Cell Proliferation and Oxygen Diffusion in a Vascularising Scaffold

Abstract

The supply of oxygen to proliferating cells within a scaffold is a key factor for the successful building of new tissue in soft tissue engineering applications. A recent in vivo model, where an arteriovenous loop is placed in a scaffold, allows a vascularising network to form within a scaffold, establishing an oxygen source within, rather than external, to the scaffold. A one-dimensional model of oxygen concentration, cell proliferation and cell migration inside such a vascularising scaffold is developed and investigated. In addition, a vascularisation model is presented, which supports a vascularisation front which moves at a constant speed. The effects of vascular growth, homogenous and heterogenous seeding, diffusion of cells and critical hypoxic oxygen concentration are considered. For homogenous seeding, a relationship between the speed of the vascular front and a parameter defining the rate of oxygen diffusion relative to the rate of oxygen consumption determines whether a hypoxic region exists at some time. In particular, an estimate of the length of time that a fixed point in the scaffold will remain under hypoxic conditions is determined. For heterogenous seeding, a Fisher-like travelling wave of cells is established behind the vascular front. These findings provide a fundamental understanding of the important interplay between the parameters and allows for a theoretical assessment of a seeding strategy in a vascularising scaffold.

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

“…The limited, peripheral bone tissue formation is mainly due to insufficient nutrient and oxygen delivery and metabolic waste removal within the 3D structure of the scaffolds. 63,64 This is more profound under static culture conditions, where the high cell density on the outer surfaces of the scaffolds may result in diminished nutrient supply to the cells located inside the scaffolds. Consequently, the cells at the center of the constructs would be subjected to nutrient deprivation and ultimately necrosis, which hinders the success of engineered constructs for bone regeneration.…”

Vascularization in Bone Tissue Engineering: Physiology, Current Strategies, Major Hurdles and Future Challenges

“…Diffusion constrains of engineered constructs are already an issue during in vitro culture, in which nutrient transport is only assured to cells on the superficial areas of the scaffold; those cells growing at a greater depth in the construct face nutrient deprivation and ultimately cell death. [9,10] From a clinical point of view this is an important aspect because resection of bone tumors or trauma originate large skeletal defects, which require large segments of implant material to be grafted. Mass transfer in a graft, defined as the in and out movement of molecules, is a phenomenon highly impaired by the thickness of the implant.…”

Mass Transfer Analysis of Growth and Substance Metabolism of NSCs Cultured in Collagen-Based Scaffold In Vitro

“…It is well known that sufficient oxygen supplying can support cell survival and growth; this is especially true in the center of large scaffolds [56][57][58].…”