Implantable Therapeutic Reservoir Systems for Diverse Clinical Applications in Large Animal Models

• Published in: Advanced healthcare materials 2020-06, Vol.9 (11), p.e2000305-n/a
• Main Authors: Duffy, Garry P., Robinson, Scott T., O'Connor, Raymond, Wylie, Robert, Mauerhofer, Ciaran, Bellavia, Gabriella, Straino, Stefania, Cianfarani, Francesca, Mendez, Keegan, Beatty, Rachel, Levey, Ruth, O'Sullivan, Janice, McDonough, Liam, Kelly, Helena, Roche, Ellen T., Dolan, Eimear B.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Arrays; Cargo; cell and drug delivery; Cell survival; Fixation; Humans; Hydrogels; Laparoscopy; minimally invasive therapeutics; Models, Animal; Polymers; Prostheses and Implants; Refilling; Regenerative Medicine; regional and repeated delivery; Shear thinning (liquids); Soft tissues; Stem cells; Therapeutic applications; therapeutic reservoirs; Tissue engineering
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202000305

Regenerative medicine approaches, specifically stem cell technologies, have demonstrated significant potential to treat a diverse array of pathologies. However, such approaches have resulted in a modest clinical benefit, which may be attributed to poor cell retention/survival at the disease site. A delivery system that facilitates regional and repeated delivery to target tissues can provide enhanced clinical efficacy of cell therapies when localized delivery of high doses of cells is required. In this study, a new regenerative reservoir platform (Regenervoir) is described for use in large animal models, with relevance to cardiac, abdominal, and soft tissue pathologies. Regenervoir incorporates multiple novel design features essential for clinical translation, with a focus on scalability, mechanism of delivery, fixation to target tissue, and filling/refilling with a therapeutic cargo, and is demonstrated in an array of clinical applications that are easily translated to human studies. Regenervoir consists of a porous reservoir fabricated from a single material, a flexible thermoplastic polymer, capable of delivering cargo via fill lines to target tissues. A radiopaque shear thinning hydrogel can be delivered to the therapy reservoir and multiple fixation methods (laparoscopic tacks and cyanoacrylate bioadhesive) can be used to secure Regenervoir to target tissues through a minimally invasive approach. In this study, a new regenerative reservoir platform (Regenervoir) is described for use in large animal models that are easily translated to human studies, with relevance to cardiac, abdominal, and soft tissue pathologies. Regenervoir incorporates multiple novel design features essential for clinical translation, with a focus on scalability, mechanism of delivery, fixation, and filling/refilling with a therapeutic cargo.