Biomedical Engineering Reference
In-Depth Information
moving through its impact on tissue engineering and bone regeneration, and
ending with repair. Furthermore, we also describe the most recent in-silico models
proposed to simulate the vascular network within bone constructs. Finally, discrete
as well as continuum approaches are analyzed from a computational perspective
and applied to three distinct phenomena: wound healing, distraction osteogenesis
and individual cell migration in 3D.
1 Introduction
Angiogenesis, i.e. the formation of new blood vessels from the existing vasculature
is essential for complex biological phenomena in healthy and diseased individuals,
including tissue reconstruction [
53
] and tumor growth [
36
]. In the case of tissue
reconstruction, the ability of bone defects (resulting from trauma, congenital
deficiency, infection or tumor resection) to heal depends on the ability of new blood
vessels to proliferate from surrounding vessels. Since bone defects represent a
medical and socioeconomical challenge [
65
] it is very important to understand the
role of the vascular system in bone regeneration. Therefore, particular attention is
paid to surgical techniques to bridge bone injuries. Different types of biomaterials,
internal plates and fixation devices are applied according to the reconstruction
interests but in all cases vascular supply is crucial. Within the field of tissue
engineering and in the case of large skeletal defects, capillary growth appears to be
particularly complex, possibly because of the slow rate of infiltration of blood
vessels into the scaffold. It makes the process insufficient to provide adequate
nutrients to the cells in the interior of large constructs, which results in peripheral
tissue formation and central scaffold necrosis [
65
,
83
,
86
]. In addition, the in vivo
studies on bioengineered tissue vascularization have not been performed until
recently and are focus of intense research activity nowadays. In contrast, the robust
nature of bone induction in fracture healing and distraction osteogenesis has made it
an important system to study the role of angiogenesis in bone regeneration [
32
,
56
,
75
]. Therefore this review addresses the role of the vascular network in these well
defined and controlled processes. It aims to cover the connection between vascu-
larization and bone, starting with the biology of vascular ingrowth, moving through
its impact on tissue engineering and bone regeneration, and ending with repair.
Furthermore, we will review the most recent in-silico models proposed to simulate
the vascular network within bone constructs. Mathematical as well as algorithmic
discrete approaches, which are implemented through continuous representations
and operational descriptions respectively, will be described.
2 Vascular Ingrowth
Blood vessels form from either de novo, via vasculogenesis or by sprouting or
splitting of existing blood vessels via angiogenesis. Angiogenesis may be cate-
gorized into angiogenic remodelling and sprouting [
125
]. In the former, an initial
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