Search Results (6)

Cancer stem cells (CSCs) are most likely the main cause of lung cancer formation, metastasis, drug resistance, and genetic heterogeneity. Three-dimensional (3D) ex vivo cell culture models can facilitate stemness improvement and CSC enrichment. Considering the critical role of extracellular matrix (ECM) on CSC properties, the present study developed a thermo-responsive hydrogel using the porcine decellularized lung for 3D cell culture, and the cell-laden hydrogel culturing model was used to explore the CSC characteristics and potential utilization in CSC-specific drug evaluation. Results showed that the lung dECM hydrogel (LEH) was composed of the main ECM components and displayed excellent cellular compatibility. In addition, lung cancer cells 3D cultured in LEH displayed the overexpression of metastasis-related genes and enhanced migration properties, as compared with those in two-dimensional (2D) conditions. Notably, the CSC features, including the expression level of stemness-associated genes, colony formation capability, drug resistance, and the proportion of cancer stem-like cells (CD133⁺), were also enhanced in 3D cells. Furthermore, the attenuation effect of epigallocatechin gallate (EGCG) on CSC properties in the 3D model was observed, confirming the potential practicability of the 3D culture on CSC-targeted drug screening. Overall, our results suggest that the fabricated LEH is an effective and facile platform for 3D cell culture and CSC-specific drug evaluation. Full article

Thermoresponsive sol–gel transition polymers are of significant interest because of their fascinating biomedical applications, including as drug reservoirs for drug delivery systems and scaffolds for tissue engineering. Although extensive research has been conducted on lower critical solution temperature (LCST)-type sol–gel transition polymers, there have been few reports on upper critical solution temperature (UCST)-type sol–gel transition polymers. In this study, we designed an ABA-type triblock copolymer composed of a poly(ethylene glycol) (PEG) block and zwitterionic polymer blocks that exhibit UCST-type thermoresponsive phase transitions. A sulfobetaine (SB) monomer with both ammonium and sulfonate (–SO₃) groups in its side chain or a sulfabetaine (SaB) monomer with both ammonium and sulfate (–OSO₃) groups in its side chain was polymerized from both ends of the PEG block via reversible addition–fragmentation chain-transfer (RAFT) polymerization to obtain PSB-PEG-PSB and PSaB-PEG-PSaB triblock copolymers, respectively. Although an aqueous solution containing the PSB-PEG-PSB triblock copolymer showed an increase in viscosity upon cooling, it did not undergo a sol-to-gel transition. In contrast, a sol-to-gel transition was observed when a phosphate-buffered saline containing PSaB-PEG-PSaB was cooled from 80 °C to 25 °C. The PSaB blocks with –OSO₃ groups exhibited a stronger dipole–dipole interaction than conventional SB with –SO₃ groups, leading to intermolecular association and the formation of a gel network composed of PSaB assemblies bridged with PEG. The fascinating UCST-type thermoresponsive sol–gel transition properties of the PSaB-PEG-PSaB triblock copolymer suggest that it can provide a useful platform for designing smart biomaterials, such as drug delivery reservoirs and cell culture scaffolds. Full article

Antheraea pernyi silk fibroin (ASF)-based nanofibers have wide potential for biomaterial applications due to superior biocompatibility. It is not clear whether the ASF-based nanofibers scaffold can be used as an in vitro cancer cell culture platform. In the current study, we fabricated novel ASF-based thermoresponsive hydrogel nanofibers by aqueous electrospinning for colon cancer (LoVo) cells culture. ASF was reacted with allyl glycidyl ether (AGE) for the preparation of allyl silk fibroin (ASF-AGE), which provided the possibility of copolymerization with allyl monomer. The investigation of ASF-AGE structure by ¹H NMR revealed that reactive allyl groups were successfully linked with ASF. ASF-based thermoresponsive hydrogel nanofibers (p (ASF-AGE-NIPAAm)) were successfully manufactured by aqueous electrospinning with the polymerization of ASF and N-isopropylacrylamide (NIPAAm). The p (ASF-AGE-NIPAAm) spinning solution showed good spinnability with the increase of polymerization time, and uniform nanofibers were formed at the polymerization time of 360 min. The obtained hydrogel nanofibers exhibited good thermoresponsive that the LCST was similar with PNIPAAm at about 32 °C, and good degradability in protease XIV PBS solution. In addition, the cytocompatibility of colon cancer (LoVo) cells cultured in hydrogel nanofibers was assessed. It was demonstrated that LoVo cells grown on hydrogel nanofibers showed improved cell adhesion, proliferation, and viability than those on hydrogel. The results suggest that the p (ASF-AGE-NIPAAm) hydrogel nanofibers have potential application in LoVo cells culture in vitro. This study demonstrates the feasibility of fabricating ASF-based nanofibers to culture LoVo cancer cells that can potentially be used as an in vitro cancer cell culture platform. Full article

Thermogels are also known as thermo-sensitive or thermo-responsive hydrogels and can undergo a sol–gel transition as the temperature increases. This thermogelling behavior is the result of combined action from multiscale thermo-responsive mechanisms. From micro to macro, these mechanisms can be attributed to LCST behavior, micellization, and micelle aggregation of thermogelling polymers. Due to its facile phase conversion properties, thermogels are injectable yet can form an in situ gel in the human body. Thermogels act as a useful platform biomaterial that operates at physiological body temperatures. The purpose of this review is to summarize the recent progress in thermogel research, including investigations on the thermogel gelation mechanism and its applications in drug delivery, 3D cell culture, and tissue engineering. The review also discusses emerging directions in the study of thermogels. Full article

Poly(N-isopropylacrylamide) (PNIPAAm) is a typical thermoresponsive polymer used widely and studied deeply in smart materials, which is attractive and valuable owing to its reversible and remote “on–off” behavior adjusted by temperature variation. PNIPAAm usually exhibits opposite solubility or wettability across lower critical solution temperature (LCST), and it is readily functionalized making it available in extensive applications. Cell culture is one of the most prospective and representative applications. Active attachment and spontaneous detachment of targeted cells are easily tunable by surface wettability changes and volume phase transitions of PNIPAAm modified substrates with respect to ambient temperature. The thermoresponsive culture platforms and matching thermal-liftoff method can effectively substitute for the traditional cell harvesting ways like enzymatic hydrolysis and mechanical scraping, and will improve the stable and high quality of recovered cells. Therefore, the establishment and detection on PNIPAAm based culture systems are of particular importance. This review covers the important developments and recommendations for future work of the preparation and characterization of temperature-responsive substrates based on PNIPAAm and analogues for cell culture applications. Full article

Temperature-triggered copolymers are proposed for a number of bio-applications but there is no ideal material platform, especially for injectable drug delivery. Options are needed for degradable biomaterials that not only respond to temperature but also easily accommodate linkage of active molecules. A first step toward realizing this goal is the design and synthesis of the novel materials reported herein. A multifunctional macromer, methacrylated hyperbranched polyglycerol (HPG-MA) with an average of one acrylate unit per copolymer, was synthesized and copolymerized with N-isopropylacrylamide (NIPAAm), hydroxyethyl methacrylate-polylactide (HEMAPLA) and acrylic acid (AAc). The potential to fully exploit the copolymers by modification of the multiple HPG hydroxyl groups will not be discussed here. Instead, this report focuses on the thermoresponsive, biocompatible, and degradation properties of the material. Poly(NIPAAm-co-HEMAPLA-co-AAc-co-HPG-MA) displayed increasing lower critical solution temperatures (LCST) as the HPG content increased over a range of macromer ratios. For the copolymer with the maximum HPG incorporation (17%), the LCST was ~30 °C. In addition, this sample showed no toxicity when human uterine fibroid cells were co-cultured with the copolymer for up to 72 h. This copolymer lost approximately 92% of its mass after 17 hours at 37 °C. Thus, the reported biomaterials offer attractive properties for the design of drug delivery systems where orthogonally triggered mechanisms of therapeutic release in relatively short time periods would be attractive. Full article