Hyaluronic Acid Hydrogels Crosslinked in Physiological Conditions: Synthesis and Biomedical Applications
Abstract
:1. Introduction
2. Overview of HA Crosslinking Reactions Carried out at Physiological Conditions
2.1. Boronic-Ester Formation
2.2. Schiff-Base Formation
2.3. Thiol Chemistry
2.4. Cycloaddition Reactions
2.4.1. Azide-Alkyne Cycloaddition Reaction
2.4.2. Diels–Alder Formation
3. Thermoreversible Gelation of HA Hydrogels at Physiological Temperature
Combination with Natural Polymers
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Abbreviation | Name |
ADH | Adipic acid dihydrazide |
ASCs | Adipose-derived stem cells |
pKa | Acid dissociation constant |
HA-AA | Azide-modified HA |
BP | BMP-2 mimicking peptide |
CEC | Carboxyethyl-chitosan |
CPCs | Cartilage-derived progenitor cells |
CS | Chitosan |
Dex | Dextran |
Dexa | Dexamethasone |
DA | Diels-Alder |
Dox | Doxorubicin |
DHCA | Dihydrocaffeic acid |
DVS | Divinyl sulfone |
ECM | Extracellular matrix |
EWG | Electron withdrawing group |
Fru | Fructose |
GP | Glycerophosphate |
GC | Glycol Chitosan |
GLU | Gluconamide |
HA | Hyaluronic acid |
HA-tet | HA-tetrazine |
HA-TCO | HA- trans-cyclooctene |
hMSC | Human mesenchymal stem cells |
BMP-2 | Human bone morphogenetic protein 2 |
HPCH | Hydroxypropyl chitin |
IEDDA | Inverse electron demand Diels-Alder |
G‘‘ | Loss Modulus |
LCST | Low critical solution temperature |
Mal | Maltose |
HA-mCOH | Mono-aldehyde HA |
NIPA | N-isopropylacrylamide |
CS-OB | Oxanorbonadiene-modified CS |
OHA | Oxidized Hyaluronic acid |
PBA | Phenylboronic acid |
PECs | Polyelectrolyte complexes |
PEG | Polyethylene glycol |
PEGDA | Polyethylene glycol di-acrylate |
PEGDMA | Polyethylene glycol di-methacrylate |
PEO | Poly (ethylene oxide) |
PNIPAm | Poly (N-isopropylacrylamide) |
PPO | Poly (propylene oxide) |
QbD | Quality by design approach |
ROS | Reactive Oxygen Species |
NaOH | Sodium hydroxide |
NaIO4 | sodium periodate |
T | Temperature |
SH | Thiol group |
3D | Three-dimensional |
G’ | Storage Modulus |
SPAAC | Strain-promoted azide–alkyne cycloaddition |
UV | Ultraviolet |
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Cross-Linking | Complementary Groups | HA Chemical Modification | Biomedical Applications |
---|---|---|---|
Boronic–ester formation | Boronic acid + amine/hydroxyl [36,42,43,45,47] | Amidation [36,42,43,45,47]; | Injectable [36,45]; biomaterial inks [36]; tissue engineering [36]: bone; ROS-responsive properties [36]; drug release [43] |
Schiff base formation | Amine + Aldehyde [51,53,54,55,59] | Oxidation [51,53,54,55]; Amidation [59,61]; | Injectable [51,53,54,55,59,61]; tissue engineering [59]: bone [54], cartilage [53,55]; Bioprinting [55]; pH responsive property [51]; drug release [51]; vitreous substitute [61] |
Dihydrazide + Aldehyde + [56,59] | |||
Oxyamine + aldehyde/Ketone [61] | |||
Thiol Chemistry | |||
Disulfide formation/exchange | Thiol-thiol [62,63,64,74,75] | Amidation [62,63,64,74] | Tissue engineering [62,63,64] |
Michael addition | Thiol + (metha)/acrylate [72,73,74,75,76,77,84] | Amidation [72,74,77,78,79,81,85]; ether formation [80] | Injectable [77,78,81,84]; tissue engineering [72,73,77,84]: cartilage [79,81]; cell encapsulation [84]; wound healing [72]; hemostasis [85] |
Thiol + Melaimide [78,79] | |||
Thiol + Vinyl-sulfone [80,81] | |||
Thiol + Catechol [85] | |||
Thiol-yne coupling | Thiol/yne [83] | Amidation [83] | Injectable [83]; cell encapsulation [83]; tissue engineering: cartilage [83] |
Cycloaddition reaction | |||
Azide–alkyne cycloaddition reaction | Azide + Oxanorbornadiene [89] | Amidation [89,90,91] | Injectable [89,90,91]; tissue engineering [89]; cell encapsulation [90,91] |
Azide + Cyclooctyne [90,91] | |||
Diels–Alder formation | Furan + Maleimide [97,103] | Amidation [97,98,99,100,101,102,103] | Injectable [98,99,100,103]; tissue engineering [99,103]: bone [100]; rheumatoid arthritis [99]; cell encapsulation [97]; protein encapsulation [101]; drug release [98,99] |
Tetrazine + Trans-cyclooctene [98,99,100] | |||
Tetrazine + norbornene [101,102] |
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Pérez, L.A.; Hernández, R.; Alonso, J.M.; Pérez-González, R.; Sáez-Martínez, V. Hyaluronic Acid Hydrogels Crosslinked in Physiological Conditions: Synthesis and Biomedical Applications. Biomedicines 2021, 9, 1113. https://doi.org/10.3390/biomedicines9091113
Pérez LA, Hernández R, Alonso JM, Pérez-González R, Sáez-Martínez V. Hyaluronic Acid Hydrogels Crosslinked in Physiological Conditions: Synthesis and Biomedical Applications. Biomedicines. 2021; 9(9):1113. https://doi.org/10.3390/biomedicines9091113
Chicago/Turabian StylePérez, Luis Andrés, Rebeca Hernández, José María Alonso, Raúl Pérez-González, and Virginia Sáez-Martínez. 2021. "Hyaluronic Acid Hydrogels Crosslinked in Physiological Conditions: Synthesis and Biomedical Applications" Biomedicines 9, no. 9: 1113. https://doi.org/10.3390/biomedicines9091113
APA StylePérez, L. A., Hernández, R., Alonso, J. M., Pérez-González, R., & Sáez-Martínez, V. (2021). Hyaluronic Acid Hydrogels Crosslinked in Physiological Conditions: Synthesis and Biomedical Applications. Biomedicines, 9(9), 1113. https://doi.org/10.3390/biomedicines9091113