(595e) Guest-Host Supramolecular Assembly of Injectable Hydrogel Nanofibers for 3D Cell Encapsulation and Pelvic Organ Prolapse Repair

The fibrous architecture of the extracellular matrix (ECM) is recognized as an integral regulator of cell function. However, there is an unmet need to develop mechanically robust biomaterials mimicking nanofibrous tissue topography that are also injectable to enable minimally invasive delivery. In particular, there is an urgent clinical need for innovation in the field of prolapse surgery and tissue engineering approaches to augment prolapse repair. Pelvic organ prolapse (POP) affects millions of women worldwide yet a common surgical repair option, the uterosacral ligament suspension (USLS), is plagued by a relatively high failure rate of up to 30%. The mechanism of the high failure rate of the USLS repair surgery is largely believed to be due to the non-native interface between the smooth muscle of the organ (vagina) and the fibrous architecture of the ligament. Although innovative tissue engineering approaches are emerging to advance and augment fibrous tissue repair, the vast majority of these strategies have either not achieved long-term success, or have not focused on POP or ligament attachment in a clinical space. In this study we have developed a 3D fibrous hydrogel composed of supramolecularly-assembled hyaluronic acid (HA) nanofibers that exhibits mechanical integrity, shear-thinning, rapid self-healing, and cytocompatibility.

In the development of the material, HA was modified with methacrylates to permit fiber photocrosslinking following electrospinning and either ‘guest’ adamantane or ‘host’ β-cyclodextrin groups to guide supramolecular fibrous hydrogel assembly. Analysis of the hydrogel fiber rheological properties showed that the mixed guest-host fibrous hydrogel was more mechanically robust (6.6 ± 2.0 kPa, storage modulus (Gʹ)) than unmixed guest hydrogel fibers (1.0 ± 0.1 kPa) or host hydrogel fibers (1.1 ± 0.1 kPa) separately (Figure A). The reversible nature of the guest-host supramolecular interactions also allowed for shear-thinning and self-healing behavior as demonstrated by cyclic deformation testing and subsequent injection for cell studies. Human mesenchymal stromal cells (hMSCs) encapsulated in fibrous hydrogels demonstrated satisfactory viability following injection and after seven days of culture (> 85%). Encapsulated hMSCs were more spread and elongated when cultured in viscoelastic guest-host hydrogels compared to non-fibrous elastic controls, with hMSCs also showing significantly decreased circularity in fibrous guest-host hydrogels compared to non-fibrous guest-host hydrogels (Figure B). Together, these data highlight the potential of this injectable 3D fibrous hydrogel platform for cell and tissue engineering applications requiring minimally invasive delivery. Ongoing work is assessing the biocompatibility and therapeutic efficacy of the biomaterial scaffold in a rat model (Figure C) of USLS.