734 research outputs found
Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering
Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells
Recommended from our members
Multi-Material Stereolithography: Spatially-Controlled Bioactive Poly(Ethylene Glycol) Scaffolds for Tissue Engineering
Challenges remain in tissue engineering to control the spatial and temporal mechanical and
biochemical architectures of scaffolds. Unique capabilities of stereolithography (SL) for
fabricating multi-material spatially-controlled bioactive scaffolds were explored in this work. To
accomplish multi-material builds with implantable materials, a new mini-vat setup was designed,
constructed and placed on top of the existing build platform to allow for accurate and selfaligning X-Y registration during fabrication. Precise quantities of photocrosslinkable solution
were added to and removed from the mini-vat using micro-pipettes. The mini-vat setup allowed
the part to be easily removed and rinsed and different photocrosslinkable solutions could be
easily removed and added to the vat to aid in multi-material fabrication. Two photocrosslinkable
hydrogel biopolymers, poly(ethylene glycol dimethacrylate) (PEG-dma, molecular wt 1,000) and
poly(ethylene glycol)-diacrylate (PEG-da, molecular wt 3,400), were used as the primary
scaffold materials, and controlled concentrations of fluorescently labeled dextran or bioactive
PEG were prescribed and fabricated in different regions of the scaffold using SL. The
equilibrium swelling behavior of the two biopolymers after SL fabrication was determined and
used to design constructs with the specified dimensions at the swollen state. Two methods were
used to measure the spatial gradients enabled by this process with multi-material spatial control
successfully demonstrated down to 500-”m. First, the presence of the fluorescent component in
specific regions of the scaffold was analyzed with fluorescent microscopy. Second, human
dermal fibroblast cells were seeded on top of the fabricated scaffolds with selective bioactivity,
and phase contrast microscopy images were used to show specific localization of cells in the
regions patterned with bioactive PEG. The use of multi-material SL and the relative ease of
conjugating different bioactive ligands or growth factors to PEG allows for the fabrication of
tailored three-dimensional constructs with specified spatially-controlled bioactivity.Mechanical Engineerin
PDMS\u3csub\u3estar\u3c/sub\u3e-PEG Hydrogels Prepared Via Solvent-Induced Phase Separation (SIPS) and Their Potential Utility as Tissue Engineering Scaffolds
Inorganic-organic hydrogels based on methacrylated star polydimethylsiloxane (PDMSstar-MA) and diacrylated poly(ethylene glycol) (PEG-DA) macromers were prepared via solvent-induced phase separation (SIPS). The macromers were combined in a dichloromethane precursor solution and sequentially photopolymerized, dried and hydrated. The chemical and physical properties of the hydrogels were further tailored by varying the number average molecular weight (Mn) of PEG-DA (Mn = 3.4k and 6k g mol-1) as well as the weight percent ratio of PDMSstar-MA (Mn = 7k g mol-1) to PEG-DA from 0:100 to 20:80. Compared to analogous hydrogels fabricated from aqueous precursor solutions, SIPS produced hydrogels with a macroporous morphology, a more even distribution of PDMSstar-MA, increased modulus and enhanced degradation rates. The morphology, swelling ratio, mechanical properties, bioactivity, non-specific protein adhesion, controlled introduction of cell adhesion, and cytocompatibility of the hydrogels were characterized. As a result of their tunable properties, this library of hydrogels is useful to study material-guided cell behavior and ultimate tissue regeneration
Superelastic and pH-Responsive Degradable Dendrimer Cryogels Prepared by Cryo-aza-Michael Addition Reaction
Dendrimers exhibit super atomistic features by virtue of their well-defined discrete quantized nanoscale structures. Here, we show that hyperbranched amine-terminated polyamidoamine (PAMAM) dendrimer G4.0 reacts with linear polyethylene glycol (PEG) diacrylate (575âg/mol) via the aza-Michael addition reaction at a subzero temperature (â20â°C), namely cryo-aza-Michael addition, to form a macroporous superelastic network, i.e., dendrimer cryogel. Dendrimer cryogels exhibit biologically relevant Youngâs modulus, high compression elasticity and super resilience at ambient temperature. Furthermore, the dendrimer cryogels exhibit excellent rebound performance and do not show significant stress relaxation under cyclic deformation over a wide temperature range (â80 to 100â°C). The obtained dendrimer cryogels are stable at acidic pH but degrade quickly at physiological pH through self-triggered degradation. Taken together, dendrimer cryogels represent a new class of scaffolds with properties suitable for biomedical applications
Effects of a synthetic bioactive peptide on neurite growth and nerve growth factor release in chondroitin sulfate hydrogels.
Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. Furthermore, cultures of chick dorsal root ganglia in gels of hyaluronic acid or chondroitin sulfate revealed enhanced growth in chondroitin sulfate gels only upon addition of peptide. Taken together, these results suggest a synergistic nerve growth factor-binding activity between this peptide and chondroitin sulfate
Optofluidic fabrication for 3D-shaped particles.
Complex three-dimensional (3D)-shaped particles could play unique roles in biotechnology, structural mechanics and self-assembly. Current methods of fabricating 3D-shaped particles such as 3D printing, injection moulding or photolithography are limited because of low-resolution, low-throughput or complicated/expensive procedures. Here, we present a novel method called optofluidic fabrication for the generation of complex 3D-shaped polymer particles based on two coupled processes: inertial flow shaping and ultraviolet (UV) light polymerization. Pillars within fluidic platforms are used to deterministically deform photosensitive precursor fluid streams. The channels are then illuminated with patterned UV light to polymerize the photosensitive fluid, creating particles with multi-scale 3D geometries. The fundamental advantages of optofluidic fabrication include high-resolution, multi-scalability, dynamic tunability, simple operation and great potential for bulk fabrication with full automation. Through different combinations of pillar configurations, flow rates and UV light patterns, an infinite set of 3D-shaped particles is available, and a variety are demonstrated
Modeling Small Molecule Elution From a Hydrogel using a Microfluidic Technique
Drug release from a fluid-contacting biomaterial is simulated using a microfluidic device with channels defined by solute-loaded hydrogel. In order to mimic a drug delivery device, a solution of poly(ethylene glycol) diacrylate (PEG-DA), solute, and photoinitiator is cured inside a microfluidic device with a channel through the center ofthe hydrogel. As water is pumped through the channel, solute diffuses out of the hydrogel and into the water. Channel sizes within the devices range from 300 ”m to 1000 ”m to simulate vessels within the body. The properties of the PEG hydrogel were characterizedby the extent of crosslinking, the swelling ratio, and the mesh size of the gel. The structure of the hydrogel was related to the UV exposure dosage and the initial water and solute content in the PEG-DA solution
Macroporous PDMSstarâMA:PEG-DA Hydrogels for Osteochondral Regeneration
Osteochondral defects (OCDs) are the result of severe cartilage loss leading to exposure and damage of the subchondral bone. âMaterials-guidedâ tissue engineering is a promising approach to treat these defects, in which a scaffold may mediate the process of OCD regeneration via instructive and tunable physical and chemical properties. For effective healing, an ideal scaffold would spatially direct tissue to mimic the native transition of the osteochondral interface. Conventional poly(ethylene glycol) diacrylate (PEG-DA) hydrogels prepared using aqueous precursor solutions have been commonly studied for tissue engineering purposes, but lack a wide range of desired chemical and physical properties. This study will seek to develop a superior PEG-DA scaffold for OCD repair by (1) integrating methacrylated star polydimethylsiloxane (PDMSstar-MA) to increase bioactivity and osteoinductivity, (2) employing solvent induced phase separation (SIPS) with the use of an organic solvent, and (3) incorporating salt leaching techniques to achieve an interconnected network of pores to allow for cell infiltration. Total macromer concentration (20, 30, and 40 wt%), ratio of PDMSstar-MA to PEG-DA (0:100 and 20:80 wt%), and average salt particle size will be studied with regard to their impact on scaffold morphology, swelling, mechanical properties, and degradation. The tunable nature of these hydrogels could prove especially useful to study material-guided cell behavior for the purpose of osteochondral tissue regeneration
Enhancing Osteochondral Regeneration Using Human Mesenchymal Stem Cells
An osteochondral defect is a joint injury characterized by the loss of cartilage along with a thin layer of bone beneath it. The cause of this condition is attributed to a number of factors, including repetitive trauma within the joint, metabolic disorders, and genetic predisposition to diseases such as osteoarthritis. Current treatments are partially successful in returning function, but more effective methods are needed for a longer lasting result and better osseointegration of grafts. We hypothesized that a collagen hydrogel synthesized with inorganic Poly(dimethyl siloxane) star-methacrylate (PDMS*-MA) and Poly(ethylene glycol)-diacrylate (PEG-DA) would promote an increased osteogenic phenotype of encapsulated human mesenchymal stem cells (hMSCs). Specifically, this osteogenic hydrogel (CPP* hydrogel) was created as an interpenetrating polymer network composed of a collagen hydrogel soaked with monomers of PEG-DA and PDMS*-MA. The CPP* hydrogel was shown to have superior mechanical properties than typical collagen hydrogels while maintaining an appropriate swelling ratio to support cell culture. Confocal imaging of the CPP* hydrogels revealed that the encapsulated hMSCs were able to survive the hydrogel formulation steps and assume a morphology characteristic of osteoblasts
- âŠ