Tunable Engineering of Heparinized Injectable Hydrogels for Affinity‐Based Sustained Delivery of Bioactive Factors

Abstract

Here, the design of an in situ‐forming injectable hydrogel is reported based on pH‐ and temperature‐responsive copolymers finely engineered with heparin for the sustained delivery of bioactive factors. In order to develop such heparinized injectable hydrogels, pH‐ and temperature‐responsive copolymers based on poly(ethylene glycol) and poly(urethane sulfamethazine) (PEG‐PUSSM) are synthesized and acrylated, and subsequently coupled with thiolated heparin through Michael‐addition reaction. The content of heparin in the bioconjugates (Hep‐PUSSM) is finely tuned to control the release of heparin‐binding bioactive factors. The free‐flowing bioconjugate sols at room temperature transform to stable viscoelastic gel in physiological conditions, indicating that heparin modification does not affect the sol–gel transition. The subcutaneous administration of bioconjugate sols to the dorsal‐region of Sprague‐Dawley rats forms a hydrogel depot and shows controlled degradation. The bioconjugates effectively bind with bioactive factors (VEGF) through simple mixing, and the release is controlled over a period of 4 weeks without an initial burst. As a result, the implantation of VEGF‐loaded bioconjugate gel induces angiogenesis throughout the hydrogel network. The tunable engineering of the injectable hydrogel by heparinization with independent controllable physical properties sustains the release of bioactive factors, indicating that it may be a promising platform for the delivery of bioactive factors.

Biobased polyurethanes for biomedical applications

“…For areas where degradation should be tunable like drug delivery, PUs are usually developed in forms of electrospun networks [ 160 , 161 ], hydrogels [ 162 , 163 ], membranes [ 164 ] or nanocarriers like micelles [ 165 ] when quick drug release is needed. As PUs degradation process is mainly determined by the SS, degradation rates for tailored drug release time are obtained by varying the type and amount of polyols undergoing hydrolytic and enzymatic degradations such as polyesters-based polyols, to hydrophilic polyols undergoing water uptake and oxidative degradation like polyether-based polyols [ 166 , 167 ].…”

Gene Regulations upon Hydrogel-Mediated Drug Delivery Systems in Skin Cancers—An Overview

“…For instance, highly porous structures permit more adherence and entrap the therapeutic agents in it, and the release of therapeutic agents can be controlled by regulating its porous structure [ 98 , 99 , 100 ]. These high swelling properties of biocarriers have a comparable degree of elasticity to natural tissues, and can undergo gel–solid phase transitions in response to various types of stimuli such as temperature, light, pressure, electric field, magnetic field, ionic strength and pH [ 101 , 102 , 103 ]. The natural polymers have reached a considerable significance in drug delivery applications, due to their characteristics such as biocompatibility, biodegradability, bifunctionality, biochemical stability, improved drug solubility, controlled drug release, cost effectiveness and nontoxicity [ 104 , 105 , 106 , 107 ].…”

Recent developments of temperature‐responsive polymers for ophthalmic applications

“…Lee et al has reviewed temperature‐ and pH‐responsive block copolymer hydrogels which are the most popular physical and chemical stimuli, respectively 48,49 . The group has gone on to publish extensively on dual‐stimuli‐responsive hydrogels for biomedical applications 50–58 . Very recently, our group has also published several reviews, which looked at different aspects of thermogels.…”

“…48,49 The group has gone on to publish extensively on dual-stimuliresponsive hydrogels for biomedical applications. [50][51][52][53][54][55][56][57][58] Very recently, our group has also published several reviews, which looked at different aspects of thermogels. Zhang et al discussed important thermogelling properties such as the lower critical solution temperature (LCST), micellar configuration and gelling mechanism.…”