Thiol Click Modification of Cyclic Disulfide Containing Biodegradable Polyurethane Urea Elastomers

Abstract

Although the thiol click reaction is an attractive tool for postpolymerization modification of thiolmers, thiol groups are easily oxidized, limiting the potential for covalent immobilization of bioactive molecules. In this study, a series of biodegradable polyurethane elastomers incorporating stable cyclic disulfide groups was developed and characterized. These poly(ester urethane)urea (PEUU-SS) polymers were based on polycaprolactone diol (PCL), oxidized dl-dithiothreitol (O-DTT), lysine diisocyanate (LDI), or butyl diisocyanate (BDI), with chain extension by putrescine. The ratio of O-DTT:PCL was altered to investigate different levels of potential functionalization. PEG acrylate was employed to study the mechanism and availability of both bulk and surface click modification of PEUU-SS polymers. All synthesized PEUU-SS polymers were elastic with breaking strengths of 38-45 MPa, while the PEUU-SS(LDI) polymers were more amorphous, possessing lower moduli and relatively small permanent deformations versus PEUU-SS(BDI) polymers. Variable bulk click modification of PEUU-SS(LDI) polymers was achieved by controlling the amount of reduction reagent, and rapid reaction rates occurred using a one-pot, two-step process. Likewise, surface click reaction could be carried out quickly under mild, aqueous conditions. Furthermore, a maleimide-modified affinity peptide (TPS) was successfully clicked on the surface of an electrospun PEUU-SS(BDI) fibrous sheet, which improved endothelial progenitor cell adhesion versus corresponding unmodified films. The cyclic disulfide containing biodegradable polyurethanes described provide an option for cardiovascular and other soft tissue regenerative medicine applications where a temporary, elastic scaffold with designed biofunctionality from a relatively simple click chemistry approach is desired.

Synthesis of polyurethanes with pendant azide groups attached on the soft segments and the surface modification with mPEG by click chemistry for antifouling applications

“…More recently, alkynyl, azide or cyclic disulde groups were introduced into hard/so segments of polyurethanes for further functionalization using click chemistry. [13][14][15][16] Numerous laboratories prepared bioactive modication of biodegradable polyurethane which pendent alkynyl on hard segment and azide-ended peptide were linked to form a 1,2,3-triazole with covalent bonding by click reaction. [17][18][19][20] Taking into account the surface self-enrichment of sosegments of PUs as a result of their higher mobility than hard-segments, polyurethane with pendant azide groups on the so segment (PU-GAP) was prepared rstly in this study to further increase the content of azide groups and improve their surface enrichment.…”

Preparation and evaluation of poly(ester-urethane) urea/gelatin nanofibers based on different crosslinking strategies for potential applications in vascular tissue engineering

“…28 The cyclical mechanical properties reect the sustainability of these nanobrous scaffolds in the long term. 12,30,31 The cyclical tensile test results are shown in Fig. 5.…”

“…10 Poly(ester-urethane) urea (PEUU) is one critical member of the biodegradable polyurethane family due to its cytocompatibility, non-toxic degradation products, and ability to be processed into scaffolds via various techniques. [11][12][13] This material, with different types of so and hard segments, has been used for tissue-engineering scaffolds and is expected to be an excellent alternative due to its tunable mechanical properties, biodegradability, biocompatibility, and ability to be processed into scaffolds via various techniques. 14,15 Gelatin has ubiquitously been electrospun in combination with synthetic polymers, mostly by blending 7 or coating.…”

Crosslinked, biodegradable polyurethanes for precision‐porous biomaterials: Synthesis and properties

“…The in vivo biostability of such polymers is controversial with particular concerns that if they break down, they will lose their mechanical properties and also their products of degradation may be toxic. Although biostable PUs are still needed for medical devices, there is an increasing interest in nontoxic, biodegradable PUs useful for tissue engineering scaffolds . To address this interest, one can take advantage of the compositional flexibility of urethane polymers allowing a wide range of chemistries that can be designed to break down to nontoxic products.…”

“…Although biostable PUs are still needed for medical devices, there is an increasing interest in nontoxic, biodegradable PUs useful for tissue engineering scaffolds. [4][5][6][7] To address this interest, one can take advantage of the compositional flexibility of urethane polymers allowing a wide range of chemistries that can be designed to break down to nontoxic products.…”