The Development of Vascularised 3D Tissue Engineering Constructs

Despite significant advances in tissue engineering, the translation of these
developments to clinical applications is limited. One of the major reasons that
this is the case is that it is currently not possible to create engineered tissues
which are vascularised suitable for transplantation. Vasculature is essential for
the development of clinically relevant engineered tissues to facilitate the mass
transport of oxygen and nutrients to cells within the tissue and removal of waste
products. Furthermore, vasculature is essential for the integration of the tissue
into the hosts circulatory system during transplantation to ensure the survival of
the transplant. Current vascularisation strategies have been met with limited
success with two of the key challenges being identifying an optimal cell source
for the formation of vasculature and a scaffold material for supporting vascular
growth.
This study set out to explore the potential of dental pulp stem cells (DPSCs) as
an easily accessible adult mesenchymal stem cell with the potential for
endothelial differentiation. Additionally, the self-assembling peptide P11-4 was
investigated as a possible scaffold material to support vascularisation due to its
tuneable properties which allow it to be used in mimicking the extracellular
matrix of several tissues.
DPSCs were induced to differentiate into an endothelial phenotype using
endothelial cell culture media containing a number of essential growth factors
required for endothelial cell function and survival. Endothelial differentiation
was confirmed by the significant increase in the expression of endothelial
markers CD31 and VEGFR2 at both the gene and protein expression level after 5
and 10 days of differentiation. Furthermore, differentiated cells demonstrated
endothelial-like cell function during Matrigel tube formation assays, forming
cellular networks comparable to those of human umbilical vein endothelial cells
(HUVEC). Optimised P11-4 hydrogels were able to support HUVEC network formation in 3D
culture, however endothelial-like cells derived from DPSCs did not interact with
the gel in a comparable way.
This study provides evidence for the first time that P11-4 possesses proangiogenic
properties and has the capacity to support vascular like growth, though further
modifications to the peptide are needed to improve its suitability for clinical
applications. This research also confirms reports in other research that DPSCs
have the potential to differentiate into endothelial-like cells, though
improvements are needed to optimise their function for the creation of
vascularised 3D tissue engineering constructs.