Injectable Superparamagnets: Highly Elastic and Degradable Poly(N-isopropylacrylamide)–Superparamagnetic Iron Oxide Nanoparticle (SPION) Composite Hydrogels

Abstract

Injectable, in situ-gelling magnetic composite materials have been fabricated by using aldehyde-functionalized dextran to cross-link superparamagnetic nanoparticles surface-functionalized with hydrazide-functionalized poly(N-isopropylacrylamide) (pNIPAM). The resulting composites exhibit high water contents (82-88 wt.%) while also displaying significantly higher elasticities (G' >60 kPa) than other injectable hydrogels previously reported. The composites hydrolytically degrade via slow hydrolysis of the hydrazone cross-link at physiological temperature and pH into degradation products that show no significant cytotoxicity. Subcutaneous injections indicate only minor chronic inflammation associated with material degradation, with no fibrous capsule formation evident. Drug release experiments indicate the potential of these materials to facilitate pulsatile, "on-demand" changes in drug release upon the application of an external oscillating magnetic field. The injectable but high-strength and externally triggerable nature of these materials, coupled with their biological degradability and inertness, suggest potential biological applications in tissue engineering and drug delivery.

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

“…As such, minimizing the viscosity of the precursor solution would facilitate use of the formulation in the maximum possible alter cell/protein interactions with the hydrogel in tissue engineering applications or induce pulsatile release in drug delivery applications. [ 35,37 ] …”

“…In most cases, this has been achieved by physically separating the two reactive polymer components in separate barrels of a double-barrel syringe, analogous to epoxy glue; co-extrusion of the two polymers through a static mixer mixes the precursor polymers on contact to induce gelation only upon delivery. [35][36][37][38] Alternatively, precursor polymer solutions can be stored pre-mixed at pH conditions not amenable to cross-linking, using the body chemistry to actively titrate the mixture upon injection to physiological pH to drive gelation. In either case, for practical clinical use, the precursor polymer solutions must be stable in the preloaded solutions over the course of several months at room temperature or, at minimum, under refrigerated storage without undergoing signifi cant degradation or deactivation of the reactive functional groups.…”

Novel Nanomaterials Enable Biomimetic Models of the Tumor Microenvironment

“…While the majority of these composite hydrogels for this purpose deliver traditional chemotherapeutics, such as DOX, there have been pushes to incorporate a more novel therapeutic, such as siRNA [51]. Additionally, while typically NIR or other light is typically used to release therapeutic, other methods are available, such as external magnetic eld application [52].…”

Dynamic and biocompatible thermo-responsive magnetic hydrogels that respond to an alternating magnetic field

“…These magnetic hydrogels have a reversible behavior and therefore can re-acquire the initial conformation when the AMF is off [14]. Several groups have thus developed remotely triggered drug delivery systems with micro-gels [15,16], injectable hydrogels [17] and solid patches that can release drug when exposed to an AMF [14,18]. Others have proposed hydrogels that potentially can target and heat a tumor for hyperthermia treatment [19].…”