Thermally Cross-Linked Oligo(poly(ethylene glycol) fumarate) Hydrogels Support Osteogenic Differentiation of Encapsulated Marrow Stromal Cells In Vitro

Abstract

A novel polymer, oligo(poly(ethylene glycol) fumarate) (OPF), cross-linked with a thermal radical initiation system has recently been developed in our laboratory as an injectable, biodegradable cell carrier for regeneration of orthopaedic tissues. The cross-linking, swelling, and degradative properties of hydrogels prepared from OPF with poly(ethylene glycol) of two different chain lengths were assessed. The two OPF types had similar gelation onset times ( approximately 3.6 min) but, when cross-linked for 8 min at 37 degrees C, exhibited significantly different swelling characteristics (fold swelling: 17.5 +/- 0.2 vs 13.4 +/- 0.4). Rat marrow stromal cells (MSCs) were then directly combined with the hydrogel precursors and encapsulated in a model OPF formulation at approximately 14 million cells/mL, cultured in vitro in the presence of osteogenic supplements (dexamethasone), and monitored over 28 days via histology. MSC differentiation in these samples (6 mm diameter x 0.5 mm thick before swelling), as determined by Von Kossa staining for calcified matrix, was apparent by day 21. At day 28, mineralized matrix could be seen throughout the samples, many microns away from the cells. These experiments strongly support the usefulness of thermally cross-linked OPF hydrogels as injectable cell carriers for bone regeneration.

Subcutaneous tissue response and osteogenic performance of calcium phosphate nanoparticle-enriched hydrogels in the tibial medullary cavity of guinea pigs

“…For injectable hydrogel formulations, OPF and PEGDA were sterilized prior to use via exposure to ultraviolet light for 3 hours and freeze-dried overnight following an established technique [19]. The two components were then transferred in a 2.5 ml syringe under sterile conditions.…”

Oligo[poly(ethylene glycol)fumarate] Hydrogel Enhances Osteochondral Repair in Porcine Femoral Condyle Defects

“…OPF hydrogel is a polymer created through the synthesis of fumaric acid and PEG through ester bonds [26]. The ability of the ester bonds to undergo hydrolysis under acidic and basic conditions confers biodegradable characteristics, of which in vitro [19,21,26,42,54,55,58] and in vivo [13,17,18,57] degradation rates have been reported. It is also biocompatible, evident from in vitro [12, 42-44, 50, 55, 56, 58] and in vivo [13,17,18,57] assessments.…”

“…It possesses a higher water content than other hydrogels, such as poly(glycolic acid) and poly(L-lactic acid) polymer meshes. In addition, it is more biodegradable [19,21,26,42,54,55,58] and biocompatible [13,17,18,57] compared to natural scaffold materials, such as gelatin, collagen, and hyaluronic acid [20]. In a preclinical evaluation of this scaffold, we investigated the effects of freeze-dried OPF hydrogel scaffold in a porcine model, which is more clinically relevant due to greater physiologic and anatomic similarities to humans.…”

Plasma Modification of 3D Hydrogels for Cell Culture Applications

“…Oxidized gels are important and were synthesized to accelerate the degradation rate of several gels [24][25][26][27][28][29][30][31][32]. This approach offers control over the degradation rate by varying the oxidation degree, as increasing the oxidation degree can increase the vulnerability of hydrogels to hydrolysis [26] and [28].…”