An official website of the United States government
Abstract Controlled degradation of hydrogels enables several applications of these materials, including controlled drug and cell release applications and directed growth of neural networks. These applications motivate the need of a simulation framework for modeling controlled degradation in hydrogels. We develop a Dissipative Particle Dynamics (DPD) framework for hydrogel degradation. As a model hydrogel, we prepare a network formed by end-linking tetra-arm polyethylene glycol precursors. We model bond breaking during degradation of this hydrogel as a stochastic process. The fraction of degradable bonds follows first order degradation kinetics. We characterize the rate of mass loss during degradation process.
more »
« less
Finding the sweet spot: a library of hydrogels with tunable degradation for tissue model development
In vitro models are valuable tools for applications including understanding cellular mechanisms and drug screening. Hydrogel biomaterials facilitate in vitro models by mimicking the extracellular matrix and in vivo microenvironment. However, it can be challenging for cells to form tissues in hydrogels that do not degrade. In contrast, if hydrogels degrade too much or too quickly, tissue models may be difficult to assess in a high throughput manner. In this paper, we present a poly(allylamine) (PAA) based synthetic hydrogel system which can be tuned to control the mechanical and chemical cues provided by the hydrogel scaffold. PAA is a polycation with several biomedical applications, including the delivery of small molecules, nucleic acids, and proteins. Based on PAA and poly(ethylene glycol) (PEG), we developed a synthetic non-degradable system with potential applications for long-term cultures. We then created a second set of gels that combined PAA with poly- l -lysine (PLL) to generate a library of semi-degradable gels with unique degradation kinetics. In this work, we present the hydrogel systems’ synthesis, characterization, and degradation profiles along with cellular data demonstrating that a subset of gels supports the formation of endothelial cell cord-like structures.
more »
« less
- Award ID(s):
- 1804743
- PAR ID:
- 10350666
- Date Published:
- Journal Name:
- Journal of Materials Chemistry B
- Volume:
- 10
- Issue:
- 13
- ISSN:
- 2050-750X
- Page Range / eLocation ID:
- 2194 to 2203
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Stimuli–responsive biomaterials may be used to better control the release of bioactive molecules or cells for applications involving drug delivery and controlled cell release. In this study, we developed a Factor Xa (FXa)‐responsive biomaterial capable of controlled release of pharmaceutical agents and cells from in vitro culture. FXa‐cleavable substrates were formed as hydrogels that degraded in response to FXa enzyme over several hours. Hydrogels were shown to release both heparin and a model protein in response to FXa. Additionally, RGD‐functionalized FXa‐degradable hydrogels were used to culture mesenchymal stromal cells (MSCs), enabling FXa‐mediated cell dissociation from hydrogels in a manner that preserved multicellular structures. Harvesting MSCs using FXa‐mediated dissociation did not influence their differentiation capacity or indoleamine 2,3‐dioxygenase (IDO) activity (a measure of immunomodulatory capacity). In all, this FXa‐degradable hydrogel is a novel responsive biomaterial system that may be used for on‐demand drug delivery, as well as for improving processes for in vitro culture of therapeutic cells.more » « less
-
The post-polymerization modification of polyglycidol is of great interest for the synthesis of functional polyether-based polymeric biomaterials. We present a degradable polyglycidol-based hydrogel system using oxime click chemistry by employing a ketone-functionalized and an amino-oxy functionalized branched polyglycidol. Ratio-controlled amino-oxy functionalized species were obtained by controlling the ratio of N-hydroxy phthalimide to the hydroxyl groups attached to the polyether backbone. A similar strategy was utilized to obtain ratio-controlled keto functionalized branched polyglycidols. This unique feature will allow for the tailoring of this branched PEG-like structural motif for the synthesis of novel biomaterials with tailored biochemical and biomechanical properties. The bio-orthogonal nature of this crosslinking reaction makes these hydrogels an attractive option for load-bearing tissue engineering. Our hydrogel synthesis methodology allows for control over the properties of the resulting polymeric network, based upon the ratio between the keto and the amino-oxy functionalities. The potential of these polyether-based networks to serve as a successful delivery platform was assessed by studying their swelling and degradation profiles. Biocompatibility and cytotoxicity of the gels were studied using NIH 3T3 cells. Our preliminary results highlighting the potential of our hydrogels platform will be discussed.more » « less
-
A self-assembled co-hydrogel system with sol-gel two-phase coexistence and mucoadhesive properties was developed based on the combined properties of fluoroalkyl double-ended poly(ethylene glycol) (Rf-PEG-Rf) and poly(acrylic acid) (PAA), respectively. We have synthesized an Rf-PEG-g-PAA (where g denotes grafted) copolymer and integrated it into the Rf-PEG-Rf physically cross-linked micellar network to form a co-hydrogel system. Tensile strengths between the co-hydrogel surfaces and two different sets of mucosal surfaces were acquired. One mucosal surface was made of porcine stomach mucin Type II, while the other one is a pig small intestine. The experimental results show that the largest maximum detachment stresses (MDSs) were obtained when the Rf-PEG-g-PAA’s weight percent in the dehydrated polymer mixture is ~15%. Tensile experiments also found that MDSs are greater in acidic conditions (pH = 4–5) (123.3 g/cm2 for the artificial mucus, and 43.0 g/cm2 for pig small intestine) and basic conditions (pH = 10.6) (126.9 g/cm2, and 44.6 g.cm2, respectively) than in neutral pH (45.4 g/cm2, and 30.7 g.cm2, respectively). Results of the rheological analyses using shear strain amplitude sweep and frequency sweep reveal that the Rf-PEG-g-PAA was physically integrated into the Rf-PEG-Rf micellar network, and the co-hydrogels remain physically cross-linked in three-dimensional micellar networks with long-term physical dispersion stability. Therefore, the co-hydrogel system is promising for drug delivery applications on mucosal surfaces.more » « less
-
This paper studies a polymer network in which crosslinks are degradable but polymer chains are not. We show that entanglements markedly enhance the mechanical properties of the polymer network before degradation and slow down degradation. We synthesize polyacrylamide hydrogels with disulfide crosslinks. In a precursor of a low water-to-monomer molar ratio and low crosslinker-to-monomer molar ratio, the monomers are crowded and the resulting polymer chains are long, so that the entanglements greatly outnumber crosslinks. The as-synthesized hydrogels are submerged in pure water to swell to equilibrium. We show that entanglements enhance the swell resistance of the hydrogel, as well as stiffen and toughen the hydrogel. We further show that entanglements slow down degradation when the hydrogel is submerged in an aqueous solution of cysteine. This work demonstrates that entanglements substantially expand the properties space of degradable polymers.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d1tb02436a
