Gelatin Methacrylate Hydrogels as Biomimetic Three-Dimensional Matrixes for Modeling Breast Cancer Invasion and Chemoresponse in Vitro

Arya, Anuradha D; Hallur, Pavan M.; Karkisaval, Abhijith G; Gudipati, Aditi; Rajendiran, Satheesh; Dhavale, Vaibhav; Ramachandran, Balaji; Jayaprakash, Aravindakshan; Gundiah, Namrata; Chaubey, Aditya

doi:10.1021/acsami.6b06309

Cited by 72 publications

(71 citation statements)

References 86 publications

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“…From the SEM images, it can be seen that 2% w/v alginate exhibits more oblong and larger pores, compared with the smaller honeycomb‐like pores in 7.5% w/v GelMA. These results are in accordance with previous work from Yao et al, Arya et al, and Athirasala et al, who demonstrated similar alginate and GelMA hydrogel microstructures. SEM of the cross‐sectional area of a hydrogel obtained from combining the two polymers shows clear differences in architecture and porosity.…”

Section: Resultssupporting

confidence: 94%

Development of a Coaxial 3D Printing Platform for Biofabrication of Implantable Islet‐Containing Constructs

Liu

Carter

Renes

et al. 2019

Adv Healthcare Materials

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Over the last two decades, pancreatic islet transplantations have become a promising treatment for Type I diabetes. However, although providing a consistent and sustained exogenous insulin supply, there are a number of limitations hindering the widespread application of this approach. These include the lack of sufficient vasculature and allogeneic immune attacks after transplantation, which both contribute to poor cell survival rates. Here, these issues are addressed using a biofabrication approach. An alginate/gelatin‐based bioink formulation is optimized for islet and islet‐related cell encapsulation and 3D printing. In addition, a custom‐designed coaxial printer is developed for 3D printing of multicellular islet‐containing constructs. In this work, the ability to fabricate 3D constructs with precise control over the distribution of multiple cell types is demonstrated. In addition, it is shown that the viability of pancreatic islets is well maintained after the 3D printing process. Taken together, these results represent the first step toward an improved vehicle for islet transplantation and a potential novel strategy to treat Type I diabetes.

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Section: Resultssupporting

confidence: 94%

Development of a Coaxial 3D Printing Platform for Biofabrication of Implantable Islet‐Containing Constructs

Liu

Carter

Renes

et al. 2019

Adv Healthcare Materials

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“…For instance, Kaemmerer et al utilized photocrosslinkable gelatin methacrylamide (GelMA) hydrogel to study the growth of ovarian cancer cells [62]. GelMA hydrogel has been demonstrated to be advantageous for tissue engineering and 3D culture of numerous cell types due to the high concentration of matrix metalloproteinase-(MMP) sensitive degradation sites [63][64][65][66][67].…”

Section: D Microengineered Models To Study Tumor Initiation and Growthmentioning

confidence: 99%

“…However, a potential drawback of traditional photocrosslinking techniques is the exposure of the cells to UV light, which could lead to cytotoxicity and/or mutagenesis. Despite this drawback, many studies have confirmed physiologically relevant cell behavior when embedded within GelMA hydrogel [62,64,67].…”

Section: D Microengineered Models To Study Tumor Initiation and Growthmentioning

confidence: 99%

Advanced biomaterials and microengineering technologies to recapitulate the stepwise process of cancer metastasis

et al. 2017

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Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions.

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“…Hence, there is a need to develop a 3D matrix which could be used to form spheroids inside the matrix and which can serve as a model for screening of new pharmacological compounds (Hoarau‐Véchot et al, ). There are studies where hydrogels have been used to develop spheroids for ovarian cancer (Kaemmerer et al, ) and breast cancer (Arya et al, ). However, very few studies have been reported for the formation of spheroids in cryogel based matrices (Bäcker et al, ; Göppert et al, ; Kumari, Karande, & Kumar, ; Lee et al, ; Sarkar & Kumar, ).…”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional cryogel matrix for spheroid formation and anti‐cancer drug screening

Singh

Tayalia

2019

J Biomedical Materials Res

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Spheroid-based systems have been developed as alternatives to two-dimensional (2D) monolayer cultures for understanding 3D cell behavior and conducting in vitro drug screening tests. However, spheroids are easily disrupted while handling and do not mimic the presence of extracellular matrix (ECM) components. To address that, we have developed a cost-effective, polyethylene glycol diacrylate (PEGDA), and gelatin methacryloyl (GELMA) based semi-synthetic cryogel matrix system, which can be used to grow spheroids and conduct studies while providing architectural support and mimicking in vivo ECM components. These matrices are macroporous and support formation of tumor-like spheroids of breast tumor epithelial (MCF-7) cells in the absence of additional growth factors otherwise required for spheroid formation. Difference in morphology of cells as a function of matrix composition and increase in size and number of spheroids as a function of time was observed. Spheroids grown in cryogel matrices showed more drug resistance than their 2D counterparts, which can partially be explained by the epithelial to mesenchymal transition (EMT) observed in spheroids. We believe that spheroids formed through these PEGDA-GELMA cryogel matrices better represent in vivo pathological conditions and can help develop costeffective in vitro assays for screening new pharmacological drug candidates and performing cell mechanistic studies. K E Y W O R D S 3D cell culture, breast cancer cells, cryogels or scaffolds, polyethylene glycol diacrylate, gelatin methacryloyl, spheroids PEG (molecular weight 4,000 Mw), anhydrous dichloromethane (DCM), anhydrous magnesium sulfate (MgSO 4 ), potassium carbonate (K 2 CO 3 ), diethyl ether, and toluene were purchased from Merck (India). Acryloyl chloride and methacrylic anhydride were purchased from Alfa Aesar. 2-Hydroxy-4 0 -(2-hydroxyethoxy)-2-methylpropiophenone and Paclitaxel were purchased from Sigma Aldrich, triethylamine (TEA), tetramethylethylenediamine (TEMED), and dialysis tubing (12 kDa MWCO) were purchased from HiMedia lab (India) and ammonium persulfate (APS) was purchased from Sisco Research Laboratories (SRL) India. Gelatin was a gift from Nitta Gelatin, India and Calcein-AM, DAPI, Phalloidin, Propidium Iodide, and trizol were purchased from Invitrogen. Dulbecco's Phosphate Buffer Saline (PBS), Dulbecco's Modified Eagle's Medium (DMEM), fetal bovine serum (FBS), and the antibiotic-antimycotic solution were purchased from HiMedia, India. EMT antibody sampler kit and Ki-67 antibody were purchased from Cell Signaling Technology and Brilliant II SYBR Green qPCR Master Mix and cDNA synthesis kit were purchased from Agilent Technologies and growth factor reduced Matrigel was purchased from BD Corning. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and bovine serum albumin (BSA) was purchased from Himedia Lab (India). | Cryogel preparationPEGDA and GELMA were synthesized and characterized as reported earlier in our previous work (Shrimali et al., 2018). Briefly, PEGDA was synthe...

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Gelatin Methacrylate Hydrogels as Biomimetic Three-Dimensional Matrixes for Modeling Breast Cancer Invasion and Chemoresponse in Vitro

Cited by 72 publications

References 86 publications

Development of a Coaxial 3D Printing Platform for Biofabrication of Implantable Islet‐Containing Constructs

Development of a Coaxial 3D Printing Platform for Biofabrication of Implantable Islet‐Containing Constructs

Advanced biomaterials and microengineering technologies to recapitulate the stepwise process of cancer metastasis

Three‐dimensional cryogel matrix for spheroid formation and anti‐cancer drug screening

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