Biphasic Ferrogels for Triggered Drug and Cell Delivery

Abstract

Ferrogels are an attractive material for many biomedical applications due to their ability to deliver a wide variety of therapeutic drugs on-demand. However, typical ferrogels have yet to be optimized for use in cell-based therapies, as they possess limited ability to harbor and release viable cells. Previously, we have demonstrated an active porous scaffold that exhibits large deformations under moderate magnetic fields, resulting in enhanced biological agent release. However, at small device sizes optimal for implantation (e.g., 2 mm thickness), these monophasic ferrogels no longer achieve significant deformation due to a reduced body force. In this study, we present a new biphasic ferrogel containing an iron oxide gradient capable of large deformations and triggered release even at small gel dimensions. Biphasic ferrogels demonstrate increased porosity, enhanced mechanical properties, and potentially increased biocompatibility due to their reduced iron oxide content. With their ability to deliver drugs and cells on-demand, it is expected that these ferrogels will have wide utility in the fields of tissue engineering and regenerative medicine.

Harnessing magnetic-mechano actuation in regenerative medicine and tissue engineering

“…Soft and hard materials are susceptible to acquiring magnetic properties through the incorporation of magnetic iron oxide particles, as demonstrated in the development of magnetic hydrogels [85], magnetic bioactive glasses [86] magnetic blends of poly(caprolactone) (PCL)/hydroxyapatite [86], magnetic nanofibrous hydroxyapatite poly-lactide acid (PLA) [87],and magnetic PCL [88]. The methods for incorporation of magnetic particles in biomaterials include doping, blending, in situ precipitation, and the 'graftingonto' method [89].…”

“…Although the biophysical and biochemical mechanisms underlying this response remain elusive, it is postulated that magnetisation induces local deformation of the scaffold, which in turns mechanically stimulates cells [61] ( Figure 2C). Magnetically actuated scaffolds also provide a platform for cell and drug delivery on demand [85]. Typically, this is performed with ferromagnetic hydrogels (ferrogels), consisting of hydrogels incorporating ferromagnetic particles and further enriched with growth factors and/or cells ( Figure 2D).…”

Biologic-free mechanically induced muscle regeneration

“…A key event leading to fibrous capsule formation is the adhesion of profibrotic macrophages, foreign body giant cells, and fibroblasts to the implant surface, as these cells secrete proteins that modulate fibrosis and increase collagen deposition (35,36). Previous in vitro experiments have demonstrated significant fibroblast and myoblast cell expulsion from RGD peptide-containing ferrogels in vitro, even with stimulation patterns shorter and less frequent than used here (30,31). It is possible that invading cells near the scaffold edges were expelled from the ferrogel system upon stimulation, because of fluid convection resulting from large gel deformations, leading to an overall diminished cell presence within the scaffold.…”

“…Biphasic ferrogel scaffolds (7 wt% iron oxide) were fabricated with alginate covalently modified with RGD peptide, as previously described (30). Scaffolds were placed s.c. on the tibialis anterior muscle and stimulated for 5 min at 1 Hz every 12 h by approaching and retracting a permanent magnet with a surface field of 6,510 Gauss.…”

“…Previously, it has been demonstrated that magnetically responsive biomaterials termed ferrogels are capable of rapid, on-demand deformations in response to externally applied magnetic fields (30,31). In particular, ferrogels containing an iron oxide gradient (biphasic ferrogels) possess a capacity for large, fatigue-resistant deformations even at device sizes appropriate for small animal implantation.…”