Tuning the non-equilibrium state of a drug-encapsulated poly(ethylene glycol) hydrogel for stem and progenitor cell mobilization

Abstract

Injectable and biodegradable hydrogels have been increasingly studied for sustained drug delivery in various molecular therapies. However, it remains a challenge to attain desired delivery rate at injection sites due to local tissue pressures exerted on the soft hydrogels. Furthermore, there is often limited controllability of stiffness and degradation rates, which are key factors required for achieving desired drug release rate and therapeutic efficacy. This study presents a stiff and metastable poly(ethylene glycol) diacrylate (PEGDA)-poly(ethylene imine) (PEI) hydrogel which exhibits an elastic modulus equivalent to bulk plastic materials, and controllable degradation rate independent of its initial elastic modulus. Such unique stiffness was attained from the highly branched architecture of PEI, and the decoupled controllability of degradation rate was achieved by tuning the non-equilibrium swelling of the hydrogel. Furthermore, a single intramuscular administration of granulocyte colony stimulating factor (GCSF)-encapsulated PEGDA-PEI hydrogel extended the mobilization of mononuclear cells to four days. A larger yield of expanded CD34+ and CD31+ endothelial progenitor cells (EPCs) was also obtained as compared to the daily bolus administration. Overall, the hydrogel created in this study will be useful for the controlled and sustained delivery of a wide array of drug molecules.

Blood Outgrowth Endothelial Cells Alter Remodeling of Completely Biological Engineered Grafts Implanted into the Sheep Femoral Artery

“…Given the BOEC growth characteristics we have observed, this delay could be reduced to as little as 3 weeks to achieve the necessary cell number to fully endothelialize a 15-cm graft for utilization in coronary artery bypass. In addition, studies have described the ability to enhance endothelial progenitor mobilization through systemic delivery of cytokines [18, 19], which could substantially diminish this delay even further. Short TEVG (2–3 cm) implanted interpositionally into the ovine femoral artery were used in these studies to evaluate the effects of BOEC seeding on graft remodeling and for comparison to our prior studies implanting unseeded TEVG in this pre-clinical model.…”

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

“…Both secondary and primary amines have been used as nucleophilic groups; [54][55][56] however, this chemistry requires pre-fabrication of the gels at elevated temperatures under basic conditions, limiting their utility as injectable precursors. Instead, the lower p K a (≈8) and stronger nucleophilicity of thiols relative to amines have made thiols the predominant nucleophile used for cross-linking under physiological conditions.…”

Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration

“…Following this fundamental principle, Liang et al . synthesized poly(ethylene glycol) diacrylate (PEGDA)-poly(ethyleneimine) (PEI) hydrogels with controllable degradation rates by varying the presence of protonated amine groups (Figure 3A) [89]. The injectable system delivered the granulocyte colony stimulate factor (GSCF) in a sustained manner both in vitro and in vivo .…”