A mathematical framework to study the effects of growth factor influences on fracture healing
A mathematical framework to study the effects of growth factor influences on fracture healing
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DOI：
10.1006/jtbi.2001.2372
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发表时间：
2001-09-21
影响因子：
2
通讯作者：
van der Meulen, MCH
中科院分区：
文献类型：
--
作者：
Bailón-Plaza, A;van der Meulen, MCH
在骨折愈合过程中，多能干细胞分化成专门的细胞，负责产生参与骨再生过程的不同组织。这种细胞分化已被证明受到局部表达的生长因子的调节。需要了解其监管机制的细节。在这项工作中，我们提出了一个针对中等骨折间隙大小和骨折稳定性的骨愈合过程的二维数学模型。通过对间充质细胞迁移建模来模拟愈合的炎症和组织再生阶段；随着时间的推移，间充质细胞、软骨细胞和成骨细胞的增殖和分化，以及细胞外基质的合成和降解。两种通用生长因子对细胞分化的影响分别基于通过实验研究的骨形态发生蛋白-2和4以及转化生长因子-β-1的软骨形成和成骨作用。该模型成功地模拟了愈合过程，并预测成骨细胞产生成骨生长因子的速率和受伤时生长因子初始释放的持续时间是完全骨化和成功愈合的特别重要的参数。这种骨折愈合的时空模型是第一个考虑生长因子影响的模型。它将帮助我们了解骨再生中涉及的调节机制，并提供一个数学框架来设计实验和了解病理状况。 (C) 2001 年学术出版社。
During fracture healing, multipotential stem cells differentiate into specialized cells responsible for producing the different tissues involved in the bone regeneration process. This cell differentiation has been shown to be regulated by locally expressed growth factors. The details of their regulatory mechanisms need to be understood. In this work, we present a two-dimensional mathematical model of the bone healing process for moderate fracture gap sizes and fracture stability. The inflammatory and tissue regeneration stages of healing are simulated by modeling mesenchymal cell migration; mesenchymal cell, chondrocyte and osteoblast proliferation and differentiation, and extracellular matrix synthesis and degradation over time. The effects of two generic growth factors on cell differentiation are based on the experimentally studied chondrogenic and osteogenic effects of bone morphogenetic proteins-2 and 4 and transforming growth factor-beta -1, respectively. The model successfully simulates the progression of healing and predicts that the rate of osteogenic growth factor production by osteoblasts and the duration of the initial release of growth factors upon injury are particularly important parameters for complete ossification and successful healing. This temporo-spatial model of fracture healing is the first model to consider the effects of growth factors. It will help us understand the regulatory mechanisms involved in bone regeneration and provides a mathematical framework with which to design experiments and understand pathological conditions. (C) 2001 Academic Press.