Biology subjects

Midekssa, F. S.

Publications and source records attributed to Midekssa, F. S..

3 recordsLinked to original sources

bioRxiv2026

Filling the Void: Rapid Revascularization via Vasculogenic Assembly in Semi-synthetic Granular Hydrogel Grafts

Rapid revascularization is critical to tissue graft survival, as delayed reperfusion drives tissue ischemia and compromises cell viability and graft function. Although bulk hydrogels have been explored for promoting vessel formation, vascularization remains too slow to prevent ischemic injury to grafted tissues, highlighting the need for biomaterial platforms that accelerate graft revascularization and reperfusion. In this study, we present granular hydrogel composites (GHCs), where interstitial space is filled with fibrin and collagen to provide a vasculogenic matrix environment. GHCs supported the assembly of embedded endothelial cells into interconnected, lumenized networks in vitro which anastomosed with host vasculature and were systemically perfused 7 days after implantation. Careful optimization studies revealed that GHCs formed from covalently interlinked, RGD-functionalized microgels of 115 {micro}m diameter best supported vascular network formation in vitro and intravascular blood perfusion in vivo. To test the utility of GHCs for the vascular integration of a demanding and therapeutically relevant parenchymal tissue, GHC-based ovarian tissue grafts were implanted in a murine xenograft model and successfully connected to host vasculature, restoring blood flow to embedded human ovarian tissues within 10 days post-implantation. Notably, endothelial cells seeded within GHCs formed viable vasculature without pre-culture. This work establishes GHCs as a biomaterial platform to rapidly connect parenchymal tissues to host vasculature, with broad translational potential across engineered tissue grafting applications.

bioengineering↗

bioRxiv2024

Clickable PEG-norbornene microgels support suspension bioprinting and microvascular assembly

The development of perfusable and multiscale vascular networks remains one of the largest challenges in tissue engineering. As such, there is a need for the creation of customizable and facile methods to produce robustly vascularized constructs. In this study, secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads were produced and evaluated for their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature. The clickable PEGNB microbead slurry exhibited mechanical behavior suitable for suspension bioprinting of sacrificial bioinks, could be UV crosslinked into a granular construct post-print, and withstood evacuation of the bioink and subsequent perfusion of the patterned void space. Endothelial and stromal cells co-embedded within jammed RGD-modified PEGNB microbead slurries assembled into capillary-scale vasculature after secondary crosslinking of the beads into granular constructs, with endothelial tubules forming within the interstitial space between microbeads and supported by the perivascular association of the stromal cells. Microvascular self-assembly was not impacted by printing sacrificial bioinks into the cell-laden microbead support bath before UV crosslinking. Collectively, these results demonstrate that clickable PEGNB microbeads are a versatile substrate for both suspension printing and microvascular culture and may be the foundation for a promising methodology to engineer hierarchical vasculature.

bioengineering↗

bioRxiv2024

Local photo-crosslinking of native tissue matrix regulates cell function

Within most tissues, the extracellular microenvironment provides mechanical cues that guide cell fate and function. Changes in the extracellular matrix such as aberrant deposition, densification and increased crosslinking are hallmarks of late-stage fibrotic diseases that often lead to organ dysfunction. Biomaterials have been widely used to mimic the mechanical properties of the fibrotic matrix and study cell function. However, the initiation of fibrosis has largely been overlooked, due to the challenges in recapitulating early fibrotic lesions within the native extracellular microenvironment. Using visible light mediated photochemistry, we induced local crosslinking and stiffening of extracellular matrix proteins within ex vivo murine and human tissue. In ex vivo lung tissue of epithelial cell lineage-traced mice, local matrix crosslinking mimicked early fibrotic lesions that increased alveolar epithelial cell spreading, differentiation and extracellular matrix remodeling. However, inhibition of cytoskeletal tension or integrin engagement reduced epithelial cell spreading and differentiation, resulting in alveolar epithelial cell dedifferentiation and reduced extracellular matrix deposition. Our findings emphasize the role of local extracellular matrix crosslinking and remodeling in early-stage tissue fibrosis and have implications for ex vivo disease modeling and applications to other tissues.

bioengineering↗