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Engineering Hierarchical Microvasculature: Microgel Size Regulates Microvascular Maturation in Granular Hydrogel Scaffolds
MohammadHossein Asgardoon
*1, Saman Zavari
2, Jenn Park
1, Neekita Jikaria
1, Mary Landmesser
1, Amir Sheikhi
2, Dino Ravnic
11Surgery, Penn State University, Hershey, PA; 2Chemical Engineering, Penn State University, University Park, PA
Background:Tissue engineering represents the next era of reconstructive surgery. Native tissue flaps are nourished through a mature hierarchical microvasculature that is characterized by variable intracapillary (IC) distances. Change in IC distance allows for controllable perfusion and the matching of oxygen with metabolic demand. Recently we have shown that granular hydrogel scaffolds (GHS) that are composed of size-tunable microgels, can be used to achieve controllable IC distances. However, it is unknown how this translates to microvascular maturation, also necessary for optimal oxygen matching. We hypothesize that by modulating microgel size and interface, the GHS microvasculature will display compliance in maturation as assessed by permeability.
Methods:Gelatin methacrylate microgels with diameters of 25-, 85-, 180-μm ( small, medium, large) were fabricated and assembled into GHS (16×10×3 mm) via centrifugation and interparticle crosslinking to generate distinct microgel regions: small, medium, large, small-medium (S-M), small-large (S-L), and medium-large (M-L) as shown in
Fig.1A. Scaffolds were implanted subcutaneously in rats (n=3/group). On day 14, in vivo permeability assays were performed using concurrent intravascular injection of FITC-dextran (2MDa) and Evans Blue (EB; 0.96 kg/mol). A permeability index (PI) was calculated as EB/FITC stained area. Analysis was performed using ImageJ and GraphPad Prism.
Results:Medium sized microgels showed the lowest permeability compared to small and large microgels. Among interface regions, S-M interfaces showed the lowest permeability, whereas abrupt size mismatches (M-L, S-L) showed progressively increased leakage (M-L > S-L >> S-M) (
Fig.1B-C).
Conclusions:Microgel size and interface design regulate microvascular maturation in GHS. Gradual transitions in microgel size, particularly at S-M interfaces, promote microvascular maturation, whereas abrupt size mismatches lead to a leaky vasculature. These findings establish hierarchical microgel patterning as a key strategy for engineering a mature microvasculature.
Models adjusted for BMI, tissue expander size, and axillary irradiation. OR > 1 indicates higher odds with early exchange.
Back to 2026 Abstracts
Models adjusted for BMI, tissue expander size, and axillary irradiation. OR > 1 indicates higher odds with early exchange.
