Supramolecular hydrogels cross-linked by preassembled host–guest PEG cross-linkers resist excessive, ultrafast, and non-resting cyclic compression (original) (raw)
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An in situ forming collagen–PEG hydrogel for tissue regeneration
Acta Biomaterialia, 2012
There are limited options for surgeons to repair simple or complex tissue defects due to injury, illness or disease. Consequently, there are few treatments for many serious ailments, including neural-related injuries, myocardial infarction and focal hyaline cartilage defects. Tissue-engineered scaffolds offer great promise for addressing these wide-ranging indications; however, there are many considerations that need to be made when conceptualizing a product. For many applications, an in situ forming scaffold that could completely fill defects with complex geometries, adhere to adjacent tissues and foster cell proliferation would be ideal. Additionally, the scaffold would preferably have tailored mechanical properties similar to native tissues and highly controllable gelation kinetics, and would not require an external trigger, such as ultraviolet light, for gelation. We have developed a unique injectable hydrogel system composed of collagen and multi-armed poly(ethylene glycol) (PEG) that meets all of these criteria. The collagen component enables cellular adhesion and permits enzymatic degradation, while the multiarmed PEG component has amine-reactive chemistry that also binds proteins/tissue and is hydrolytically degradable. We have characterized the mechanical properties, swelling, degradation rates and cytocompatibility of these novel hydrogels. The hydrogels demonstrated tunable mechanics, variable swelling and suitable degradation profiles. Cells adhered and proliferated to near confluence on the hydrogels over 7 days. These data suggest that these collagen and PEG hydrogels exhibit the mechanical, physical and biological properties suitable for use as an injectable tissue scaffold for the treatment of a variety of simple and complex tissue defects.
ACS Biomaterials Science & Engineering, 2021
Synthetic hydrogels formed from poly(ethylene glycol) (PEG) are widely used to study how cells interact with their extracellular matrix. These in vivo-like 3D environments provide a basis for tissue engineering and cell therapies but also for research into fundamental biological questions and disease modeling. The physical properties of PEG hydrogels can be modulated to provide mechanical cues to encapsulated cells; however, the impact of changing hydrogel stiffness on the diffusivity of solutes to and from encapsulated cells has received only limited attention. This is particularly true in selectively cross-linked "tetra-PEG" hydrogels, whose design limits network inhomogeneities. Here, we used a combination of theoretical calculations, predictive modeling, and experimental measurements of hydrogel swelling, rheological behavior, and diffusion kinetics to characterize tetra-PEG hydrogels' permissiveness to the diffusion of molecules of biologically relevant size as we changed polymer concentration, and thus hydrogel mechanical strength. Our models predict that hydrogel mesh size has little effect on the diffusivity of model molecules and instead predicts that diffusion rates are more highly dependent on solute size. Indeed, our model predicts that changes in hydrogel mesh size only begin to have a non-negligible impact on the concentration of a solute that diffuses out of hydrogels for the smallest mesh sizes and largest diffusing solutes. Experimental measurements characterizing the diffusion of fluorescein isothiocyanate (FITC)-labeled dextran molecules of known size aligned well with modeling predictions and suggest that doubling the polymer concentration from 2.5% (w/v) to 5% produces stiffer gels with faster gelling kinetics without affecting the diffusivity of solutes of biologically relevant size but that 10% hydrogels can slow their diffusion. Our findings provide confidence that the stiffness of tetra-PEG hydrogels can be modulated over a physiological range without significantly impacting the transport rates of solutes to and from encapsulated cells.
PLGA/PEG-hydrogel composite scaffolds with controllable mechanical properties
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2013
Biodegradable polymer scaffolds have great potential for regenerative medicine applications such as the repair of musculoskeletal tissues. Here, we describe the development of scaffolds that blend hydrogel components with thermoplastic materials, combining the unique properties of both components to create mouldable formulations. This study focuses on the structural and mechanical properties of the composite scaffolds, produced by combining temperature-sensitive poly(DL-lactic acid-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) particles with a hydrogel component [Pluronic F127, fibrin or hyaluronic acid (HyA)]. The composite formulations solidified over time at 37 C, with a significant increase (p 0.05) in compressive strength observed from 15 min to 2 h at this temperature. The maximum compressive strength was 1.2 MPa for PLGA/PEG-Pluronic F127 scaffolds, 2.4 MPa for PLGA/ PEG-HyA scaffolds and 0.6 MPa for PLGA/PEG-fibrin scaffolds. Porosity for each of the PLGA/PEG-hydrogel formulations tested was between 50 and 51%. This study illustrates the ability to combine this thermoplastic PLGA/PEG system with hydrogels to fabricate composite scaffolds, and demonstrates that altering the particle to hydrogel ratio produces scaffolds with varying mechanical properties. V
Mechanical Properties of Cellularly Responsive Hydrogels and Their Experimental Determination
Advanced Materials, 2010
responsive hydrogel systems, adhesive ligands and proteolytic degradation sites are readily incorporated by copolymerization of the crosslinking macromers with acrylate functionalized peptides, permitting cells to interact with and/or remodel their microenvironments. However, the nature of the chain polymerization and its associated formation of a carbon-carbon backbone polymer necessitates that cleavable groups for gel degradation must be introduced within the crosslinks. The classically observed polydispersity in the kinetic chain length and crosslinking density is both an advantage (e.g., rapid and robust gel formation) and disadvantage (e.g., non-uniform degradation products and heterogeneous nanoscale structure) of this type of gel system.
Reinforcement of Mono- and Bi-layer Poly(Ethylene Glycol) Hydrogels with a Fibrous Collagen Scaffold
Annals of Biomedical Engineering, 2015
Biomaterial-based tissue engineering strategies hold great promise for osteochondral tissue repair. Yet significant challenges remain in joining highly dissimilar materials to achieve a biomimetic, mechanically robust design for repairing interfaces between soft tissue and bone. This study sought to improve interfacial properties and function in a bilayer, multi-phase hydrogel interpenetrated with a fibrous collagen scaffold. 'Soft' 10% (w/w) and 'stiff' 30% (w/w) PEGDM was formed into mono-or bilayer hydrogels possessing a sharp diffusional interface. Hydrogels were evaluated as single-(hydrogel only) or multi-phase (hydrogel+fibrous scaffold penetrating throughout the stiff layer and extending >500μm into the soft layer). Including a fibrous scaffold into both soft and stiff single-phase hydrogels significantly increased tangent modulus and toughness and decreased lateral expansion under compressive loading. In multi-phase hydrogels, finite element simulations predict substantially reduced stress and strain gradients across the soft-stiff hydrogel interface. When combining two low moduli constituent material, composites theory poorly predicts the observed, large modulus increases. These results suggest material structure associated with the fibrous scaffold penetrating within the PEG hydrogel as the major contributor to improved properties and function-the hydrogel bore compressive loads and the 3D fibrous scaffold was loaded in tension thus resisting lateral expansion.
Biotechnology and …, 2004
A major challenge when designing cell scaffolds for chondrocyte delivery in vivo is creating scaffolds with sufficient mechanical properties to restore initial function while simultaneously controlling temporal changes in the gel structure to facilitate tissue formation. To address this design challenge, degradable photocrosslinked hydrogels based on poly(ethylene glycol) were investigated. To alter the gel's initial mechanical properties, hydrogels were fabricated by varying the initial macromer concentration from 10% to 15% to 20%. A twofold increase in macromer concentration resulted in an eightfold increase in the initial compressive modulus from 60 to 500 kPa. Gel degradation was tailored by incorporating fast-degrading crosslinks that enable maximal extracellular matrix (ECM) diffusion with time and a minimal number of nondegrading (or slowly degrading) crosslinks to maintain scaffold integrity and prevent complete gel erosion during tissue formation. Chondrocytes encapsulated in these gels produced cartilaginous tissue rich in glycosaminoglycans and collagen as seen biochemically and histologically. Interestingly, mass loss appeared to more closely match tissue secretion in gels fabricated from a 15% macromer concentration. However, the spatial ECM distribution was grossly similar in all three gels. By tailoring gel degradation and controlling network evolution during degradation, gels with optimal properties can be fabricated to support initially physiologic compressive loads while simultaneously supporting the formation of a neotissue. B
2010
A new method for encapsulating cells in interpenetrating network (IPN) hydrogels of superior mechanical integrity was developed. In this study, two biocompatible materials-agarose and poly(ethylene glycol) (PEG) diacrylate-were combined to create a new IPN hydrogel with greatly enhanced mechanical performance. Unconfined compression of hydrogel samples revealed that the IPN displayed a fourfold increase in shear modulus relative to a pure PEG-diacrylate network (39.9 vs. 9.9 kPa) and a 4.9-fold increase relative to a pure agarose network (8.2 kPa). PEG and IPN compressive failure strains were found to be 71% AE 17% and 74% AE 17%, respectively, while pure agarose gels failed around 15% strain. Similar mechanical property improvements were seen when IPNs-encapsulated chondrocytes, and LIVE/DEAD cell viability assays demonstrated that cells survived the IPN encapsulation process. The majority of IPN-encapsulated chondrocytes remained viable 1 week postencapsulation, and chondrocytes exhibited glycosaminoglycan synthesis comparable to that of agarose-encapsulated chondrocytes at 3 weeks postencapsulation. The introduction of a new method for encapsulating cells in a hydrogel with enhanced mechanical performance is a promising step toward cartilage defect repair. This method can be applied to fabricate a broad variety of cell-based IPNs by varying monomers and polymers in type and concentration and by adding functional groups such as degradable sequences or cell adhesion groups. Further, this technology may be applicable in other cell-based applications where mechanical integrity of cell-containing hydrogels is of great importance.
Journal of the Mechanical Behavior of Biomedical Materials, 2011
Hydrogels PEGDMA Mechanical properties A B S T R A C T Poly(ethylene glycol) hydrogels are currently under investigation as possible scaffold materials for bone regeneration. The main purpose of this research was to analyse the mechanical properties and thermal behaviour of novel photopolymerised poly(ethylene glycol) dimethacrylate (PEGDMA) based hydrogels. The effect of varying macromolecular monomer concentration, molecular weight and water content on the properties of the resultant hydrogel was apparent. For example, rheological findings showed that storage modulus (G ′ ) of the hydrogels could be tailored to a range between approximately 14,000 and 70,000 Pa by manipulating both of the aforementioned criteria. Equally striking variations in mechanical performance were observed using uniaxial tensile testing where reduction in PEGDMA content in the hydrogels resulted in decrease in both tensile strength and Young's modulus values. Conversely, increases in the elongation at break values were observed as would be expected. Differential scanning calorimetry and dynamic mechanical thermal analysis showed that there was an increase in Tg with an increase in the molecular weight of PEGDMA. The relationship between the initial feed ratio, molecular weight of the macromolecular monomer and the subsequent mechanical properties of the hydrogels are further elucidated throughout this study. 90 6424493. search has received extensive investigation in the literature and is of particular interest for bone regeneration applications. Bone has the ability to repair itself, however the rate and amount of repair are dependent on the actual size of the defect (Muschler and Lane, 1992). Defects of a size that 1751-6161/$ -see front matter c ⃝
Macromolecular Bioscience, 2013
Poly(ethylene glycol) (PEG) hydrogels formed by thiol-norbornene photo-click reaction have been used in a variety of biomedical applications. The mild and rapid thiol-norbornene reaction permits the generation of versatile biomimetic extracellular matrices for studying cell behaviors in 3D. Thiol-norbornene PEG-based hydrogels can be rendered biodegradable if appropriate macromers and cross-linkers are employed. Previous studies have elucidated, experimentally and mathematically, in vitro degradation behaviors of these hydrogels. However, the highly tunable thiol-ene gel degradability and the influence of different forms of gel degradation on promoting cell survival and morphogenesis in 3D have not been fully evaluated. Toward this end, two norbornene-functionalized PEG macromers, namely PEG-tetra-ester-norbornene (PEG4eNB) and PEG-tetra-amide-norbornene (PEG4aNB), were synthesized to render the resulting hydrogels with different hydrolytic degradability. Di-thiol containing likers, such as dithiothreitol or bis-cysteine containing peptides, were utilized to control proteolytic degradability of the gels. The influence of thiol-ene gel degradability on cell survival and morphogenesis in 3D was assessed using human mesenchymal stem cells (hMSCs) and pancreatic MIN6-cells. The results showed that initial cell viability could be negatively affected in highly cross-linked thiol-norbornene hydrogels. In addition, when cells were encapsulated in thiol-ene gels lacking cell-adhesive motifs, their survival and proliferation were promoted in more hydrolytically labile hydrogels. Finally, the degree of 3D cell spreading in encapsulated hMSCs was enhanced when the matrices were immobilized with cell-adhesive motifs and were allowed to degrade both proteolytically and hydrolytically.