Integration and Regression of Implanted Engineered Human Vascular Networks During Deep Wound Healing

Abstract

The ability of vascularized constructs to integrate with tissues may depend on the kinetics and stability of vascular structure development. This study assessed the functionality and durability of engineered human vasculatures from endothelial progenitors when implanted in a mouse deep burn-wound model. Human vascular networks, derived from endothelial colony-forming cells in hyaluronic acid hydrogels, were transplanted into third-degree burns. On day 3 following transplantation, macrophages rapidly degraded the hydrogel during a period of inflammation; through the transitions from inflammation to proliferation (days 5-7), the host's vasculatures infiltrated the construct, connecting with the human vessels within the wound area. The growth of mouse vessels near the wound area supported further integration with the implanted human vasculatures. During this period, the majority of the vessels (ϳ60%) in the treated wound area were human. Although no increase in the density of human vessels was detected during the proliferative phase, they temporarily increased in size. This growth peaked at day 7, the middle of the proliferation stage, and then decreased by the end of the proliferation stage. As the wound reached the remodeling period during the second week after transplantation, the vasculatures including the transplanted human vessels generally regressed, and few microvessels, wrapped by mouse smooth muscle cells and with a vessel area less than 200 m 2 (including the human ones), remained in the healed wound. Overall, this study offers useful insights for the development of vascularization strategies for wound healing and ischemic conditions, for tissue-engineered constructs, and for tissue regeneration. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:297-306

Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization

“…S14) according to ANOVA analysis. Collectively these results indicate that the treatment with high-dose peptide hydrogel leads to sufficient angiogenesis to drive the rapid formation of granulation tissue without the massive vessel overgrowth early on followed by a pronounced vessel regression that is often reported with treatments that overstimulate early angiogenesis (32)(33)(34).…”

Introduction to cell–hydrogel mechanosensing

“…These types of hydrogel are particularly useful in examining cellular behaviour owing to their biocompatibility, biodegradability and biofunctionality [68]. cornea agarose-fibrin [29] alginate-gelatin nanofibre [163] collagen [146,149,150] collagen-PLGLA nanofibre [160] alginate [34] cellulose [35] heparin [36] alginate-hyaluronic acid [33] collagen [190] collagen-chitosan [32] dextran [30,31] hyaluronic acid [44] alginate [27] collagen [23,24] dextran [25] gelatin [26] collagen [17,97] fibrin [37] agarose [51,175,179,196] alginate [126] chitosan [20,50] fibrin [42,51] gellan gum [22,51] hyaluronic acid [110] PEG [60] A key factor when examining cell-material mechano-interactions is the mechanisms of cell adhesion to the hydrogel. Cell surface receptors such as integrins bind to ligands within the hydrogel if such adhesion sites exist.…”

“…The types of hydrogels used in regenerative medicine can broadly be split into two categories: natural polymer hydrogels and synthetic polymer hydrogels [14]. Among the most extensively used natural hydrogels that have been under examination for use in tissue engineering and regenerative medicine are collagen [38][39][40], fibrin [41][42][43], hyaluronic acid [44][45][46], alginate [47,48], chitosan [49,50] and agarose [51][52][53]. These hydrogels differ in polymer structure (figure 1), ability to retain water, availability of binding sites and mechanical characteristics.…”

Endothelial Network Formation Within Human Tissue-Engineered Skeletal Muscle

“…39 It remains to be seen though if the type of endothelial cells, which are used in vitro, is a critical factor once the construct is implanted since the implanted endothelial network may be replaced by the host. Engineered human vascular networks, which were transplanted into third-degree burns, connected with the host vessels during the first week, but during a remodeling phase in the second week after transplantation, the transplanted vessels regressed 40 and were replaced by host vessels. Transformation into mature blood vessels occurs through an inflammation-mediated process of vascular remodeling.…”