Wagner, W. R. | bioRxiv Science

bioRxiv2026

Organotypic artery-graft culture enables label-free multiphoton tracking of remodeling that links to long-term graft microarchitecture

The long-term performance of tissue-engineered scaffolds, particularly small-diameter vascular grafts, is shaped by remodeling events at the tissue-graft interface, yet these processes remain difficult to resolve longitudinally and at microstructural resolution in conventional implantation models. Here we develop an organotypic artery-graft model that preserves cylindrical vessel geometry and enables non-destructive label-free multiphoton monitoring of interface remodeling. Using second harmonic generation and two-photon excited fluorescence, we capture evolving fibrillar collagen architecture and cellularization over time, demonstrate compatibility with multiple biomaterial classes, and show integration with rat and mouse explants, live-cell dyes, and fluorescent reporter tissues. The platform resolved distinct remodeling responses to transforming growth factor-{beta} isoforms (TGF-{beta}1, -{beta}2, and -{beta}3), with differential shifts in collagen-fiber distributions, accompanied by changes in matrix-remodeling and contractile gene expression. Across two graft designs, culture-derived remodeling phenotypes, collagen fiber distributions, and initial trajectories agreed with those observed in long-term 6-month interpositional explants. Together, these results establish an accessible intermediate platform for interrogating artery-graft remodeling, tracking these trajectories, and prioritizing graft designs through interface-resolved outcomes before and alongside animal implantation studies.

bioengineering↗

bioRxiv2024

Intervening to preserve function in ischemic cardiomyopathy with a porous hydrogel and extracellular matrix composite in a rat myocardial infarction model

A variety of hydrogels have been developed for intramyocardial injection therapy after myocardial infarction. Some of these biomaterials have incorporated bioactive substances that promote local tissue regeneration and integration, while others have emphasized the mechanical role of the injectate in providing functional benefit. In this study, we incorporated two bioactive features, porosity, and extracellular matrix derived hydrogel (ECM), into a mechanically optimized, thermoresponsive, degradable hydrogel (poly(N-isopropylacrylamide-co-N-vinylpyrrolidone-co-MAPLA) copolymer) and evaluated whether injection of this biomaterial could abrogate the remodeling process in a rat ischemic cardiomyopathy model. After myocardial infarction by coronary artery ligation, rats were randomly divided into four groups: group NP (non-porous hydrogel) without either ECM or porosity, group PM (porous hydrogel) from the same synthetic copolymer with mannitol beads as porogens, and group PME with porosity and ECM digest added to the synthetic copolymer. A group with PBS injection alone served as a control. Intramyocardial injections were made 3 days after myocardial infarction. Serial echocardiography was assessed over time, and histological assessments were performed eight weeks after infarction. Results demonstrated improved echocardiographic function and neovascularization in the PME group compared to the other hydrogels and PBS injection. The PME group also demonstrated significant improvement in LV geometry and macrophage polarization (towards M2) compared to the PBS group, whereas these differences were not observed in the NP or PM groups versus the control. These results demonstrate that further functional improvement may be achieved in hydrogel injection therapy for ischemic cardiomyopathy by incorporating porosity and ECM digest, representing a combination of mechanical and biological effects.

bioengineering↗