Injectable thermogel for 3D culture of stem cells

Patel, Madhumita; Lee, Hyun Jung; Park, Sohee; Kim, Yelin; Jeong, Byeongmoon

doi:10.1016/j.biomaterials.2018.01.001

Cited by 93 publications

(87 citation statements)

References 163 publications

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“…Over the past two decades, injectable in situ‐forming hydrogels have received growing attention in virtue of the unique superiority of minimal invasion application. [ 6 ] In particular, some amphiphilic block copolymers of hydrophobic and biodegradable polyesters, like poly( d , l ‐lactide‐ co ‐glycolide) (PLGA), and hydrophilic poly(ethylene glycol) (PEG) can be dissolved in water at ambient temperature, and subsequently the free‐flowing sols can spontaneously turn into standing in situ gels when exposed to physiological temperature. [ 7 ] The temperature‐triggered physical gelation avoids the side effects induced by the chemical reaction.…”

Section: Introductionmentioning

confidence: 99%

Visualizing the In Vivo Evolution of an Injectable and Thermosensitive Hydrogel Using Tri‐Modal Bioimaging

Chen

Zhang

et al. 2020

Small Methods

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Degradability of biomaterials brings many opportunities as well as great challenges to their clinical applications. However, reports of systematic in vivo biodegradation are rather limited due to lack of adequate methodology for real‐time observations. Herein, a tri‐modal bioimaging technique is developed, enabling real time monitoring of biodegradation of synthetic polymers in vivo. The demonstrated material is a successful preclinical poly(lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(lactic acid‐co‐glycolic acid) thermosensitive hydrogel that undergoes a spontaneous sol–gel transition upon heating. A macromolecular fluorescence probe and a contrast agent of magnetic resonance imaging (MRI) are designed and synthesized. After subcutaneous injection of the hydrogel containing the two probes into mice, the degradation behaviors of the material are longitudinally and noninvasively tracked via the collaborative application of ultrasound, fluorescence, and MRI. Integrating the noninvasive imaging with the traditional anatomic observations, a three‐stage degradation mechanism of such a hydrogel is proposed for the first time. Also, the dissolved polymers and degradation products in the body are mainly eliminated via liver, gallbladder, and spleen. This work has great value for promoting the future clinical application of these kind of promising hydrogels. Meanwhile, this technological platform provides beneficial inspiration and methodology to investigate in vivo fate of biomaterials.

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Section: Introductionmentioning

confidence: 99%

Visualizing the In Vivo Evolution of an Injectable and Thermosensitive Hydrogel Using Tri‐Modal Bioimaging

Chen

Zhang

et al. 2020

Small Methods

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“…Hydrolysis of phosphate ester bonds of MAEP is accelerated in the presence of alkaline phosphatase, which is upregulated in bone regenerative sites. [110,130] The thermal-responsive ability of polymers can also be used to induce porosity in the hydrogel matrix. [114] High and low MAEP were selected for in vitro and in vivo characterization to evaluate their potential to encapsulate mesenchymal stem cells (MSCs) and regenerate bone tissue.…”

Section: Temperature-responsive Cell Encapsulation Systemsmentioning

confidence: 99%

“…IV) Magnetic directed assembly of microgels produced by micromolding. [110] On the other hand, instead of functionalizing the encapsulation matrix with biomolecules, Matrigel has been used to encapsulate cells since it contains a plethora of basement membrane components of collagens, laminin, entactin, and heparan sulfate, proteoglycan, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor, nerve growth factor, TGF-β, among other biochemical components not fully identified. Scale bar is 500 µm.…”

Section: Temperature-responsive Cell Encapsulation Systemsmentioning

confidence: 99%

Design Principles and Multifunctionality in Cell Encapsulation Systems for Tissue Regeneration

Correia

Reis

Mano

2018

Adv Healthcare Materials

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Cell encapsulation systems are being increasingly applied as multifunctional strategies to regenerate tissues. Lessons afforded with encapsulation systems aiming to treat endocrine diseases seem to be highly valuable for the tissue engineering and regenerative medicine (TERM) systems of today, in which tissue regeneration and biomaterial integration are key components. Innumerous multifunctional systems for cell compartmentalization are being proposed to meet the specific needs required in the TERM field. Herein is reviewed the variable geometries proposed to produce cell encapsulation strategies toward tissue regeneration, including spherical and fiber-shaped systems, and other complex shapes and arrangements that better mimic the highly hierarchical organization of native tissues. The application of such principles in the TERM field brings new possibilities for the development of highly complex systems, which holds tremendous promise for tissue regeneration. The complex systems aim to recreate adequate environmental signals found in native tissue (in particular during the regenerative process) to control the cellular outcome, and conferring multifunctional properties, namely the incorporation of bioactive molecules and the ability to create smart and adaptative systems in response to different stimuli. The new multifunctional properties of such systems that are being employed to fulfill the requirements of the TERM field are also discussed.

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“…Here, we report thermogelling PEG–PCL–PEG triblock copolymers that can be degraded by ROS. Thermogelling systems have been investigated for drug delivery, 3D cell culture, and prevention of postoperative tissue adhesion . The degradation of a middle oxalate functional group leads to PEG–PCL diblock copolymers that are expected to show different phase behavior and a corresponding reduction in gel duration.…”

Section: Introductionmentioning

confidence: 99%

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

Lee

Jeong

2019

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A reactive oxygen species (ROS)‐sensitive degradable polymer would be a promising material in designing a disease‐responsive system or accelerating degradation of polymers with slow hydrolysis kinetics. Here, a thermogelling poly(ethylene glycol)–polycaprolactone–poly(ethylene glycol) (PEG–PCL–PEG or EG12–CL20–EG12) triblock copolymer with an oxalate group at the middle of the polymer is reported. The polymers form micelles with an average size of 100 nm in water. Thermogelation is observed in a concentration range of 8.0−37.0 wt%. In particular, the aqueous PEG–PCL–PEG triblock copolymer solutions are in a gel state at 37 °C in a concentration range of 25.0–37.0 wt%, whereas the aqueous PEG–PCL diblock copolymer solutions are in a sol state in the same concentration range at 37 °C. Thus, the gel depot could dissolve out once degradation of the triblock copolymers occurs at the oxalate group as confirmed by the in vitro experiment. In vivo gel formation is confirmed by injecting an aqueous PEG–PCL–PEG solution (36.0 wt%) into the subcutaneous layer of rats. The gel completely disappears in 21 d. A model polypeptide drug (cyclosporine A) is released over 21 d from the in situ formed gel. The micelle‐based thermogel of PEG–PCL–PEG with ROS‐triggering degradability is a promising injectable material for biomedical applications.

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Injectable thermogel for 3D culture of stem cells

Cited by 93 publications

References 163 publications

Visualizing the In Vivo Evolution of an Injectable and Thermosensitive Hydrogel Using Tri‐Modal Bioimaging

Visualizing the In Vivo Evolution of an Injectable and Thermosensitive Hydrogel Using Tri‐Modal Bioimaging

Design Principles and Multifunctionality in Cell Encapsulation Systems for Tissue Regeneration

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

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