Design of Bio-Conjugated Hydrogels for Regenerative Medicine Applications: From Polymer Scaffold to Biomolecule Choice
Abstract
:1. Introduction
2. General Factors Influencing The Design of Hydrogels for Regenerative Medicine
2.1. Biocompatibility
2.2. Gelling and Mechanical Properties
2.3. Architecture and Shape
2.4. Porosity and Network Density
2.5. Degradability
3. Synthetic Criteria for Hydrogel Production
3.1. Polymer Choice
3.2. Polymerization Conditions
4. Introduction of Biomolecules within the Hydrogel Network
4.1. Covalent Tethering of Biomolecules
4.2. Supramolecular Tethering of Biomolecules
4.3. Uncontrolled Release of Biomolecules from Hydrogel Networks
4.4. ‘On Demand’ Release of Biomolecules from Hydrogels Networks
5. Biomolecules for Tissue Regeneration
5.1. Nucleics Acids Conjugated to Synthetic Hydrogels
5.2. Proteins Conjugated to Synthetic Networks
5.3. Carbohydrates Conjugated to Synthetic Hydrogels
5.4. Peptides Conjugated to Synthetic Hydrogels
6. Conclusions and Future Perspectives
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Abbreviation | Full Name |
Acs | Acetyl CoA Synthease |
ATRP | Atom Transfer Radical Polymerization |
°C | Degree Celsius |
CGC | Critical Gelation Concentration |
CL | Cross-linker |
CMP | Collagen Mimetic Peptide |
Cryo-SEM | Cryo-Scanning Electron Microscope |
DAMA | N-(N′,N′-dicarboxymethyl aminopropyl) methacrylamide |
DMSO | Dimethyl sulfoxide |
DNA | Deoxyribonucleic acid |
DTT | Dithiothreitol |
EtOH | Ethanol |
Fmoc | Fluorenylmethyloxycarbonyl chloride |
G’ | Storage Modulus |
GF | Growth Factor |
H2O | Water |
hMSCs | Human Mesenchymal Stem Cells |
HPMA | Hydroxypropyl methacrylate |
IA | Itaconic acid |
J | Joule |
kPa | KiloPascal |
LBM | Load Bearing Molecule |
LCST | Lower Critical Solution Temperature |
mAB | Monoclonal Anti Bodies |
MADIX | Macromolecular Design by Interchange of Xantates |
MeOH | Methanol |
mm | Millimeter |
NHS | N-Hydroxysuccinimide |
nm | Nanometer |
PAAc | Poly(acrylic acid) |
PAAm | Poly(acryl amide) |
PCL | Poly(ε-caprolactone) |
PDMAEMA | Poly(2-(dimethylamino)ethyl methacrylate) |
PHEMA | Poly(2-hydroxyethyl methacrylate) |
PHPMA | Poly(2- hydroxypropyl methacrylate) |
PEG | Poly(ethylene glycol) |
PEI | Poly(ethylene imine) |
PEODA | Poly(ethyleneoxide) diacrylate |
PGA | Poly(glycolic acid) |
PLA | Poly(lactic acid) |
PLGA | Poly(lactic-glycolic acid) |
PMOXA | Poly(2-methyl-2-oxazoline) |
PNIPAM | Poly(N-ispropylacrylamide) |
PNIPMAM | Poly(N-isopropylmethacrylamide) |
PNVP | Poly(N-vinylpyrrolidone) |
PPO | Poly(propylene oxide) |
PU | Poly(urethane) |
PVA | Poly(vinyl alcohol) |
PVCL | Poly(vinyl caprolactam) |
RAFT | Reversible Addition Fragmentation Chain Transfer |
RGD | Arginylglycylaspartic acid |
ROMP | Ring-Opening Metathesis Polymerization |
T | Temperature |
UCST | Upper Critical Solution Temperature |
UV | Ultra Violet |
VPTT | Volume Phase Transition Temperature |
Wt% | Weight % |
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Polymer | Abbreviation | Structure | Properties | Applications | Refs. |
---|---|---|---|---|---|
Poly(2-hydroxyethyl methacrylate) | PHEMA | Hydrophilic, biocompatible | cell growth; tissue engineering; regenerative medicine | [134,135,136] | |
Poly(2-hydroxypropyl methacrylate) | PHPMA | Hydrophilic, biocompatible | cell growth; tissue regeneration | [125] | |
Poly(ethylene glycol)/poly(ethylene oxide) | PEG/PEO | Hydrophilic, biocompatible | cell growth; tissue engineering; regenerative medicine | [137,138] | |
Poly(2-methyl-2-oxazoline) | PMOXA | Hydrophilic, biocompatible | cell growth; tissue regeneration | [139,140] | |
Poly(vinyl alcohol) | PVA | Hydrophilic, biocompatible | tissue engineering; regenerative medicine | [141,142,143] | |
Poly(acrylic acid) | PAAc | Hydrophilic, pH-responsive | cell growth | [144] | |
Poly [2-(dimethylamino)ethyl methacrylate] | PDMAEMA | Hydrophilic, pH-responsive | biomolecule delivery, regenerative medicine | [145,146] | |
Poly(ethylenimine) | PEI | Hydrophilic, pH-responsive | biomolecule delivery | [147,148] | |
Poly(acrylamide) | PAAm | Hydrophilic, biocompatible | antigen sensing, regenerative medicine | [149] | |
Poly(N-vinyl pyrrolidone) | PNVP | Hydrophilic, biocompatible | biomolecule delivery; tissue engineering | [150] | |
Poly(N-isopropyl acrylamide) | PNIPAM | Hydrophilic, biocompatible, temperature responsive | biomolecule delivery; cell growth; tissue engineering | [145,151] | |
Poly(ε-caprolactone) | PCL | Hydrophobic, biodegradable | cell growth; tissue engineering | [152,153] | |
Poly(lactic acid) | PLA | Hydrophobic, biodegradable, biocompatible | biomolecule delivery; tissue engineering | [154] | |
Poly(glycolic acid) | PGA | Slightly hydrophilic, biodegradable | Biomolecule delivery; tissue engineering | [155,156,157] | |
Poly(N-vinylcaprolactam) | PVCL | Hydrophobic, biocompatible, temperature responsive | Biomolecule delivery; theranostic; tissue engineering | [158,159,160] |
Biomolecule | Conjugation Methods | Applications | Refs. |
---|---|---|---|
Oligonucleotides | Covalent attachment, non-covalent crosslinking, electrostatic interactions | Drug delivery, cell culture | [171,172,173,174] |
Proteins (GFs, enzymes) | Covalent attachment, non-covalent crosslinking (host-guest chemistry), electrostatic interactions | tissue regeneration | [175,176,177,178] |
Carbohydrates | Covalent attachment, non-covalent attachment | tissue regeneration | [179,180] |
Peptides | Covalent attachment | tissue adhesives, regeneration | [181,182,183,184] |
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Chimisso, V.; Aleman Garcia, M.A.; Yorulmaz Avsar, S.; Dinu, I.A.; Palivan, C.G. Design of Bio-Conjugated Hydrogels for Regenerative Medicine Applications: From Polymer Scaffold to Biomolecule Choice. Molecules 2020, 25, 4090. https://doi.org/10.3390/molecules25184090
Chimisso V, Aleman Garcia MA, Yorulmaz Avsar S, Dinu IA, Palivan CG. Design of Bio-Conjugated Hydrogels for Regenerative Medicine Applications: From Polymer Scaffold to Biomolecule Choice. Molecules. 2020; 25(18):4090. https://doi.org/10.3390/molecules25184090
Chicago/Turabian StyleChimisso, Vittoria, Miguel Angel Aleman Garcia, Saziye Yorulmaz Avsar, Ionel Adrian Dinu, and Cornelia G. Palivan. 2020. "Design of Bio-Conjugated Hydrogels for Regenerative Medicine Applications: From Polymer Scaffold to Biomolecule Choice" Molecules 25, no. 18: 4090. https://doi.org/10.3390/molecules25184090