Chapter Four · failure evidence
What Hydrogel Biomaterial Synthesis got wrong, from 80 dissertations
Synthesized hydrogel biomaterials frequently suffer from physical, chemical, and biological deficiencies during fabrication and biological deployment. Across multiple investigations, networks failed due to mechanical weakness, rapid dissolution, dispensing blockages, cytotoxic reactions, cellular restriction from matrix stiffness, poor degradability, and adhesive detachment. These records come from PhD theses at 25 institutions, 2021 to 2026. Each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.
Hydrogels suffer mechanical failure and low modulus due to insufficient crosslinking density or brittle network structures
Materials formulated with low precursor concentrations, short chain crosslinkers, or non-dissipative networks experienced tearing at clamping interfaces, excessive brittleness, and low compressive or tensile moduli. These formulations failed to retain their shape under load, tore during mechanical handling, or exhibited premature structural fracture compared to baseline materials.
Lost to a baseline
P2Th3Ozi hydrogel achieved lower elongation at failure (121%) compared to PU/PEDOT:PSS composites (200-300%)
Design of printable electroactive biomaterials for tissue engineering · Imperial
Lost to a baseline
Detached hydrogel tensile modulus (MH: 3.76 kPa, PH: 0.78 kPa) was significantly lower than prior compressive testing of 2% OPC chitosan-gelatin hydrogel (127.4 kPa).
Development and evaluation of sustainable hydrogel technologies for tissue engineering · University of Nottingham Repository
Lost to a baseline
CaCO3-crystallized PDE(500) hydrogels had lower storage modulus and higher brittleness than the intermediate Ca2+-doped hydrogels
Lost to a baseline
A10+B10/P8k-0/10 hydrogel had a compressive strength of only 0.16 MPa, which was lower than the 0.24 MPa of the initial A10+B10/P8k-10/0 baseline
Tough Injectable Hydrogels by Combining Elastic and Energy Dissipation · Research Repository UCD
Lost to a baseline
BoneAGE and PLAGE hydrogels with addition of multi-arm PEG thiols (ETTMP) yielded lower storage moduli and slower curing compared to difunctional DTT.
Bio-interactive hydrogels for regenerative medicine Bio-interaktive Hydrogele für die regenerative Medizin · DSpace-CRIS at TU Wien
Lost to a baseline
PEDOT:PSS hydrogels treated with DMSO achieved 2-10 MPa Young's modulus, almost 3-fold lower/softer than water-treated P2Th3Ozi (26.3 MPa)
Design of printable electroactive biomaterials for tissue engineering · Imperial
Lost to a baseline
0.2% MWCNT-ECM hydrogels exhibited lower storage moduli (G') across all ECM concentrations compared to ECM-only control hydrogels.
Combining extracellular matrix hydrogels and electrical stimulation to influence macrophage polarisation · University of Nottingham Repository
Considered and rejected
Considered and rejected: Rejected 5% and 10% w/v HA-SH concentrations for hydrogel synthesis due to poor mechanical integrity and weak network formation.
Hydrogels as Delivery Platforms for Immunotherapeutic Agents in Cancer Therapy · IRIS - UNICAM - prod
Considered and rejected
Considered and rejected: Rejected pure PCL and pure hydrogels for load-bearing bone repair due to poor cell bioactivity and insufficient mechanical strength (<1 MPa), respectively
3D Printed Polycaprolactone/Nano-Hydroxyapatite Scaffolds for Bone Tissue Engineering In-Vitro · HARVEST
Considered and rejected
Considered and rejected: Rejected agarose hydrogel for ultra-soft (<20 kPa) channel fabrication because it fails to retain structural shape and degrades optical transparency.
Ultrasound-driven microbubble dynamics in microvessels · Imperial
Considered and rejected
Considered and rejected: Bulk hydrogel scaffolds were rejected because they lacked the structural and mechanical integrity required for handling, suturing, and clamping into the bioreactor.
MIMICKING THE BIOPHYSICAL NICHE OF NATIVE SKELETAL MUSCLE FOR THE FORMATION OF A 3D, TISSUE-ENGINEERED SKELETAL MUSCLE CONSTRUCT · JScholarship
Considered and rejected
Considered and rejected: Rejected 2.5% PEG-4MAL hydrogels despite least swelling because they exhibited weakest mechanical properties
T cell Immunomodulation in the Lymph Node for Inhibition of Load-Induced Osteoarthritis · Cornell
Tried and failed
hydrogel with low crosslinker ratio applied to microneedle skin insertion. Outcome: unstable. Reason: insufficient crosslinking led to poor mechanical strength causing mechanical failure during insertion
Engineered Microneedle Patches for Biomarker Quantification and Interstitial Fluid Collection · Georgia Tech
Tried and failed
photopolymerization with low precursor or initiator concentration applied to hydrogel fabrication. Reason: insufficient crosslinking led to hydrogels that were too mechanically weak to handle
POLYMERIZATION AND VOLUMETRIC PRINTING OF SOFT COMPOSITES · Cornell
Tried and failed
low molecular weight photopolymerizable macromer hydrogel applied to in situ endovascular embolization. Reason: short crosslinker chain length led to excessive brittleness and premature mechanical failure under compression
In situ photopolymerizable hydrogels for intracranial aneurysms treatment · EPFL
Tried and failed
photocrosslinking large hydrogel volumes with low initiator concentration applied to low degree of functionalization GelMA hydrogels. Reason: slow crosslinking kinetics led to inadequate network formation and poor mechanical integrity
Lost to a baseline
A10+B20/P4k-0/10 hydrogel had a compressive toughness of 11.28 kJ/m³, which was lower than the 12.05 kJ/m³ of the A10+B20/P4k-1/9 formulation.
Tough Injectable Hydrogels by Combining Elastic and Energy Dissipation · Research Repository UCD
Considered and rejected
Considered and rejected: Rejected pure GEL-NB formulations because they failed to form freestanding structural hydrogels suitable as electrode coatings.
An engineered biosynthetic hydrogel for 3D neural tissue interfaces · Imperial
Tried and failed
mechanical clamping for tensile testing applied to gelatin hydrogels. Reason: hydrogels tore and disintegrated at grip and pin attachment points across all tested concentrations
Mechanical tension in pancreatic ductal adenocarcinoma progression · Imperial
Lost to a baseline
Silk granular hydrogels exhibited substantially lower tensile strain at failure (29–62%) compared to neat PEGDM and composites (>90%)
Lost to a baseline
A single-layer tough hydrogel shell fractured under 25.8% strain and 0.108 N force, necessitating triple-layer coating to avoid compression failure.
Lost to a baseline
Double network hydrogel (DN) compressive modulus dropped to 25 kPa in the swollen state, losing to neat PEGDM hydrogel at ~35 kPa
Lost to a baseline
Dynamic covalent hydrogels exhibited lower plateau modulus (7.5 kPa for PEG-CBCA, 2.1 kPa for PEG-BCA) compared to irreversible thiol-acrylate Michael addition hydrogels (~10.5 kPa) at 10 wt%.
Investigating the stimuli responsiveness of reversible thia-conjugate addition crosslinked hydrogels · UT Austin
Considered and rejected
Considered and rejected: Decided against using pure gelatin hydrogels as stretch substrates due to repeated mechanical failure at actuator clamping interfaces.
Mechanical tension in pancreatic ductal adenocarcinoma progression · Imperial
Considered and rejected
Considered and rejected: Rejected single-network PEGDMA and non-dissipative adhesive hydrogels because cracks propagate catastrophically immediately after initiation due to brittle interface behavior.
Considered and rejected
Considered and rejected: Directly incorporating synthetic short-chain networks into standard hydrogels was rejected for dynamic tissues due to fatigue failure from permanent sacrificial bond rupture.
Hydrogels undergo rapid hydrolytic degradation, dissolution, and swelling instability in aqueous conditions
Formulations containing unstable ester linkages, low polymer modification, or insufficient physical annealing suffered from rapid matrix breakdown and excessive osmotic swelling. These networks disintegrated prematurely during saline washing, prolonged water immersion, or extended cell culture, causing matrix warping and payload loss.
Tried and failed
incorporating hydrolytically degradable ester monomers into hydrogels applied to hydrogel scaffolds for cell culture. Outcome: unstable. Reason: rapid degradation destabilised the matrix structure causing abnormal cell clustering and altered morphology
DESIGNING HYALURONIC ACID GRANULAR HYDROGELS FOR BIOMATERIALS APPLICATIONS · Penn
Tried and failed
low-concentration thiol-ene photocrosslinked hybrid hydrogels applied to in vitro cell culture scaffolds. Outcome: unstable. Reason: insufficient network crosslinking density led to premature hydrolytic or enzymatic degradation within days
An engineered biosynthetic hydrogel for 3D neural tissue interfaces · Imperial
Tried and failed
low-concentration collagen hydrogel microwell fabrication applied to extended embryo culture. Outcome: unstable. Reason: hydrogel degraded and warped significantly over the prolonged culture period
Tried and failed
hydrogel encapsulation for bacterial immobilization applied to wastewater bioreactors. Outcome: unstable. Reason: matrix degraded, suffered osmotic swelling, and lost structural integrity during wastewater incubation
Tried and failed
Ester-linked synthetic polymer hydrogel crosslinking applied to in vivo cell delivery scaffolds. Outcome: unstable. Reason: In vivo enzymatic or physiological conditions accelerated hydrolytic degradation far faster than in vitro predictions
Synthetic Hydrogels for the Maturation and Engraftment of Stem Cell-Derived Beta Cells · Georgia Tech
Lost to a baseline
Matrigel lost mechanical integrity and softened prematurely after 6 days of hepatic organoid culture compared to stably crosslinked PEG-RGD hydrogels which supported growth for over 14 days.
Defined matrices for epithelial organoid culture and disease modelling · EPFL
Considered and rejected
Considered and rejected: Hydrogels with low degree of modification (~5%) were rejected due to weaker mechanical properties and higher rates of degradation that compromised temporal stability.
Biomaterial-driven lymphangiogenesis using click-crosslinked gelatin hydrogels · Imperial
Tried and failed
multivalent cation crosslinking of biopolymer hydrogels applied to hydrogel bead synthesis. Outcome: unstable. Reason: insufficient polymer or crosslinker concentration failed to form stable gel network
The Valorization of Agricultural by Products for the Removal of Inorganic Phosphate from Water · Scholarship at UWindsor Institutional Repository
Tried and failed
increasing divalent crosslinker concentration applied to ionically crosslinked hydrogel capsules. Outcome: unstable. Reason: failed to prevent hydrogel dissolution during repeated physiological saline washes
Uncovering Biological Mechanisms of Immunomodulatory Biomaterials for Encapsulated Cell Therapies · MIT
Tried and failed
omitting thermal dry-annealing post-processing applied to freeze-thawed hydrogel substrate bonding. Outcome: unstable. Reason: lack of crystalline domain development leads to weak interfacial bonding and delamination upon swelling in water
Hydrogel Machines - Design, Manufacturing, and Applications · MIT
Tried and failed
polyacrylamide hydrogel immersed in deionized water applied to soft actuator electrolyte. Outcome: unstable. Reason: Samples became brittle within 12 hours due to swelling and dehydration instability
Tried and failed
gelatine hydrogel phantoms applied to extended underwater acoustic experiments. Outcome: unstable. Reason: the hydrogels disintegrated during extended immersion in water
Ultrasound-driven microbubble dynamics in microvessels · Imperial
Tried and failed
polysaccharide hydrogels under extreme acidic conditions applied to solar-driven water evaporation. Outcome: unstable. Reason: glucomannan degraded below pH 2, deteriorating hydrogel structure and lowering evaporation rate
Considered and rejected
Considered and rejected: Rejected using pure SF hydrogel for the vascularization layer due to rapid degradation and poor handling after 14 days compared to Ge/Col-I.
Bio-inspired materials for spinal cord regeneration · IRIS - UNITN - prod
Considered and rejected
Considered and rejected: Rejected hydrogels as the primary structural material for PIM bodies due to dehydration/shrinkage during storage, detachment of the sealing layer upon swelling, and payload leakage.
Bioinspired microrobotic systems for targeted and on-demand cargo delivery · Imperial
Considered and rejected
Considered and rejected: Rejected the standalone approach of dissolving humectants in hydrogels without coating, because the hydrogel continuously swells and deswells with ambient humidity fluctuations.
Soft Materials and Devices for Brain-Electronics Interface · Harvard
Considered and rejected
Considered and rejected: Rejected 0% aMAL (100% eMAL) hydrogels for in vivo vascularization studies due to previously established overly rapid hydrolytic degradation kinetics.
Synthetic Hydrogels for Islet Vascularization and Engraftment in the Subcutaneous Space · Georgia Tech
Precursor rheology and rapid gelation kinetics cause nozzle clogging and molding defects during fabrication
Precursors with excessive viscosity or overly fast crosslinking kinetics clogged delivery needles and microfluidic channels, preventing uniform extrusion and cell distribution. Other formulations suffered from insufficient viscosity to coat substrates, light attenuation that halted photopolymerization, or adhesion to molds that caused tearing upon release.
Tried and failed
trans-tissue photopolymerization of synthetic hydrogels applied to in situ hydrogel formation through tissue. Reason: Severe light attenuation through tissue and low reactive group density prevented polymerization
Engineered synthetic hydrogel platform for human intestinal organoids in vitro culture and in vivo therapeutic delivery · Georgia Tech
Tried and failed
increasing viscosity via polysaccharide blending before crosslinking applied to porous hydrogel networks. Outcome: worse than baseline. Reason: excessive viscosity hindered uniform crosslinker diffusion, causing inhomogeneous gelation and impaired transport properties
Tried and failed
dual-syringe delivery of fast-gelling hydrogel precursor applied to in situ hydrogel formulation. Reason: gelation occurred too rapidly inside the mixing nozzle, causing immediate clogging and preventing injection
Tried and failed
slow continuous needle insertion during fluid delivery applied to hydrogel tissue phantom. Reason: continuous needle movement caused lumen clogging, gel tearing, and void formation
Tried and failed
direct ink writing of polymer solutions applied to viscoelastic hydrogel ink formulation. Reason: low concentration loses shape fidelity while high concentration causes nozzle clogging
Considered and rejected
Considered and rejected: Rejected post-polymerization needle injection of macrophages into 3D muscle hydrogels due to leakage, cell loss, and non-uniform distribution across the construct.
Considered and rejected
Considered and rejected: Rejected centrifugal co-injection of hydrogel and spheroids due to high viscosity preventing proper settling and clogging the channels; transitioned to hydrostatic flow loading.
Development of Non-Invasive Technologies for Investigating Cardiac Tissue in a Novel Heart-on-Chip Platform · Publikationssystem UB Tuebingen
Considered and rejected
Considered and rejected: LOx-based hydrogel recipe formulation was rejected for ChOx biosensors because it lacked sufficient viscosity to reliably coat the electrode needle tip.
Tried and failed
plasma surface modification for demoulding release applied to photopolymerised micro-moulded hydrogels. Reason: insufficient anti-stiction without silanisation caused hydrogel tearing during mould release
Considered and rejected
Considered and rejected: Discontinuous dewetting was rejected for embossed hydrogel removal because it fails with high-molecular-weight, highly viscous biopolymers like hyaluronic acid
Macrophage-hitchhiking Anisotropic Microparticles for Therapeutic and Diagnostic Applications · MIT
Considered and rejected
Considered and rejected: Freeze-drying fabrication for hydrogels, rejected because porous structures collapse during water evaporation and reduce subsequent cyclic sorption.
Innovative Passive Cooling Strategies for Photovoltaic Modules · DSpace at SUNY Buffalo
Considered and rejected
Considered and rejected: Rejected standalone DN-gel test panel design due to mold deformation, hygienic issues, and stability issues, pivoting to polyester foam-infused hydrogels.
Sweating Building: A Study of Self-Cooling Hydrogels for Application in Adaptive Architecture · Harvard
Excessive matrix stiffness and high network density restrict cell proliferation, spreading, and tissue morphogenesis
Overly rigid hydrogel matrices and dense polymer networks physically confined encapsulated cells, suppressing cell spreading, focal adhesion formation, and division. The mechanical confinement overrode biochemical signaling, inhibited round spheroid assembly, and prevented cellular remodeling of the surrounding matrix.
Lost to a baseline
Elastic tissue culture plastic and polyacrylamide (pAAm) hydrogels failed to preserve the quiescent phenotype of HCFs (leading to increased myofibroblast activation) compared to viscoelastic AG hydrogels.
Engineered hydrogels with biomimetic biochemical and physical signaling cues for cardiac tissue engineering · IRIS - POLITO - prod
Lost to a baseline
Photocrosslinked tyramine-HA hydrogels exhibited lower cell spreading and lower focal adhesion strength in encapsulated MSCs compared to enzymatically crosslinked (HRP/H2O2) hydrogels at constant stiffness.
DESIGNING HYALURONIC ACID GRANULAR HYDROGELS FOR BIOMATERIALS APPLICATIONS · Penn
Lost to a baseline
GelMA hydrogels supported less rapid and extensive cell spreading of encapsulated hMSCs compared to norbornene-modified gelatin hydrogels
DESIGNING HYALURONIC ACID GRANULAR HYDROGELS FOR BIOMATERIALS APPLICATIONS · Penn
Considered and rejected
Considered and rejected: Rejected using higher density peptide hydrogels (8 mg/mL and 10 mg/mL) because increased stiffness restrained proliferating T cell clusters and reduced cell viability.
T cell activation and function investigated using fully-defined 3D culture · University of Nottingham Repository
Considered and rejected
Considered and rejected: Rejected using ECM hydrogel stiffness higher than 500 Pa for the tumor chamber, as high stiffness reduces T cell proliferation, infiltration, and cytotoxic activity markers.
Microphysiological Tumor-on-Chip Models Recapitulating Tumor-Microenvironment Interaction Applicable for Cell Therapy Testing · Publikationssystem UB Tuebingen
Considered and rejected
Considered and rejected: Rejected high-stiffness hydrogels (>10 kPa, e.g., 6% alginate/13% F127, 3A10G, 5A10G) because matrix stiffness restricted cell division and prevented round spheroid self-assembly
High throughput bioprinting of colorectal cancer tumour spheroids · Oxford
Tried and failed
increasing gelation pH of hydrogel scaffolds applied to cell-seeded collagen hydrogels. Reason: entangled fibril networks prevented cellular remodeling and lacunae formation
Tried and failed
exogenous growth factor addition in stiff hydrogels applied to endothelial cell sprout elongation. Outcome: no signal. Reason: matrix stiffness mechanical restriction overrides biochemical signaling from directly embedded growth factor
Biomaterial-driven lymphangiogenesis using click-crosslinked gelatin hydrogels · Imperial
Tried and failed
high-density cell encapsulation in hydrogel scaffolds applied to 3D tissue culture scaffold. Reason: Spatial constraints and cell crowding prevented cellular proliferation and growth within the matrix.
Toxic crosslinking agents, extreme pH conditions, and harsh processing reagents compromise cell viability
Exposure to non-physiological acidic or basic gelation pH, ultraviolet light irradiation, and reactive chemical crosslinkers caused severe cytotoxicity and DNA damage. Sacrificial template solvents and cytotoxic degradation reagents further led to significant cell loss and impaired cellular proliferation.
Tried and failed
Vinyl sulfone and acrylate hydrogel crosslinking applied to primary cell and lymphoma cell encapsulation. Reason: Cytotoxicity and slow gelation kinetics prevented cell survival in the hydrogel
Tried and failed
hydrogel polymerization at non-physiological pH applied to cell-laden collagen scaffolds. Reason: extreme acidic or basic gelation pH caused severe cytotoxicity and drastically reduced cell viability
Considered and rejected
Considered and rejected: Rejected using 50 mM TCEP for hydrogel degradation due to cell loss, reduced proliferation, and precipitation artifacts.
Wechselwirkungen zwischen hämatopoetischen Stamm- und Progenitorzellen und mesenchymalen Stamm- und Stromazellen in einer künstlichen Knochenmarksnische · Leibniz Universität Hannover Repository
Considered and rejected
Considered and rejected: UV-crosslinking hydrogels were rejected for dynamic stiffening due to UV- and crosslinker-induced DNA damage, cell toxicity, and cytoskeletal artifacts.
Passive nuclear uptake dynamics of small molecules in cancer · UT Austin
Considered and rejected
Considered and rejected: Rejected silver and gold nanoparticle-loaded conductive hydrogels due to particle oxidation/cytotoxicity (Ag) and precursor viscosity/lack of percolation conductivity (Au).
Development of an injectable hydrogel electrode for the treatment of ventricular arrhythmias · UT Austin
Considered and rejected
Considered and rejected: Rejected synthetic polymer sacrificial templates (PLA, PCL) for cellularized hydrogels due to cytotoxic evacuation solvents (chloroform/acetone) harming embedded cells
Endothelial Track Patterning for Directing Vascularization of Engineered Tissues · ResearchWorks
Considered and rejected
Considered and rejected: Rejected covalent hydrogel crosslinking due to potential lack of biological inertness and cross-reactivity with encapsulated proteins and cells.
Considered and rejected
Considered and rejected: Rejected PVA hydrogels due to biotoxicity of covalent cross-linkers and emulsion destabilisation by freeze-thaw cycles
Developing a combined microfluidic and hydrogen platform for single-cell assays · Oxford
Inadequate biodegradability and lack of bioactivity prevent cellular outgrowth and functional tissue integration
Scaffolds composed of non-hydrolyzable synthetic polymers or unmodified biopolymers failed to degrade in vivo, physically obstructing tissue repair and preventing defect bridging. Networks lacking cell-adhesive peptides or enzymatic crosslinking also failed to support cell outgrowth, organoid budding, and native matrix deposition.
Tried and failed
stem cell seeded synthetic hydrogel scaffolding applied to critical size volumetric muscle defects. Reason: hydrogel failed to degrade sufficiently and cells did not bridge the defect despite host engraftment
Aberrant Cellular Response and Muscle Regeneration Following Volumetric Muscle Loss · Georgia Tech
Tried and failed
agarose hydrogel encapsulation applied to neural tissue engineering implants. Outcome: no signal. Reason: failed to degrade in vivo, causing poor tissue integration and lack of functional recovery
Tried and failed
non-hydrolyzable synthetic polymer hydrogel scaffold delivery applied to cutaneous wound healing. Outcome: worse than baseline. Reason: the hydrogel failed to degrade, physically blocking and delaying tissue repair
Hydrogel-Delivery Of Mesenchymal Stem Cells To Modulate The Local Immune Environment And Direct Tissue Repair · Georgia Tech
Tried and failed
hydrogel without covalent enzymatic crosslinking applied to cell outgrowth in tissue engineering scaffolds. Reason: lack of enzymatic covalent stabilization failed to support cell outgrowth
ENGINEERING HYDROGEL MICROSTRUCTURE TO PROMOTE MENISCUS REPAIR · Penn
Tried and failed
hydrogel encapsulation of minced tissue fragments applied to cartilage tissue regeneration. Outcome: no signal. Reason: minimal cell outgrowth, lack of matrix deposition, and significant loss of initial glycosaminoglycans
Heparin-Based Hydrogel/3D Printed Scaffold Composites for Cartilage Regeneration · Georgia Tech
Lost to a baseline
Peptide-free LDTM hydrogels yielded a lower percentage of colonies forming budded organoids compared to peptide-functionalized degradable LDTM hydrogels.
Defined matrices for epithelial organoid culture and disease modelling · EPFL
Considered and rejected
Considered and rejected: Rejected pure unmodified alginate for the hydrogel matrix due to its poor in vivo degradability and lack of cell-adhesive properties.
NEW ADVANCED THERAPIES FOR DRUG DELIVERY IN CARDIAC REGENERATION. · IRIS - POLITO - prod
Tried and failed
partial enzymatic digestion of tissue fragments applied to cartilage regeneration scaffolds. Outcome: worse than baseline. Reason: enzymatic treatment depleted native glycosaminoglycans and failed to stimulate matrix deposition compared to isolated cells
Heparin-Based Hydrogel/3D Printed Scaffold Composites for Cartilage Regeneration · Georgia Tech
Weak interfacial bonding and contractual forces cause adhesive failure and hydrogel detachment
Highly crosslinked brittle networks and non-activated attachment interfaces exhibited lower lap shear adhesion than baseline glues and cracked under peel stress. In other cases, cellular contractile forces or fluid washes overcame interfacial bonding, causing hydrogels to peel from culture wells, microparticles to wash out, or coatings to detach from substrates.
Tried and failed
incorporating charged comonomers in hydrogel polymerization applied to tissue expansion hydrogels. Outcome: worse than baseline. Reason: caused structural fiber truncations during swelling and cyclic compression while reducing fatigue life
Scalable Subcellular Resolution Mapping of the Human Brain · MIT
Lost to a baseline
Hydrogels exhibited lower adhesive lap shear strength on human tissue (0.5 N/cm2) compared to fibrin glue baseline (0.6 ± 0.04 N/cm2).
In situ dissolvable hydrogels for biomedical applications · OpenBU
Tried and failed
cyanoacrylate adhesive bonding applied to hydrogel drug delivery interfaces. Outcome: worse than baseline. Reason: blocked drug diffusion transport and cracked/delaminated prematurely under mechanical peel stress
Tried and failed
hydrogel carrier for localized microparticle delivery applied to dynamic joint tissue defects. Reason: hydrogel adhesive failed to retain microparticles at the mechanical defect site, leading to rapid washout
BIOLOGIC DELIVERY TO PRESERVE JOINT HEALTH AND PROMOTE TISSUE REPAIR · Penn
Lost to a baseline
In lap shear testing, the BSAG control hydrogel was able to withstand a higher strain before adhesive failure compared to HA-MA-CHO-DCN due to the latter's brittle, highly crosslinked structure.
Design and Development of Modified Hyaluronic Acid Biopolymers Towards Biomedical Engineering Applications · Research Repository UCD
Considered and rejected
Considered and rejected: Rejected using mechanical interlocking alone for hydrogel coatings because soft, deformable hydrogels easily detach from microscale snap-fit connectors.
Hydrogel Machines - Design, Manufacturing, and Applications · MIT
Considered and rejected
Considered and rejected: Rejected non-activated polystyrene hanging basket/polyester struts because cellular contractile forces caused 100% of soft collagen hydrogels to detach from insert walls.
Building the colon epithelial microenvironment in vitro for investigation of intestinal disease mechanisms · ResearchWorks
Left open by the authors
Problems the authors named and did not get to.
Left open
Optimize in situ two-step stiffening of MeHA hydrogels using visible light or alternative crosslinkers to reduce cytotoxicity during cell culture. Blocker: Requires a wet chemistry and cell culture biology laboratory to synthesize hydrogels and evaluate cytotoxicity
Developing a hydrogel model to study the role of environmental factors on pulmonary fibroblasts · UT Austin
Left open
Develop protocols to culture live T cells in stage-specific hydrogels and perform viability, activation, and toxicity assays. Blocker: Requires a biological wet lab, live T cell cultures, and stage-specific hydrogel synthesis materials
Left open
Apply highly entangled hydrogels as biomimetic structural soft tissues such as muscle, cartilage, or wound dressings. Blocker: Requires wet lab fabrication, physical testing of hydrogels, and biological/tissue modeling apparatus.
Fracture of Complex Hydrogels: Dynamic and Microstructural Effects · Harvard
Left open
Develop secondary crosslinking or mechanical restraint methods to stabilize dynamic hydrogels against dissolution during long-term cell culture. Blocker: Requires a wet lab, chemical synthesis, hydrogel fabrication, and cell culture facilities
Investigating the stimuli responsiveness of reversible thia-conjugate addition crosslinked hydrogels · UT Austin
Left open
Overexpress integrin subunits, MMPs, PROX1, or VEGFR-3 in HDLECs to test for rescue of sprouting within stiff GelTN hydrogels. Blocker: Requires a wet biology lab, cell culture of HDLECs, genetic overexpression protocols, and hydrogel synthesis.
Biomaterial-driven lymphangiogenesis using click-crosslinked gelatin hydrogels · Imperial
Left open
Synthesize and evaluate APGD co-polymers to reduce in vitro cytotoxicity and tune mechanical properties for soft-hard interfaces. Blocker: Requires a wet chemistry and biomaterials lab for polymer synthesis, photocuring, mechanical testing, and in vitro cytotoxicity assays
3D Printed Biodegradable And Shape Memory Polymer Poly(Glycerol Dodecanedioate) (PGD) For Soft Tissue Reconstruction · Georgia Tech
Left open
Incorporate alternative adhesive ligands and cytokines into PEG-4MAL hydrogels to model immune responses in ovarian and colon cancers. Blocker: Requires a wet lab for biomaterial synthesis, PEG-4MAL hydrogel engineering, and in vitro cell culture
Biomaterial techniques to evaluate and engineer the tumor immune microenvironment in breast cancer and melanoma · Georgia Tech
Left open
Evaluate IL-2D hydrogels in antitumor immunotherapy driven by effector T cells in in vivo or in vitro models. Blocker: Requires wet lab facilities, synthesis of IL-2D hydrogels, and live cell/animal tumor models
Biomaterial-mediated approaches for persistent, localized, and targeted delivery of immunomodulatory proteins · Georgia Tech
Left open
Examine 3D cell-ECM interactions, fiber recruitment, and morphological behavior in tunable 3D ECM hydrogels or deformable scaffolds. Blocker: Requires wet-lab facilities for hydrogel synthesis, cell culture, tissue decellularization, and 3D microscopy
Left open
Design and conduct experiments to test the effect of poroelasticity on crack growth and fracture in hydrogels. Blocker: Requires a wet chemistry and mechanical testing laboratory to synthesize hydrogels and perform fracture experiments
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