Self‐healing injectable gelatin hydrogels for localized therapeutic cell delivery

Abstract

Self‐healing injectable hydrogel biomaterials uniquely enable precise therapeutic deposition and deployment at specific bodily locations through versatile and minimally invasive processes that can preserve cargo integrity and cell viability. Despite the distinct advantages that injectable hydrogels offer in tissue engineering and therapeutic delivery, exceptionally few have been created using components naturally present in the cellular niche. In this work, we introduce a shear‐thinning hydrogel based on guest‐host complexation of gelatin. As a biocompatible, biodegradable, and nonimmunogenic biopolymer derived from the most abundant extracellular matrix protein (collagen), gelatin offers great utility as the structural component of biomaterials. Taking advantage of reversible guest‐host interactions between β‐cyclodextrin (CD) and adamantane (AD) on modified gelatins, we report the first strategy to afford a self‐healing material based solely on a functionalized extracellular matrix protein. By varying the initial material formulation, hydrogels were synthesized with variable moduli and shear‐thinability across a broad range. Gels were demonstrated to exhibit shear‐thinning and self‐healing properties, supporting protection of clinically relevant stem‐cell‐derived cardiomyocytes during injection. These materials are expected to expand clinical opportunities in cell delivery for in vivo tissue regeneration.

Guest-host supramolecular assembly of injectable hydrogel fibers for cell encapsulation

“…Fibrous hydrogel matrices formed with 5% fiber density (also 2:1 Ad:CD molar ratio) showed improved storage moduli over the 1% fiber density formulation ( Figure S5 ). These results are consistent with previous work demonstrating that the mechanical properties of guest-host materials are dependent on the quantity of guest species compared to host moieties present in the network 42,63 and biopolymer density 42 . Other work with electrospun CD-MeHA fibers assessed the guest-host Ad-CD association strength by “gluing” together two CD-MeHA fiber layers with Ad-functionalized HA (AdHA) 51 .…”

“…Protecting cells during injection and preserving high viability is one of the fundamental requirements for subsequent therapeutic application, but many injectable delivery vehicles suffer from poor cell survival 69,70 . Previous studies have addressed this issue using materials that leverage physical crosslinking since their compliant mechanical properties support non-uniform network deformation 40,63,71 . In these non-uniform matrices, mechanical stresses imposed on the material do not induce uniform strain fields allowing network deformations to dissipate stress 8 .…”

When Cyclodextrins Met Data Science: Unveiling Their Pharmaceutical Applications through Network Science and Text-Mining

“…Photo-responsive βCD supramolecular hydrogels for delivering drugs on demand [ 107 ], injectable αCD hydrogels for plasmid delivery [ 108 ], chitosan–βCD hydrogels for wound dressing [ 109 ], and gelatin–βCD self-healing gels for cell delivery [ 110 ] show how recent research is expanding the scope of fascinating CD-based hydrogel technologies. Hence, CD-based gels are an emerging technology, and a significant increase in research, patents, and innovations in this direction is expected in the years to come.…”

Polymeric Biomaterials for the Treatment of Cardiac Post-Infarction Injuries

“…Cardiac scaffolds based on natural or synthetic biomaterial can mimic the ECM environment, with the further possibility to combine the cell therapy with the release of bioactive molecules [ 21 ]. In this regard, different kinds of systems, either in the form of injectable or implanted scaffolds, have been proposed to date [ 22 , 23 ].…”