Fast photocurable thiol-ene elastomers with tunable biodegradability, mechanical and surface properties enhance myoblast differentiation and contractile function

Mohamed, Mohamed Alaa; Shahini, Aref; Rajabian, Nika; Caserto, Julia S.; El-Sokkary, Ahmed M.A.; Akl, Magda A.; Andreadis, Stelios T.; Cheng, Chong

doi:10.1016/j.bioactmat.2020.12.022

Cited by 12 publications

(11 citation statements)

References 97 publications

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“…Conventional fluorescence imaging does not provide sufficient structural details, instead, leads to more blurry microscopic images (Fig. S1) [ 33 , 53 , 54 ]. However, the visualization of individual filaments or filament bundles is crucial to obtain reliable data regarding sarcomere organization.…”

Section: Discussionmentioning

confidence: 99%

Monitoring the maturation of the sarcomere network: a super-resolution microscopy-based approach

Skorska

Johann

Chabanovska

et al. 2022

Cell. Mol. Life Sci.

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The in vitro generation of human cardiomyocytes derived from induced pluripotent stem cells (iPSC) is of great importance for cardiac disease modeling, drug-testing applications and for regenerative medicine. Despite the development of various cultivation strategies, a sufficiently high degree of maturation is still a decisive limiting factor for the successful application of these cardiac cells. The maturation process includes, among others, the proper formation of sarcomere structures, mediating the contraction of cardiomyocytes. To precisely monitor the maturation of the contractile machinery, we have established an imaging-based strategy that allows quantitative evaluation of important parameters, defining the quality of the sarcomere network. iPSC-derived cardiomyocytes were subjected to different culture conditions to improve sarcomere formation, including prolonged cultivation time and micro patterned surfaces. Fluorescent images of α-actinin were acquired using super-resolution microscopy. Subsequently, we determined cell morphology, sarcomere density, filament alignment, z-Disc thickness and sarcomere length of iPSC-derived cardiomyocytes. Cells from adult and neonatal heart tissue served as control. Our image analysis revealed a profound effect on sarcomere content and filament orientation when iPSC-derived cardiomyocytes were cultured on structured, line-shaped surfaces. Similarly, prolonged cultivation time had a beneficial effect on the structural maturation, leading to a more adult-like phenotype. Automatic evaluation of the sarcomere filaments by machine learning validated our data. Moreover, we successfully transferred this approach to skeletal muscle cells, showing an improved sarcomere formation cells over different differentiation periods. Overall, our image-based workflow can be used as a straight-forward tool to quantitatively estimate the structural maturation of contractile cells. As such, it can support the establishment of novel differentiation protocols to enhance sarcomere formation and maturity.

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Section: Discussionmentioning

confidence: 99%

Monitoring the maturation of the sarcomere network: a super-resolution microscopy-based approach

Skorska

Johann

Chabanovska

et al. 2022

Cell. Mol. Life Sci.

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“…Further crosslinking of the pendant olefin groups using pH-sensitive 1,4-butanediol bis(3-mercaptopropionate) could stabilize the structure and tune the release behavior of DOX. Thiol-ene crosslinking was selected because of the fast reaction kinetics, without generating toxic by-products [ 52 ]. By varying the crosslinking density through changing the [SH]/[ENE] percent (5, 10, 20 mol%), a series of CMs were obtained.…”

Section: Discussionmentioning

confidence: 99%

Well-Defined pH-Sensitive Self-Assembled Triblock Copolymer-Based Crosslinked Micelles for Efficient Cancer Chemotherapy

et al. 2022

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Delivery of chemotherapeutics to cancer cells using polymeric micelles is a promising strategy for cancer treatment. However, limited stability of micelles, premature drug release and off-target effect are the major obstacles that restrict the utilization of polymeric micelles as effective drug delivery systems. In this work, we addressed these issues through the innovative design of targeted pH-sensitive crosslinked polymeric micelles for chemotherapeutic delivery. A well-defined triblock copolymer, poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate)-b-poly(butyl acrylate) (PEG-b-PHEMA-b-PBA), was synthesized by living radical polymerization, and then modified by using 4-pentenoic anhydride to incorporate pendant crosslinkable alkene groups in the middle block. The resulting copolymer underwent self-assembly in aqueous solution to form non-crosslinked micelles (NCMs). Subsequently, intramicellar thiol–ene crosslinking was performed by using 1,4-butanediol bis(3-mercaptopropionate) to give crosslinked micelles (CMs) with pH-sensitive crosslinks. The targeted CM (cRGD-DOX10-CM5) was readily prepared by using tumor-targeting ligand cyclo(Arg-Gly-Asp-D-Phe-Cys) (cRGD) together with the 1,4-butanediol bis(3-mercaptopropionate) during the crosslinking step. The study of cumulative DOX release revealed the pH-sensitive feature of drug release from these CMs. An in vitro MTT assay revealed that NCMs and CMs are biocompatible with MCF 10A cells, and the samples exhibited significant therapeutic efficiency as compared to free DOX. Cellular uptake studies confirmed higher uptake of cRGD-DOX10-CM5 by MCF 10A cancer cells via cRGD-receptor-mediated endocytosis as compared to the corresponding analogues without cRGD. These results indicate that such pH-responsive crosslinked PEG-b-PHEMA-b-PBA-based micelles are therapeutically effective against cancer cells and hold remarkable promise to act as smart drug delivery systems for cancer therapy.

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“…42,52 In order to develop scaffolds that can withstand recurring dynamic loads and also provide suitable conditions for cell attachment, proliferation, and differentiation, it is essential to design degradable elastomers with mechanical and surface properties that mimic soft tissues. 53 As a result, PGS-co-PEG copolymers are well suited to such applications.…”

Section: Biomaterials Science Accepted Manuscriptmentioning

confidence: 99%

Elastomeric, bioadhesive and pH-responsive amphiphilic copolymers based on direct crosslinking of poly(glycerol sebacate)-co-polyethylene glycol

et al. 2022

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Fast photocurable thiol-ene elastomers with tunable biodegradability, mechanical and surface properties enhance myoblast differentiation and contractile function

Cited by 12 publications

References 97 publications

Monitoring the maturation of the sarcomere network: a super-resolution microscopy-based approach

Monitoring the maturation of the sarcomere network: a super-resolution microscopy-based approach

Well-Defined pH-Sensitive Self-Assembled Triblock Copolymer-Based Crosslinked Micelles for Efficient Cancer Chemotherapy

Elastomeric, bioadhesive and pH-responsive amphiphilic copolymers based on direct crosslinking of poly(glycerol sebacate)-co-polyethylene glycol

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