Modeling stem/progenitor cell-induced neovascularization and oxygenation around solid implants.

Modeling stem/progenitor cell-induced neovascularization and oxygenation around solid implants.
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模拟固体植入物周围干/祖细胞诱导的新血管形成和氧合。

DOI:
10.1089/ten.tec.2011.0452
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发表时间:
2012
期刊:
Tissue engineering. Part C, Methods
影响因子:
--
通讯作者:
Jain HV
Jain HV
中科院分区:
--
文献类型:
--
作者:
Jain HV

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组织工程结构和其他具有生物医学应用的固体植入物,例如药物输送装置或生物人工器官,需要氧气 (O2) 才能正常发挥作用。为了更好地了解此类设备的血管整合,我们最近开发了一种包含 O2 敏感晶体的新型模型传感器,该传感器由受纳米多孔过滤器限制的聚合物胶囊组成。该传感器被植入单独的水凝胶(对照)或嵌入小鼠 CD117/c-kit+ 骨髓祖细胞的水凝胶的小鼠中,以刺激植入物周围的新血管形成。该传感器使用无创电子顺磁共振信号测量提供局部氧分压 (pO2)。在 10 周内,细胞治疗组的种植体周围氧合水平始终高于对照组。为了对这些实验观察结果提供机械解释,我们在本文中提出了一个数学模型,该模型被表述为耦合偏微分方程组,用于模拟种植体周围血管化。在对照情况下,血管形成被认为是异物反应的结果,而在细胞治疗情况下,响应干细胞产生的旁分泌刺激的脂肪生成被认为诱导新血管形成。该模型通过将局部 pO2 的数值预测与植入传感器的测量值进行拟合来验证。然后该模型用于进一步研究使用干细胞治疗增强生物医学植入物血管整合的潜力。因此,我们展示了如何使用数学模型与实验相结合来推断对照和干细胞治疗病例中生物医学植入物周围的脉管系统如何发育。
Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O2) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O2-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O2pressure (pO2) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO2to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.
平面组织工程生物人工器官中的氧气和菊粉传输测量。
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