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Synthesis and biocompatibility of a biodegradable and functionalizable thermo-sensitive hydrogel.

ABSTRACT: Injectable thermal gels are a useful tool for drug delivery and tissue engineering. However, most thermal gels do not solidify rapidly at body temperature (37°C). We addressed this by synthesizing a thermo-sensitive, rapidly biodegrading hydrogel. Our hydrogel, poly(ethylene glycol)-co-poly(propanol serinate hexamethylene urethane) (EPSHU), is an ABA block copolymer comprising A, methoxy poly ethylene glycol group and B, poly (propanol L-serinate hexamethylene urethane). EPSHU was characterized by gel permeation chromatography for molecular weight and (1)H NMR and Fourier transformed infrared for structure. Rheological studies measured the phase transition temperature. In vitro degradation in cholesterol esterase and in Dulbecco's phosphate buffered saline (DPBS) was tracked using the average molecular weight measured by gel permeation chromatography. LIVE/DEAD and resazurin reduction assays performed on NIH 3T3 fibroblasts exposed to EPSHU extracts demonstrated no cytotoxicity. Subcutaneous implantation into BALB/cJ mice indicated good biocompatibility in vivo. The biodegradability and biocompatibility of EPSHU together make it a promising candidate for drug delivery applications that demand carrier gel degradation within months.

SUBMITTER: Sinha MK

PROVIDER: S-EPMC4669011 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Synthesis and biocompatibility of a biodegradable and functionalizable thermo-sensitive hydrogel.

Sinha Mantosh K MK Gao Jin J Stowell Chelsea E T CE Wang Yadong Y

Regenerative biomaterials 20150820 3

Injectable thermal gels are a useful tool for drug delivery and tissue engineering. However, most thermal gels do not solidify rapidly at body temperature (37°C). We addressed this by synthesizing a thermo-sensitive, rapidly biodegrading hydrogel. Our hydrogel, poly(ethylene glycol)-co-poly(propanol serinate hexamethylene urethane) (EPSHU), is an ABA block copolymer comprising A, methoxy poly ethylene glycol group and B, poly (propanol L-serinate hexamethylene urethane). EPSHU was characterized ...[more]

PMID: 26814023

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Project description:Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell-cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.

Dataset Information

Synthesis and biocompatibility of a biodegradable and functionalizable thermo-sensitive hydrogel.

Publications

Synthesis and biocompatibility of a biodegradable and functionalizable thermo-sensitive hydrogel.

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