Vascular Pedicle and Microchannels: Simple Methods Toward Effective In Vivo Vascularization of 3D Scaffolds

Abstract

Poor vascularization remains a key limiting factor in translating advances in tissue engineering to clinical applications. Vascular pedicles (large arteries and veins) isolated in plastic chambers are known to sprout an extensive capillary network. This study examined the effect vascular pedicles and scaffold architecture have on vascularization and tissue integration of implanted silk scaffolds. Porous silk scaffolds with or without microchannels are manufactured to support implantation of a central vascular pedicle, without a chamber, implanted in the groin of Sprague Dawley rats, and assessed morphologically and morphometrically at 2 and 6 weeks. At both time points, blood vessels, connective tissue, and an inflammatory response infiltrate all scaffold pores externally, and centrally when a vascular pedicle is implanted. At week 2, vascular pedicles significantly increase the degree of scaffold tissue infiltration, and both the pedicle and the scaffold microchannels significantly increase vascular volume and vascular density. Interestingly, microchannels contribute to increased scaffold vascularity without affecting overall tissue infiltration, suggesting a direct effect of biomaterial architecture on vascularization. The inclusion of pedicles and microchannels are simple and effective proangiogenic techniques for engineering thick tissue constructs as both increase the speed of construct vascularization in the early weeks post in vivo implantation.

Applications of Engineering Techniques in Microvasculature Design

“…Micropatterning for vascularization involves the subtraction of predefined patterns within the engineered matrix to create microchannels that resemble a vascular network. It can be classified into two modalities: micromolding (18,19) and laser degradation (20). Fine-tuned micropatterns on the scaffold provides spatial cues allowing for EC attachment and subsequent 3D-tube formation.…”

“…For example, Teflon coated wires with a diameter of 500 µm incorporated into a silk-based scaffold act as a mold for fabricating microchannels within a thick silk scaffold (7 mm). These channels allowed vascularization within 2 weeks postimplantation in mice (19). However, a simple tubular mold cannot capture the complexity of natural microvasculature within the tissue.…”

Silk fibroin photo-lyogels containing microchannels as a biomaterial platform for in situ tissue engineering

“…15,16 A few reports of silk based lyogels have been published and it has been demonstrated that the crosslinked nature of the starting protein network results in unique physicochemical properties compared to lyophilized sponges made by lyophilizing uncrosslinked silk solution. 14,[16][17][18][19] While lyophilized silk sponges have been widely explored and evaluated for applications such as soft tissue, [20][21][22] intervertebral disc, 23 and cardiovascular tissue [24][25][26] augmentation and regeneration, platelet production, 27 and drug delivery, 28,29 silk lyogels are less well characterized. In particular, the properties of silk lyogels made from di-tyrosine crosslinked silk networks have not been explored to date.…”

Neovascularization of engineered tissues for clinical translation: Where we are, where we should be?

“… 28 Neovascularization is a delayed process (almost 15 days) and depends on graft thickness. Whereas inosculation, the formation of functional connections with host capillaries, 29 is a thickness independent and fast process (<4 days) [ Fig. 3(a) ].…”