Decorin-containing collagen hydrogels as dimensionally stable scaffolds to study the effects of compressive mechanical loading on angiogenesis

Abstract

Angiogenesis is a critical component during wound healing, and the process is sensitive to mechanical stimuli. Current in vitro culture environments used to investigate three-dimensional microvascular growth often lack dimensional stability and the ability to withstand compression. We investigated the ability of decorin, a proteoglycan known to modulate collagen fibrillogenesis, incorporated into a collagen hydrogel to increase construct dimensional stability while maintaining vascular growth. Decorin did not affect microvascular growth parameters, while increasing the compressive modulus of collagen gels and significantly reducing the contraction of 3% collagen gels after 16 days in culture.

Effects of BMP‐2 dose and delivery of microvascular fragments on healing of bone defects with concomitant volumetric muscle loss

“…MVF have been shown to improve tissue vascularization and integration; however, this has been primarily demonstrated in subcutaneous implantation, skin flaps, and dermal substitutes, all of which are considerably thinner and thus closer to native vascular sources than the critical size bone defect used here. MVF have also been shown to increase tissue perfusion in VML models when delivered in collagen gel, which allows for sprouting angiogenesis . In this study, while in vitro viability of MVF was maintained in collagen sponge, the multicellular MVF first dissociated to single cells and then reformed networks.…”

“…MVF have also been shown to increase tissue perfusion in VML models when delivered in collagen gel, 21,40 which allows for sprouting angiogenesis. 17,21,41,42 In this study, while in vitro viability of MVF was maintained in collagen sponge, the multicellular MVF first dissociated to single cells and then reformed networks. This is not consistent with the sprouting angiogenesis typically observed within a collagen gel and may have contributed to the lack of effect of MVF on bone healing.…”

“…While collagen sponge is a clinically available BMP‐2 delivery vehicle, it may not be an optimal delivery vehicle for MVF, which are exquisitely sensitive to extracellular matrix properties . Further, MVF exert traction forces on their matrices and can contract collagen hydrogels; cell‐mediated contraction of collagen sponge may have contributed to the more fragmented mineralization observed in the MVF‐treated defects (Fig. C).…”

Mechanical Regulation of Microvascular Angiogenesis

“…Microvascular fragments were obtained through selective filtration to retain multicellular structures between 20-200 µm. The fragments were suspended at a density of 20,000 fragments/mL in 3% collagen gels supplemented with 50 µg/mL decorin (DCN) to improve construct dimensional stability (54). Gels were formed by 15-20 minutes of incubation at 37 °C in custom polycarbonate molds to create gels with a diameter of 5 mm and a height 4 mm.…”

“…Stress relaxation data of decorin-supplemented collagen hydrogels from prior publication were fit to a biphasic constitutive model with a neo-Hookean ellipsoidal fiber distribution solid phase (54). The solid volume fraction was approximated based on the effective specific volume of collagen at 3 mg/mL (56,57).…”