Comparably accelerated vascularization by preincorporation of aortic fragments and mesenchymal stem cells in implanted tissue engineering constructs

Abstract

The demanding need for tissue replacement resulted in manifold approaches for the construction of different tissues. One common problem which hampers the clinical usage of tissue engineering constructs is a limited vascularization. In an attempt to accelerate the vascularization of tissue engineering constructs we compared the usage of bone marrow mesenchymal stem cells (bmMSCs) and fragments derived from the aorta in vivo. Tissue engineering constructs composed of PLGA scaffolds containing Matrigel (n = 8), aortic fragments embedded in Matrigel (n = 8), bmMSCs embedded in Matrigel (n = 8), and aortic fragments embedded in Matrigel combined with bmMSCs (n = 8) were implanted into dorsal skinfold chambers of balb/c mice and analyzed repetitively over 14 days. In all groups a weak inflammatory response was transiently apparent. Vascularization was significantly (p = 0.05) accelerated in bmMSC and aortic fragments containing constructs compared with Matrigel alone, demonstrated by a distinctly increased microvascular density throughout the whole experiment. The combination of bmMSCs and aortic fragments showed no additional effect compared with bmMSCs and aortic fragments alone. The accelerated vascularization and microvascular density of tissue engineering constructs triggered by bmMSCs and aortic fragments is comparable. Thus aortic fragments provide a new promising source for clinical relevant tissue engineering constructs.

Decelerated vascularization in tissue-engineered constructs in association with diabetes mellitus in vivo

“…This observation applied to the scaffolds seeded with organ-specific cells (OLCs) or undifferentiated progenitor cells (bmMSCs) as well as to the non-vitalized scaffolds. The cell-seeded scaffolds showed a significantly higher number of capillary-like structures within their particular group (diabetic and non-diabetic) from day 6 after transplantation, a result which is in line with previous studies [8,32].…”

“…With regards to the inflammatory host tissue response, diabetic mice and controls showed comparable results to earlier studies concerning the analyzed parameters (rolling and adherent leukocytes, macromolecular leakage) [4,8,32]. The moderate increase in these values after implantation of all types of scaffolds at day 3 are in line with other investigations, showing a local transient inflammatory tissue response after implantation of foreign materials [8,38].…”

“…For in vivo microscopic analyses, they were applied in association with the dorsal skinfold chamber because of the excellent comparability with previous investigations [3,4,8,32]. Growth factors were not used in the present study, although several successful applications in diabetic animals have been described [39].…”

Prolongated Survival of Osteoblast-Like Cells on Biodegradable Scaffolds by Heat Shock Preconditioning

“…31 We showed in vivo that the main task for tissue engineering is not to produce more capillaries, but to reduce the time span until the maximum capillary density is reached. 14,32 Therefore, the main task for us was to enhance cell survival until this maximum capillary density was reached. The effect of preconditioning caused a significantly higher survival of the seeded OLC by increasing stress tolerance of the seeded cells.…”

Accelerating the early angiogenesis of tissue engineering constructs in vivo by the use of stem cells cultured in matrigel

“…Mesenchymal stem cells are also characterized by their tube‐forming ability on Matrigel and excel at developing a capillary network when incubated in a 3D Matrigel matrix . Recently, bmMSCs in combination with Matrigel have been examined in a tissue engineering study, without preincubation of the cells . For both bmMSCs and OLCs, in vitro tests of vascular differentiation capacities have been described in detail .…”