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

In tissue engineering research, generating constructs with an adequate extent of clinical applications remains a major challenge. In this context, rapid blood vessel ingrowth in the transplanted tissue engineering constructs is the key factor for successful incorporation. To accelerate the microvascular development in engineered tissues, we preincubated osteoblast-like cells as well as mesenchymal stem cells or a combination of both cell types in Matrigel-filled PLGA scaffolds before transplantation into the dorsal skinfold chambers of balb/c mice. By the use of preincubated mesenchymal stem cells, a significantly accelerated angiogenesis was achieved. Compared with previous studies that showed a decisive increase of vascularization on day 6 after the implantation, we were able to halve this period and achieve explicitly denser microvascular networks 3 days after transplantation of the tissue engineering constructs. Thereby, the inflammatory host tissue response was acceptable and low, comparable with former investigations. A co- incubation of osteoblast-like cells and stem cells showed no additive effect on the density of the newly formed microvascular network. Preincubation of mesenchymal stem cells in Matrigel is a promising approach to develop rapid microvascular growth into tissue engineering constructs. After the implantation into the host organism, scaffolds comprising stem cells generate microvascular capillary-like structures exceptionally fast. Thereby, transplanted stem cells likely differentiate into vessel-associated cells. For this reason, preincubation of mesenchymal stem cells in nutrient solutions supporting different steps of angiogenesis provides a technique to promote the routine use of tissue engineering in the clinic. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1652–1662, 2014.