Library · Materials, chemistry & fabrication
What Hydrogel Biomaterial Synthesis got wrong, from 85 theses
Summary written by a model from the records below: The records describe various challenges encountered in the synthesis, crosslinking, and functional application of hydrogel biomaterials. These difficulties include inadequate mechanical robustness, rapid degradation or excessive persistence, processing and injection clogs, reagent cytotoxicity, and diminished bioactivity relative to native tissue matrices. These records come from graduate theses, 2021 to 2026, each labeled with its degree where the repository states it, and 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.
Plus 9 problems the authors left open, listed at the end.
Failure modes, by theses reporting them
Select a mode to jump to its records.
Hydrogels exhibit mechanical weakness, brittleness, and poor interfacial adhesion under physical loading
Formulations frequently suffer from lower compressive and tensile moduli, brittle fracture under low strain, and catastrophic crack propagation compared to composites or natural baselines. They also tear at gripping interfaces and delaminate upon swelling due to insufficient crystalline development or weak physical interlocking.
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 · PhD
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 · Nottingham · PhD
Lost to a baseline
CaCO3-crystallized PDE(500) hydrogels had lower storage modulus and higher brittleness than the intermediate Ca2+-doped hydrogels
Reinforcement of Hydrogels via Polyacrylic Acid Nanoparticles Induced Calcium Carbonate Crystallization · University of Nevada, Reno · Master's
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 · University College Dublin · PhD
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 · TU Wien · PhD
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 · Boston University · PhD
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 · PhD
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 · Nottingham · PhD
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 · Saskatchewan · PhD
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 · Johns Hopkins · PhD
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 · PhD
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 · University College Dublin · PhD
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 · University College Dublin · PhD
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 · PhD
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 · PhD
Lost to a baseline
Silk granular hydrogels exhibited substantially lower tensile strain at failure (29–62%) compared to neat PEGDM and composites (>90%)
Hybrid hydrogels for load-bearing implants · EPFL · PhD
Lost to a baseline
PVA hydrogels with 0.5 mm sharp cracks exhibited lower tensile fatigue nominal stress thresholds (0.1082 MPa for 2 FT, 0.1865 MPa for 4 FT) compared to samples with 4 mm cylindrical holes (0.2274 MPa for 2 FT, 0.5812 MPa for 4 FT)
Tensile Fatigue Characterization of High Strength Hydrogels for Soft Tissue Applications · Duke · Doctorate
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.
Towards engineering living functional materials · MIT · PhD
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
Hybrid hydrogels for load-bearing implants · EPFL · PhD
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 · PhD
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 · PhD
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 · PhD
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.
Design and Development of Injectable, Tough and Intrinsically-Adhesive Hydrogels for Biomedical Applications · EPFL · PhD
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.
Multiscale design of bioadhesive platforms for next-generation applications in surgery and healthcare · MIT · PhD
Insufficient crosslinking density leads to premature degradation, matrix dissolution, and mechanical collapse
Low precursor concentrations, inadequate initiator levels, or highly labile bonds cause hydrogels to degrade far faster than intended under physiological or environmental conditions. This deficient network formation results in uncontrolled swelling, premature structural dissolution, rapid drug burst release, and complete loss of handling integrity.
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 · PhD
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 · PhD
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
Towards a Non-Invasive Model for Women’s Uterine Health: From Transcriptional Programs to Tissue Assembly · Harvard · PhD
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
Enhanced bio-minerals production using catalysts to accelerate resource recovery in wastewater treatment plants. · Cranfield · PhD
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 · PhD
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 · PhD
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 · University of Camerino · PhD
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 · PhD
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 · PhD
Tried and failed
low crosslinking density hydrogels applied to sustained protein drug delivery. Reason: mesh size was too large, causing rapid burst release within hours
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 · PhD
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 · PhD
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 · University of Windsor · PhD
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 · PhD
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
VASCULARIZATION OF BIOENGINEERED FAT WITH TUNABLE MATRIX PROPERTIES FOR MACRO-PERFUSION AND SOFT TISSUE RECONSTRUCTION · Cornell · PhD
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
An Artificial Sphincter based on Dielectric Elastomer Actuators in the context of Urinary Incontinence · EPFL · PhD
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 · PhD
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
Materials design and surface engineering of functional hydrogels for solar desalination and water purification · UT Austin · PhD
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 · University of Trento · PhD
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 · PhD
Unfavorable rheology and rapid gelation kinetics cause fabrication, injection, and molding failures
Precursors with excessive viscosity or overly fast crosslinking clog injection nozzles, block microfluidic channels, and prevent homogeneous distribution. In addition, weak prepolymers lose shape fidelity during printing, tear during demolding without proper release agents, or detach from walls due to cell-mediated contraction.
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 · PhD
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 · PhD
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 · PhD
Considered and rejected
Considered and rejected: Rejected direct manual pipetting for high-throughput 3D culture viability studies of CTX cell-laden ECM hydrogels over extended periods due to soft hydrogel matrix contraction.
Development of a bioactive ECM hydrogel to modulate inflammation and facilitate stem cell delivery after traumatic brain injury · Imperial · PhD
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
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
Materials design and surface engineering of functional hydrogels for solar desalination and water purification · UT Austin · PhD
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
From heterotopic ossification to fracture healing: identifying and delivering adjuvants to modulate bone formation · Imperial · PhD
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
A remotely operable convection-enhanced thermo-therapy catheter system for broad distribution of therapeutics in the brain · UT Austin · PhD
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
Multiscale design of bioadhesive platforms for next-generation applications in surgery and healthcare · MIT · PhD
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.
Mechano-immuno-therapy for Skeletal Muscle Repair · Harvard · PhD
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 · Tübingen · PhD
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.
Development of a microfluidic biosensing system for real-time monitoring of acetylcholinesterase activity · Imperial · PhD
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 · PhD
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
Development of a micro-patterned hydrogel scaffold to guide photoreceptor polarization for treatment of macular degeneration · Imperial · PhD
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 · PhD
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 · University at Buffalo · PhD
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 · Master's
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 · University of Washington · PhD
Excessive stiffness, dense crosslinking, and non-degradable matrices impede cell growth and tissue remodeling
Highly crosslinked, overly stiff, or non-degradable hydrogels restrict cell division, cluster expansion, and round spheroid self-assembly by creating rigid physical boundaries. Without degradable motifs or appropriate matrix compliance, encapsulated cells fail to spread, migrate, or deposit new extracellular matrix to repair tissue defects.
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 · PhD
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 · PhD
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 · Politecnico di Torino · PhD
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 · PhD
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 · PhD
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 · PhD
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 · Nottingham · PhD
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. · Politecnico di Torino · PhD
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 · Tübingen · PhD
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 · PhD
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
ENHANCING BIOCHEMICAL, STRUCTURAL, MECHANICAL PROPERTIES OF TISSUE-ENGINEERED MENISCI AND ENTHESES USING BIOCHEMICAL AND BIOMECHANICAL STIMULI · Cornell · PhD
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.
Development of a three-dimensional in vitro vascularized human skin equivalent employing collagen/keratin hydrogels · UT Austin · PhD
Synthetic and modified hydrogels show inferior bioactivity and functional performance compared to standard baselines
Engineered hydrogels often underperform relative to native matrices like Matrigel or fibrin in promoting organoid formation efficiency, endothelial network assembly, and chondrogenic expression. Furthermore, hydrogel coatings can create diffusion barriers that diminish drug penetration or fail to retain therapeutics at dynamic defect sites.
Tried and failed
hydrogel substrate conditioning of stem cell secretome applied to in vitro myogenic differentiation assay. Outcome: worse than baseline. Reason: hydrogel-stimulated conditioned media failed to improve myotube formation over tissue culture plastic controls
Culture systems for controlling mesenchymal stromal cell, protein, and cell-secreted protein release · Georgia Tech · PhD
Tried and failed
combining decellularised extracellular matrix hydrogel with stem cells applied to traumatic brain injury repair. Outcome: worse than baseline. Reason: combination therapy lacked synergistic effects and performed worse than standalone hydrogel or cell treatments
Development of a bioactive ECM hydrogel to modulate inflammation and facilitate stem cell delivery after traumatic brain injury · Imperial · PhD
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 · PhD
Lost to a baseline
Sow endometrial ECM hydrogel performed significantly worse than Matrigel baseline in supporting endometrial organoid formation efficiency.
Extracellular matrix hydrogels for endometrial regeneration · Imperial · PhD
Lost to a baseline
Supernatant from degraded LST-VPM-Cys hydrogels showed minimal activity, underperforming commercial lysostaphin diffused from hydrogels
Design and Characterization of Modified Lytic Enzymes and Nanoparticle-Based Vaccines to Combat S. aureus · Georgia Tech · PhD
Lost to a baseline
Progenitor organoids in 4, 6, and 8 mg/ml ECM hydrogels showed significantly lower DNA recovery and proliferation at day 10 compared to gold standard BME2 matrix.
From semi-synthetic to natural biomaterials: a journey to the development of an optimized in-vitro model for liver tissue engineering · Nottingham · PhD
Lost to a baseline
In vitro endothelial cell network parameters (network percentage area, junction density, and total network length) in GFOGER-functionalized PEG-4MAL hydrogels were significantly lower than natural fibrin gel controls (p < 0.0001, p = 0.0115, and p = 0.0030, respectively).
Synthetic Hydrogels for Islet Vascularization and Engraftment in the Subcutaneous Space · Georgia Tech · PhD
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 · PhD
Lost to a baseline
CBD-loaded Aeroperl 300 coated with carbomer resulted in lower mucosal penetration (3.91 ± 1.54 µg/cm2, PE 0.33) than pure CBD (11.70 ± 3.70 µg/cm2, PE 1.00) due to hydrogel barrier formation.
Development of mucoadhesive carrier systems for flavoring agents and cannabidiol · Tübingen · PhD
Lost to a baseline
Directly incubated IL-4 releasing hydrogels yielded lower CCL-22 secretion compared to a 404 ng IL-4 bolus injection in M0 and M1 conditions.
Additive manufacturing of affinity hydrogels for controlled biomacromolecule delivery in early osteoarthritis · Nottingham · PhD
Lost to a baseline
4 wt% pAAm hydrogel (µb = 0.1-0.14) did not lubricate cartilage as effectively as high-molecular weight partially hydrophobic forms of HA (µb = 0.05-0.1).
Enhancing Joint Health: Tribological Characterization of Lubricants for Articular Cartilage · Cornell · PhD
Lost to a baseline
Pellet culture control promoted higher chondrogenic marker gene expression (COL2) than 7.5% and 10% gelMA hydrogels at low (1 ng/mL) TGF-β3 levels.
Hydrogels in 3D bioprinting and tissue engineering Hydrogele im Bereich 3D Bioprinting und Tissue Engineering · TU Wien · PhD
Crosslinking chemistries, harsh processing conditions, and toxic additives induce severe cell mortality
Chemical crosslinking agents, extreme gelation pH values, and ultraviolet light exposure cause substantial cytotoxicity, DNA damage, and cytoskeletal artifacts in encapsulated cells. Residual reducing agents, oxidative metal nanoparticles, and harsh template removal solvents further reduce cell viability and generate biological incompatibilities.
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
Immune Organoids to Study Antigen Presentation · Cornell · PhD
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
ENHANCING BIOCHEMICAL, STRUCTURAL, MECHANICAL PROPERTIES OF TISSUE-ENGINEERED MENISCI AND ENTHESES USING BIOCHEMICAL AND BIOMECHANICAL STIMULI · Cornell · PhD
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 · PhD
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 · PhD
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 · PhD
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 · University of Washington · PhD
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.
Synthesis and evaluation of polymer mosaics as highly tunable biomaterials for biomedical applications · Boston University · PhD
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 · PhD
Hydrogels suffer from dehydration, storage shrinkage, and uncontrolled ambient swelling fluctuations
Standalone hydrogels dehydrate and lose moisture rapidly within hours in open air, leading to structural shrinkage, payload leakage, and delamination of protective coatings. Additionally, they experience continuous swelling and deswelling in response to ambient humidity fluctuations while failing to replicate porous tissue mechanics.
Considered and rejected
Considered and rejected: Single-layer and multi-layer gelatin hydrogel phantoms rejected in favor of poroelastic sponge-gel composites because hydrogels cannot capture tissue porosity and cause unrealistic liquid regurgitation.
Hydrodynamics of needle-free jet injections · Texas Tech · PhD
Lost to a baseline
PDMS dip-coating restrained hydrogel swelling capacity much more severely (down to ~20% mass uptake) compared to prior laser-perforated silicone sleeves (60-70% retention).
Bilateral swelling self-inflating tissue expanders · Oxford · PhD
Considered and rejected
Considered and rejected: Rejected the standalone approach of coating hydrogels with hydrophobic elastomers (e.g. PDMS), as 1-mm-diameter fibers dehydrate within hours in open air.
Soft Materials and Devices for Brain-Electronics Interface · Harvard · PhD
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 · PhD
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 · PhD
Considered and rejected
Considered and rejected: Rejected hydrogel casting materials (agarose, gelatin, PVA-C, PAA) due to short lifespan (<1-3 years), vulnerability to puncture degradation, dehydration, and freezing cycle requirements.
Soft liver phantom with a hollow biliary system · Tübingen · PhD
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 · PhD
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 · PhD
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 · PhD
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 · PhD
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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 · PhD
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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 · PhD
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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 · PhD
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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
LEVERAGING BIOLOGICAL INSIGHT FROM THE REGENERATIVE MRL/MPJ MOUSE STRAIN FOR TENDON MECHANISTIC DISCOVERY AND GUIDING THERAPEUTIC DEVELOPMENT · Cornell · PhD
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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
Fracture of Highly Entangled Polymer Networks · Harvard · PhD
Who has worked on this
Authors of the public theses cited on this page, most-cited first.
- Victoria Grace Muir · Penn · PhD · 2022
DESIGNING HYALURONIC ACID GRANULAR HYDROGELS FOR BIOMATERIALS APPLICATIONS - Sarah J. Wu · MIT · PhD · 2024
Multiscale design of bioadhesive platforms for next-generation applications in surgery and healthcare - Dana E. Al-Ansari · Imperial · PhD · 2024
Biomaterial-driven lymphangiogenesis using click-crosslinked gelatin hydrogels - Michelle Javier Quizon · Georgia Tech · PhD · 2024
Synthetic Hydrogels for Islet Vascularization and Engraftment in the Subcutaneous Space - Rijian Song · University College Dublin · PhD · 2024
Tough Injectable Hydrogels by Combining Elastic and Energy Dissipation - Alain Vella · Imperial · PhD · 2023
Mechanical tension in pancreatic ductal adenocarcinoma progression - Martina Genta · Imperial · PhD · 2023
An engineered biosynthetic hydrogel for 3D neural tissue interfaces - Jongkil Kim · Cornell · PhD · 2022
ENHANCING BIOCHEMICAL, STRUCTURAL, MECHANICAL PROPERTIES OF TISSUE-ENGINEERED MENISCI AND ENTHESES USING BIOCHEMICAL AND BIOMECHANICAL STIMULI - Charlotte Lee-Reeves · Imperial · PhD · 2022
Development of a bioactive ECM hydrogel to modulate inflammation and facilitate stem cell delivery after traumatic brain injury - Julian Heck · Imperial · PhD · 2022
Design of printable electroactive biomaterials for tissue engineering - Xinyue Liu · MIT · PhD · 2022
Hydrogel Machines - Design, Manufacturing, and Applications - Paul Claude Henri Le Floch · Harvard · PhD · 2021
Soft Materials and Devices for Brain-Electronics Interface
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