Flexible shape-memory scaffold for minimally invasive delivery of functional tissues

Abstract

Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold's shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.

Injectable Hyaluronic Acid-co-Gelatin Cryogels for Tissue-Engineering Applications

“…Ideally, scaffolds should promote cell–material interactions, support the movement of nutrients and waste, possess good biocompatibility, and have appropriate mechanical properties [49]. However, their placement in the body remains a challenge and often requires performing an invasive surgical procedure [73]. Previously developed injectable strategies that rely on in situ gelation post-injection often face limitations such as inflammation or poor biophysical properties [74].…”

Citrate chemistry and biology for biomaterials design

“…For example, by advanced new 3D stamping technique, POMC has recently been fabricated into a AngioChip scaffold with built-in branching microchannel networks to generate perusable vasculature enabling direct surgical anastomosis [20]. Meanwhile, POMC enables the microfabricated lattice design into scaffold with shape memory, using a combination of soft-lithography and injection molding, for functional tissue delivery via injection [21]. Notably, incorporation of maleic anhydride in POMC also enabled the ultra-finely tuning of optical properties to possess a higher refractive index than POC with an index difference of ~0.003, comparable to that between the cladding and the core of conventional silica optical fibers.…”

“…More importantly, together with either human embronic stem cells (hESC) derived or neonatal rate cardiomyocytes, AngioChip scaffolds confer the engineering of fully endothelialized cardiac tissues with the thickness of 1.75–2 mm, with high cell viability under perfusion, and with the capability of surgical anastomosis to host vasculature [20]. In another study, POMC, when fabricated into injectable cardiac patches with microfabricated lattice design and loaded with cardiomyocytes, have shown to significantly improve cardiac function following myocardial infarction in a rat, serving as a flexible scaffold for invasive delivery of functional cardiac tissues [21]. …”

Turning regenerative technologies into treatment to repair myocardial injuries

“…Indeed, cardiac patches performed with these flexible materials may significantly improve cardiac function and are promising for clinical translation. 129…”