A Mathematical Framework to Study the Effects of Growth Factor Influences on Fracture Healing

✍ Scribed by ALICIA BAILÓN-PLAZA; MARJOLEIN C.H. VAN DER MEULEN

• Publisher: Elsevier Science
• Year: 2001
• Tongue: English
• Weight: 678 KB
• Volume: 212
• Category: Article
• ISSN: 0022-5193
• DOI: 10.1006/jtbi.2001.2372

✦ Synopsis

During fracture healing, multipotential stem cells di!erentiate into specialized cells responsible for producing the di!erent tissues involved in the bone regeneration process. This cell di!erentiation 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 twodimensional mathematical model of the bone healing process for moderate fracture gap sizes and fracture stability. The in#ammatory and tissue regeneration stages of healing are simulated by modeling mesenchymal cell migration; mesenchymal cell, chondrocyte and osteoblast proliferation and di!erentiation, and extracellular matrix synthesis and degradation over time. The e!ects of two generic growth factors on cell di!erentiation are based on the experimentally studied chondrogenic and osteogenic e!ects of bone morphogenetic proteins-2 and 4 and transforming growth factor--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 ossi"cation and successful healing. This temporo-spatial model of fracture healing is the "rst model to consider the e!ects 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.