19" Rendition="HTML" Resolution="72" Type="Linedraw" Width="49" /> </InlineMediaObject> <EquationSource Format="TEX">\((\eta ,A_0)\)</EquationSource> </InlineEquation> are determined explicitly by simulations of the model. To make these results applicable in clinical setting, one will have to relate the aging parameters <InlineEquation ID="IEq7"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_2852_Article_IEq1.gif" Format="GIF" Height="12" Rendition="HTML" Resolution="72" Type="Linedraw" Width="13" /> </InlineMediaObject> <EquationSource Format="TEX">\(\eta\)</EquationSource> </InlineEquation> and <InlineEquation ID="IEq8"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2025_2852_Article_IEq2.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="20" /> </InlineMediaObject> <EquationSource Format="TEX">\(A_0\)</EquationSource> </InlineEquation> to tangible marks of biological-aging factors.</p>

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Modeling treatment of diabetic wounds with oxygen therapy and senolytic drug

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  • 发表日期：

    2025年5月23日

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  • Nourridine Siewe,
  • Avner Friedman

摘要

Diabetic wounds are common in patients with type 2 diabetes; they are ischemic and inflammatory, and difficult to heal without intervention. Hyperbaric oxygen therapy (HBOT) is a standard treatment, but its effectiveness is limited to a subset of the aging population. Senescent fibroblasts, a hallmark of aging, impair wound healing, and senolytic drugs, like quercetin (Q), which target senescent cells, may improve healing. In this study, we developed a mathematical model that defines biological aging through two parameters, \(\eta\) and \(A_0\) , that decline with age. These parameters reflect the biological age of an individual, where \(\eta\) represents fibroblast proliferation and \(A_0\) represents the production of the angiogenetic protein VEGF. Our model predicts that treatment with only HBOT achieves wound closure, within normal expectable time, for patients with a limited subset pairs of \((\eta ,A_0)\) , and this subset is increased to a larger subset by combining Q with HBOT. The two subsets of \((\eta ,A_0)\) are determined explicitly by simulations of the model. To make these results applicable in clinical setting, one will have to relate the aging parameters \(\eta\) and \(A_0\) to tangible marks of biological-aging factors.