Patterned PHEMA Films Synthesized by Redox Polymerization for Multicellular Spheroid Generation

Yun, Yifan; Guan, Ying; Zhang, Yongjun

doi:10.1021/acs.iecr.9b01517

Cited by 7 publications

(21 citation statements)

References 46 publications

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“…[ 7,18 ] Herein, we used patterned PHEMA hydrogel films to generate ADSC spheroids. [ 20–22 ] As shown in Figure S1A, Supporting Information, first flat hydrogel films were synthesized in situ in the wells of 12‐well plates by photo‐curing of a pre‐gel solution containing HEMA monomer, photo‐initiator Darocur 1173, cross‐linker ethylene glycol dimethacrylate (EGDMA), and linear PHEMA. The hydrogel films were then patterned by simple adding water to swell them.…”

Section: Resultsmentioning

confidence: 99%

“…[30] To prepare ADSC spheroids, the cell suspension was added into the wells modified with patterned PHEMA films (Figure S1D, Supporting Information). [20][21][22] The cells settled down onto the gel surface and gathered to the center of the hexagonal patterns. Because of the non-adhesive nature of the PHEMA hydrogel film, the cells did not attach onto the gel surface.…”

Section: Massive Production Of Uniform-sized Adsc Multicellular Spher...mentioning

confidence: 99%

“…The PHEMA films were synthesized in situ in the wells of commercial cell culture plates and spontaneously patterned by swelling in water without using any template, mask, or special facilities. [20][21][22][23] Guided by these uniform microstructures, uniform-sized multicellular spheroids of adipose-derived stromal cells (ADSCs) were generated successfully. In addition, this method allows for high-throughput production of the spheroids and fine control on the spheroid sizes.…”

Section: Introductionmentioning

confidence: 99%

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Uniformly Sized Stem Cell Spheroids for Treatment of Hind Limb Ischemia: Size Effect

Cui

Luo

Wang

et al. 2022

Adv Materials Inter

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Spheroid‐based cell delivery has been demonstrated as an effective strategy in stem cell therapy of critical limb ischemia. However, massive generation of uniform‐sized spheroids still remains a big challenge. In addition, how spheroid size influences its therapeutic efficacy remains an open question. Herein, patterned poly(2‐hydroxyethyl methacrylate) hydrogel films synthesized in situ in cell culture plates are used to generate adipose‐derived stromal cell (ADSC) spheroids. This method not only allows for the production of uniform‐sized spheroids but also large‐scale production (≈60 000 spheroids per plate). Using this method, monodisperse ADSC spheroids with three different sizes are generated to study spheroid size effect in ischemia treatment. It is found that different size spheroids exhibit different behaviors in extracellular matrix (ECM) expression and paracrine secretion. Larger spheroids express more ECM proteins. Paracrine secretion of hypoxia‐induced survival factors, anti‐apoptotic and angiogenic factors is enhanced to a larger degree in larger spheroids. Finally, using a mouse model of hind limb ischemia, it is demonstrated that the therapeutic efficacy of the spheroids increases with increasing spheroid size. The improved therapeutic efficacy is attributed to enhanced survival and paracrine secretion of larger spheroids, which is attributed to the higher degree of hypoxic environment of these spheroids.

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Section: Resultsmentioning

confidence: 99%

Section: Massive Production Of Uniform-sized Adsc Multicellular Spher...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Uniformly Sized Stem Cell Spheroids for Treatment of Hind Limb Ischemia: Size Effect

Cui

Luo

Wang

et al. 2022

Adv Materials Inter

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“…To simplify the synthesis, a one-step UV curing method was later developed by adding linear PHEMA into the prepolymer solution . The UV irradiation step was further omitted by using redox polymerization, instead of photopolymerization, in the synthesis of PHEMA films . Although the PHEMA films were successfully synthesized and patterned, it was inevitable that some low molecular weight initiator, cross-linker, and monomer, which are potentially cytotoxic, − would remain in the resulting films and lower the biocompatibility of the films.…”

Section: Introductionmentioning

confidence: 99%

“…Although the PHEMA films were successfully synthesized and patterned, it was inevitable that some low molecular weight initiator, cross-linker, and monomer, which are potentially cytotoxic, − would remain in the resulting films and lower the biocompatibility of the films. For this reason, the films must be extensively washed to remove these low molecular weight compounds before cell seeding. ,, …”

Section: Introductionmentioning

confidence: 99%

Diels–Alder Cross-Linked, Washing-Free Hydrogel Films with Ordered Wrinkling Patterns for Multicellular Spheroid Generation

et al. 2021

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Three-dimensional (3D) multicellular spheroids are a new generation in vitro cell model, however, their applications are severely limited by difficulties in their generation. Here patterned poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel films were synthesized for their generation. Instead of polymerization of HEMA monomers in the presence of a cross-linker, here the PHEMA films were synthesized by cross-linking furan-functionalized linear PHEMA, PHEMA-furan, and maleimide-functionalized linear PHEMA, PHEMA-mal, via Diels−Alder (DA) reaction between furan and maleimide groups. A thermal treatment temperature of 75 °C was chosen for the cross-linking reaction. The occurrence of DA reaction was confirmed by IR spectra. Using this method, cross-linked PHEMA films with smooth surface were successfully synthesized in situ in the well of cell culture plates. The films were then patterned by simply adding water to swell them. Highly ordered, honeycomb-like wrinkling patterns were successfully obtained by adjusting the furan and maleimide contents in the precursor linear polymers. The patterned hydrogel films were used to generate multicellular spheroids. Guided by the patterns, 3D spheroids with narrow size distribution, tunable size, and high cell viability were successfully obtained. The patterned PHEMA films reported here exhibited a lot of advantages. The patterning method was quite simple and required no template or special equipment. They were synthesized in situ in commercial cell culture plates. Particularly, thanks to the clean nature of the DA reaction, no low molecular weight monomer, cross-linker, initiator, or catalyst, which were potentially cytotoxic, was involved in the film synthesis, and no byproduct was produced and left in the film. The resulting films presented a high biocompatibility, allowing the avoidance of the tedious washing step. The films synthesized here were expected to have high potential for massive production of well-defined multicellular spheroids.

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Wrinkled Interfaces: Taking Advantage of Anisotropic Wrinkling to Periodically Pattern Polymer Surfaces

et al. 2023

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Periodically patterned surfaces can cause special surface properties and are employed as functional building blocks in many devices, yet remaining challenges in fabrication. Advancements in fabricating structured polymer surfaces for obtaining periodic patterns are accomplished by adopting "top-down" strategies based on self-assembly or physico-chemical growth of atoms, molecules, or particles or "bottom-up" strategies ranging from traditional micromolding (embossing) or micro/nanoimprinting to novel laser-induced periodic surface structure, soft lithography, or direct laser interference patterning among others. Thus, technological advances directly promote higher resolution capabilities. Contrasted with the above techniques requiring highly sophisticated tools, surface instabilities taking advantage of the intrinsic properties of polymers induce surface wrinkling in order to fabricate periodically oriented wrinkled patterns. Such abundant and elaborate patterns are obtained as a result of self-organizing processes that are rather difficult if not impossible to fabricate through conventional patterning techniques. Focusing on oriented wrinkles, this review thoroughly describes the formation mechanisms and fabrication approaches for oriented wrinkles, as well as their fine-tuning in the wavelength, amplitude, and orientation control. Finally, the major applications in which oriented wrinkled interfaces are already in use or may be prospective in the near future are overviewed.

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Patterned PHEMA Films Synthesized by Redox Polymerization for Multicellular Spheroid Generation

Cited by 7 publications

References 46 publications

Uniformly Sized Stem Cell Spheroids for Treatment of Hind Limb Ischemia: Size Effect

Uniformly Sized Stem Cell Spheroids for Treatment of Hind Limb Ischemia: Size Effect

Diels–Alder Cross-Linked, Washing-Free Hydrogel Films with Ordered Wrinkling Patterns for Multicellular Spheroid Generation

Wrinkled Interfaces: Taking Advantage of Anisotropic Wrinkling to Periodically Pattern Polymer Surfaces

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