Journal: Advanced Science

Article Title: Influence of Microgel and Interstitial Matrix Compositions on Granular Hydrogel Composite Properties

doi: 10.1002/advs.202206117

Figure Lengend Snippet: Fabricating granular hydrogel composites. a) Chemical structure of hyaluronic acid (HA) modified with norbornenes (NorHA) and schematic overview of the covalent crosslinking of NorHA with dithiothreitol (DTT) in the presence of Irgacure 2959 (I2959) photoinitiator and exposure to ultraviolet (UV) light. b) Schematic overview of granular hydrogel composite fabrication from fragmented microgels (inset: fluorescent images of fragmented NorHA microgels) and a photocrosslinkable interstitial matrix and variables investigated in the formulations related to the microgels (i.e., modulus, degradability), interstitial matrix (i.e., modulus, crosslinker chemistry), or the ratio of microgels to interstitial matrix. c) Representative 3D IMARIS reconstructions of confocal z ‐stacks (left: interstitial region, silver; right: microgels, gold) of a granular hydrogel composite consisting of soft NorHA microgels (10 kPa) with 10% NorHA interstitial solution (120 kPa) added (insets: representative 2D slices).

Article Snippet: Both the interstitial matrix and microgel phases could be visualized using fluorescent confocal microscopy, and a 3D reconstruction of the granular hydrogel composite structure was obtained using IMARIS (Figure ; Video , Supporting Information).

Techniques: Modification

Journal: Advanced Science

Article Title: Influence of Microgel and Interstitial Matrix Compositions on Granular Hydrogel Composite Properties

doi: 10.1002/advs.202206117

Figure Lengend Snippet: Influence of microgel modulus on granular hydrogel composite properties. Interstitial matrix is kept constant at 10% added by volume, with a modulus of 120 kPa. a) Schematic overview of granular hydrogel composites with varied microgel moduli. b) Bulk compressive moduli ( n = 8) of hydrogels used to fabricate soft, medium, and stiff microgels (left), and representative images of fluorescently‐labeled microgels in suspension (right). c) Rheological characterization of granular hydrogel composite precursors prior to crosslinking of interstitial matrix, including representative strain sweeps (left, 1–250%), quantification of storage moduli (center, G ′, Pa), and yield strain (right, %), n = 4. d) Compression testing of granular hydrogel composites ( n = 5), including compressive moduli (left), failure strain (center), and failure stress (right). e) Visualization of granular hydrogel composites under compressive loading, including representative images of granular hydrogel composites containing fluorescently labelled soft microgels (1%) initially and immediately before failure during compressive loading (left), and quantified compression of individual microgels at failure (center, n = 14) and total compression of sample at failure (right, n = 3). Statistical analysis performed using a one‐way ANOVA. ns = no significance, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: Both the interstitial matrix and microgel phases could be visualized using fluorescent confocal microscopy, and a 3D reconstruction of the granular hydrogel composite structure was obtained using IMARIS (Figure ; Video , Supporting Information).

Techniques: Labeling, Suspension

Journal: Advanced Science

Article Title: Influence of Microgel and Interstitial Matrix Compositions on Granular Hydrogel Composite Properties

doi: 10.1002/advs.202206117

Figure Lengend Snippet: Influence of interstitial matrix modulus on granular hydrogel composite properties. a) Schematic overview of granular hydrogel composites with varied interstitial matrix moduli. b) Bulk compressive moduli ( n = 8) of hydrogels used to fabricate interstitial matrices. c) Compression testing of granular hydrogel composites ( n = 5), including compressive modulus (left), failure strain (center), and failure stress (right). “None” indicates inter‐particle photocrosslinking with no interstitial matrix present. Interstitial matrix kept consistent at 20% added by volume, and soft microgels used across composites. d) Schematic overview of atomic force microscopy (AFM) testing of the surface of granular hydrogel composites in a (500 µm) 2 area (left), representative elastic moduli (kPa) heat maps (moduli measured every 50 µm in a (500 µm) 2 area) for two granular hydrogel composite formulations where the interstitial matrix varied from 10 to 120 kPa (center), and quantified elastic moduli measurements ( n = 100) across individual samples for the two granular hydrogel composite formulations. Interstitial matrix kept consistent at 10% added by volume, and soft microgels were used across composites. Statistical analysis performed using a one‐way ANOVA. ns = no significance, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: Both the interstitial matrix and microgel phases could be visualized using fluorescent confocal microscopy, and a 3D reconstruction of the granular hydrogel composite structure was obtained using IMARIS (Figure ; Video , Supporting Information).

Techniques: Microscopy

Journal: Advanced Science

Article Title: Influence of Microgel and Interstitial Matrix Compositions on Granular Hydrogel Composite Properties

doi: 10.1002/advs.202206117

Figure Lengend Snippet: Influence of interstitial matrix/microgel ratio on granular hydrogel composite properties. Interstitial matrix (120 kPa) and microgel (soft) moduli kept consistent across granular hydrogel composites. a) Schematic overview of granular hydrogel composites with varied interstitial matrix volume fractions. b) Representative confocal image slices of granular hydrogel composites showing microgels (black) and pores (white) (left), and quantified interstitial space (%) as a function of interstitial solution added (vol %) (right, n = 3). Scale bar = 200 µm. c) Rheological characterization of granular hydrogel composite precursors prior to crosslinking of interstitial matrix, including representative strain sweeps (left, 1–250%), quantification of storage moduli (center, G ′, Pa), and yield strain (right, %), n ≥ 3. d) Compression testing of granular hydrogel composites (with interstitial matrix crosslinked), including compressive modulus (left), failure strain (center), and failure stress (right), n ≥ 4. Statistical analysis performed using a one‐way ANOVA. ns = no significance, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: Both the interstitial matrix and microgel phases could be visualized using fluorescent confocal microscopy, and a 3D reconstruction of the granular hydrogel composite structure was obtained using IMARIS (Figure ; Video , Supporting Information).

Techniques:

Journal: Advanced Science

Article Title: Influence of Microgel and Interstitial Matrix Compositions on Granular Hydrogel Composite Properties

doi: 10.1002/advs.202206117

Figure Lengend Snippet: Extrusion printing with granular hydrogel composites. Interstitial matrix modulus (120 kPa) kept consistent across granular hydrogel composites. Left: Representative images (side and top views) of extrusion printed hollow cylinders (1 cm tall, 1 cm diameter) made from granular hydrogel composite precursor immediately after deposition for various microgel moduli (soft, medium, stiff) and interstitial solution volume percent (0–30%). Right: Quantification of height maintenance for granular hydrogel composite printed structures. An “x” indicates that the structure fully collapsed. Statistical analysis performed using a one‐way ANOVA. n ≥ 3, ns = no significance.

Article Snippet: Both the interstitial matrix and microgel phases could be visualized using fluorescent confocal microscopy, and a 3D reconstruction of the granular hydrogel composite structure was obtained using IMARIS (Figure ; Video , Supporting Information).

Techniques:

Journal: Advanced Science

Article Title: Influence of Microgel and Interstitial Matrix Compositions on Granular Hydrogel Composite Properties

doi: 10.1002/advs.202206117

Figure Lengend Snippet: Influence of interstitial matrix crosslinker chemistry on granular hydrogel composite properties. Microgel modulus (soft, 10 kPa), total concentration of norbornene groups (28 × 10 −3 m ) in interstitial matrix, and amount of consumed norbornene groups (86%) in interstitial matrix kept consistent across granular hydrogel composites. a) Schematic depicting the chemical structure of adamantane‐modified HA (AdHA), and combination with NorHA, thiolated β ‐cyclodextrin (CD‐thiol), I2959, and UV light to form a photocrosslinkable guest–host hydrogel with reversible guest (Ad) and host (CD) bonds (left). Schematic of granular hydrogel composites with either covalent or guest–host crosslinkers within the interstitial matrices (right). b) Quantified compressive moduli (left), failure strain (center), and failure stress (right) of granular hydrogel composites with either covalent or guest–host crosslinkers within the interstitial matrices ( n = 5). c) Representative confocal image slices of granular hydrogel composites with either covalent or guest–host crosslinkers within the interstitial matrices showing microgels (black) and pores (green) (left) and quantified interstitial space (%) as a function of crosslinkers within interstitial matrices (right, n = 3). Scale bar = 200 µm. Statistical analysis performed using a one‐way ANOVA. ** p < 0.01, *** p < 0.001.

Article Snippet: Both the interstitial matrix and microgel phases could be visualized using fluorescent confocal microscopy, and a 3D reconstruction of the granular hydrogel composite structure was obtained using IMARIS (Figure ; Video , Supporting Information).

Techniques: Concentration Assay, Modification

Journal: Advanced Science

Article Title: Influence of Microgel and Interstitial Matrix Compositions on Granular Hydrogel Composite Properties

doi: 10.1002/advs.202206117

Figure Lengend Snippet: Influence of microgel degradability on granular hydrogel composite properties. Interstitial matrix modulus (120 kPa), total concentration of norbornene groups (8 × 10 −3 m ) in microgels, and total consumption of norbornene groups (50%) in microgels kept consistent across granular hydrogel composites. a) Chemical structure of HA modified with norbornene via carbic anhydride (NorHA CA ), and combination with dithiothreitol (DTT), Irgacure 2959 (I2959), and UV light to form a photocrosslinkable, degradable network (left). Schematic of granular hydrogel composites with either nondegradable or degradable microgels (right). b) Macroscopic images (scale bar = 1 cm) of nondegradable and degradable granular hydrogel composites with representative confocal slices (scale bar = 100 µm) depicting granular hydrogel composite structures after 7 days (microgels: pink, interstitial space: green) (left), and quantified interstitial space (%) as a function of microgel degradability at Day 0 and Day 7 (right, n = 3). c) Quantified compressive moduli (left), failure strain (center), and failure stress (right) of degradable (blue) and nondegradable (grey) granular hydrogel composites over 7 days ( n = 4). Statistical analysis performed using a one‐way ANOVA. ns = no significance, * p < 0.05, *** p < 0.001, **** p < 0.0001.

Article Snippet: Both the interstitial matrix and microgel phases could be visualized using fluorescent confocal microscopy, and a 3D reconstruction of the granular hydrogel composite structure was obtained using IMARIS (Figure ; Video , Supporting Information).

Techniques: Concentration Assay, Modification