In Situ‐Forming Cross‐linking Hydrogel Systems: Chemistry and Biomedical Applications

Bi, Xiangdong; Liang, Aiye

doi:10.5772/63954

Cited by 15 publications

(10 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A final demand is that the cross-linker must be selective for its counterpart to avoid off-target reactions with the protein cargo as well as proteins in the tissue of the injection site. Hence, reactions that are susceptible to amine structures or nucleophiles like Schiff-base reactions, genipin coupling, β-aminoacrylate formation, and o -phthalaldehyde condensation pose too great a risk of interacting with proteins or body tissues. − …”

Section: Introductionmentioning

confidence: 99%

In Situ Forming iEDDA Hydrogels with Tunable Gelation Time Release High-Molecular Weight Proteins in a Controlled Manner over an Extended Time

et al. 2021

View full text Add to dashboard Cite

Off-target interactions between reactive hydrogel moieties and drug cargo as well as slow reaction kinetics and the absence of controlled protein release over an extended period of time are major drawbacks of chemically cross-linked hydrogels for biomedical applications. In this study, the inverse electron demand Diels−Alder (iEDDA) reaction between norbornene-and tetrazine-functionalized eight-armed poly(ethylene glycol) (PEG) macromonomers was used to overcome these obstacles. Oscillatory shear experiments revealed that the gel point of a 15% (w/v) eight-armed PEG hydrogel with a molecular weight of 10 kDa was less than 15 s, suggesting the potential for fast in situ gelation. However, the high-speed reaction kinetics result in a risk of premature gel formation that complicates the injection process. Therefore, we investigated the effect of polymer concentration, temperature, and chemical structure on the gelation time. The cross-linking reaction was further characterized regarding bioorthogonality. Only 11% of the model protein lysozyme was found to be PEGylated by the iEDDA reaction, whereas 51% interacted with the classical Diels−Alder reaction. After determination of the mesh size, fluorescein isothiocyanate−dextran was used to examine the release behavior of the hydrogels. When glucose oxidase was embedded into 15% (w/v) hydrogels, a controlled release over more than 250 days was achieved. Overall, the PEG-based hydrogels cross-linked via the fast iEDDA reaction represent a promising material for the long-term administration of biologics.

show abstract

Section: Introductionmentioning

confidence: 99%

In Situ Forming iEDDA Hydrogels with Tunable Gelation Time Release High-Molecular Weight Proteins in a Controlled Manner over an Extended Time

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In recent years click chemistry, characterized by its high reactivity, selectivity, and yield, appears as the most promising strategy for the development of hydrogel under mild conditions. In addition, its unique bioorthogonality allows for gentle and efficient encapsulation of several bioactives onto the formed hydrogels [ 22 , 23 , 24 ].…”

Section: Overview Of Ha Crosslinking Reactions Carried Out At Physiological Conditionsmentioning

confidence: 99%

Hyaluronic Acid Hydrogels Crosslinked in Physiological Conditions: Synthesis and Biomedical Applications

et al. 2021

View full text Add to dashboard Cite

Hyaluronic acid (HA) hydrogels display a wide variety of biomedical applications ranging from tissue engineering to drug vehiculization and controlled release. To date, most of the commercially available hyaluronic acid hydrogel formulations are produced under conditions that are not compatible with physiological ones. This review compiles the currently used approaches for the development of hyaluronic acid hydrogels under physiological/mild conditions. These methods include dynamic covalent processes such as boronic ester and Schiff-base formation and click chemistry mediated reactions such as thiol chemistry processes, azide-alkyne, or Diels Alder cycloaddition. Thermoreversible gelation of HA hydrogels at physiological temperature is also discussed. Finally, the most outstanding biomedical applications are indicated for each of the HA hydrogel generation approaches.

show abstract

“…Gels have been used as wound dressings, vitreous substitutes and regenerative medicine [ 140 ]. Polymers commonly used in these systems include PLGA, PEG, poly(vinylpyrrolidone) (PVP), hyaluronic acid or hyaluronan (HA), poly(acrylamide) and collagen [ 141 ], as well as natural polymers, such as chitosan, xanthan gum, guar gum and carrageenan [ 142 ]. Drug release and degradation mechanisms are dependent on matrix characteristics such as mesh size, mechanical strength and interactions with the protein cargo [ 143 ].…”

Section: General Strategies To Increase Duration Of Actionmentioning

confidence: 99%

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

et al. 2020

View full text Add to dashboard Cite

Proteins and peptides have emerged in recent years to treat a wide range of multifaceted diseases such as cancer, diabetes and inflammation. The emergence of polypeptides has yielded advancements in the fields of biopharmaceutical production and formulation. Polypeptides often display poor pharmacokinetics, limited permeability across biological barriers, suboptimal biodistribution, and some proclivity for immunogenicity. Frequent administration of polypeptides is generally required to maintain adequate therapeutic levels, which can limit efficacy and compliance while increasing adverse reactions. Many strategies to increase the duration of action of therapeutic polypeptides have been described with many clinical products having been developed. This review describes approaches to optimise polypeptide delivery organised by the commonly used routes of administration. Future innovations in formulation may hold the key to the continued successful development of proteins and peptides with optimal clinical properties.

show abstract

In Situ‐Forming Cross‐linking Hydrogel Systems: Chemistry and Biomedical Applications

Cited by 15 publications

References 119 publications

In Situ Forming iEDDA Hydrogels with Tunable Gelation Time Release High-Molecular Weight Proteins in a Controlled Manner over an Extended Time

In Situ Forming iEDDA Hydrogels with Tunable Gelation Time Release High-Molecular Weight Proteins in a Controlled Manner over an Extended Time

Hyaluronic Acid Hydrogels Crosslinked in Physiological Conditions: Synthesis and Biomedical Applications

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

Contact Info

Product

Resources

About