skip to main content

This content will become publicly available on March 30, 2023

Title: 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.
; ; ; ;
Award ID(s):
Publication Date:
Journal Name:
Journal of Materials Chemistry B
Page Range or eLocation-ID:
2194 to 2203
Sponsoring Org:
National Science Foundation
More Like this
  1. 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-termmore »physical dispersion stability. Therefore, the co-hydrogel system is promising for drug delivery applications on mucosal surfaces.« less
  2. 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.
  3. Hydrogels from biopolymers are readily synthesized, can possess various characteristics for different applications, and have been widely used in biomedicine to help with patient treatments and outcomes. Polysaccharides, polypeptides, and nucleic acids can be produced into hydrogels, each for unique purposes depending on their qualities. Examples of polypeptide hydrogels include collagen, gelatin, and elastin, and polysaccharide hydrogels include alginate, cellulose, and glycosaminoglycan. Many different theories have been formulated to research hydrogels, which include Flory-Rehner theory, Rubber Elasticity Theory, and the calculation of porosity and pore size. All these theories take into consideration enthalpy, entropy, and other thermodynamic variables so that the structure and pore sizes of hydrogels can be formulated. Hydrogels can be fabricated in a straightforward process using a homogeneous mixture of different chemicals, depending on the intended purpose of the gel. Different types of hydrogels exist which include pH-sensitive gels, thermogels, electro-sensitive gels, and light-sensitive gels and each has its unique biomedical applications including structural capabilities, regenerative repair, or drug delivery. Major biopolymer-based hydrogels used for cell delivery include encapsulated skeletal muscle cells, osteochondral muscle cells, and stem cells being delivered to desired locations for tissue regeneration. Some examples of hydrogels used for drug and biomolecule delivery includemore »insulin encapsulated hydrogels and hydrogels that encompass cancer drugs for desired controlled release. This review summarizes these newly developed biopolymer-based hydrogel materials that have been mainly made since 2015 and have shown to work and present more avenues for advanced medical applications.« less
  4. Fibrotic disorders account for over one third of mortalities worldwide. Despite great efforts to study the cellular and molecular processes underlying fibrosis, there are currently few effective therapies. Dual-stage polymerization reactions are an innovative tool for recreating heterogeneous increases in extracellular matrix (ECM) modulus, a hallmark of fibrotic diseases in vivo . Here, we present a clickable decellularized ECM (dECM) crosslinker incorporated into a dynamically responsive poly(ethylene glycol)-α-methacrylate (PEGαMA) hybrid-hydrogel to recreate ECM remodeling in vitro . An off-stoichiometry thiol–ene Michael addition between PEGαMA (8-arm, 10 kg mol −1 ) and the clickable dECM resulted in hydrogels with an elastic modulus of E = 3.6 ± 0.24 kPa, approximating healthy lung tissue (1–5 kPa). Next, residual αMA groups were reacted via a photo-initiated homopolymerization to increase modulus values to fibrotic levels ( E = 13.4 ± 0.82 kPa) in situ . Hydrogels with increased elastic moduli, mimicking fibrotic ECM, induced a significant increase in the expression of myofibroblast transgenes. The proportion of primary fibroblasts from dual-reporter mouse lungs expressing collagen 1a1 and alpha-smooth muscle actin increased by approximately 60% when cultured on stiff and dynamically stiffened hybrid-hydrogels compared to soft. Likewise, fibroblasts expressed significantly increased levels of the collagen 1a1more »transgene on stiff regions of spatially patterned hybrid-hydrogels compared to the soft areas. Collectively, these results indicate that hybrid-hydrogels are a new tool that can be implemented to spatiotemporally induce a phenotypic transition in primary murine fibroblasts in vitro .« less
  5. Poly(acrylamide- co -acrylic acid) (P(AAm- co -AA)) hydrogels are highly tunable and pH-responsive materials frequently used in biomedical applications. The swelling behavior and mechanical properties of these gels have been extensively characterized and are thought to be controlled by the protonation state of the acrylic acid (AA) through the regulation of solution pH. However, their tribological properties have been underexplored. Here, we hypothesized that electrostatics and the protonation state of AA would drive the tribological properties of these polyelectrolyte gels. P(AAm- co -AA) hydrogels were prepared with constant acrylamide (AAm) concentration (33 wt%) and varying AA concentration to control the amount of ionizable groups in the gel. The monomer:crosslinker molar ratio (200:1) was kept constant. Hydrogel swelling, stiffness, and friction behavior were studied by systematically varying the acrylic acid (AA) concentration from 0–12 wt% and controlling solution pH (0.35, 7, 13.8) and ionic strength ( I = 0 or 0.25 M). The stiffness and friction coefficient of bulk hydrogels were evaluated using a microtribometer and borosilicate glass probes as countersurfaces. The swelling behavior and elastic modulus of these polyelectrolyte hydrogels were highly sensitive to solution pH and poorly predicted the friction coefficient ( µ ), which decreased with increasing AA concentration. P(AAm- comore »-AA) hydrogels with the greatest AA concentrations (12 wt%) exhibited superlubricity ( µ = 0.005 ± 0.001) when swollen in unbuffered, deionized water (pH = 7, I = 0 M) and 0.5 M NaOH (pH = 13.8, I = 0.25 M) ( µ = 0.005 ± 0.002). Friction coefficients generally decreased with increasing AA and increasing solution pH. We postulate that tunable lubricity in P(AAm- co -AA) gels arises from changes in the protonation state of acrylic acid and electrostatic interactions between the probe and hydrogel surface.« less