Collagen Type I–Gelatin Methacryloyl Composites: Mimicking the Tumor Microenvironment

Abstract

Therapeutic drugs can penetrate tissues by diffusion and advection. In a healthy tissue, the interstitial fluid is composed of an influx of nutrients and oxygen from blood vessels. In the case of cancerous tissue, the interstitial fluid is poorly drained because of the lack of lymphatic vasculature, resulting in an increase in interstitial pressure. Furthermore, cancer cells invade healthy tissue by pressing and pushing the surrounding environment, creating an increase in pressure inside the tumor area. This results in a large differential pressure between the tumor and the healthy tissue, leading to an increase in extracellular matrix (ECM) stiffness. Because of high interstitial pressure in addition to matrix stiffening, penetration and distribution of systemic therapies are limited to diffusion, decreasing the efficacy of cancer treatment. This work reports on the development of a microfluidic system that mimics in vitro healthy and cancerous microenvironments using collagen I and gelatin methacryloyl (GelMA) composite hydrogels. The microfluidic device developed here contains a simplistic design with a central chamber and two lateral channels. In the central chamber, hydrogel composites were used to mimic the ECM, whereas lateral channels simulated capillary vessels. The transport of fluorescein sodium salt and fluorescently labeled gold nanoparticles from capillary-mimicking channels through the ECM-mimicking hydrogel was explored by tracking fluorescence. By tuning the hydrogel composition and concentration, the impact of the tumor microenvironment properties on the transport of those species was evaluated. In addition, breast cancer MCF-7 cells were embedded in the hydrogel composites, displaying the formation of 3D clusters with high viability and, consequently, the development of an in vitro tumor model.

Physical and Mechanical Characterization of Fibrin-Based Bioprinted Constructs Containing Drug-Releasing Microspheres for Neural Tissue Engineering Applications

“…Crosslinker with and without Microspheres 2.4.1. Indentation Method Elastic moduli of the bioprinted constructs were determined using the modified version of the indentation method for hydrogels [19,31,32,71,72]. Dome-shaped constructs were printed with fibrin-based bioink with and without microsphere and transferred to a 24-well plate.…”

From Dermal Patch to Implants—Applications of Biocomposites in Living Tissues

“…In addition to providing a 3D environment, scaffolds should also match the mechanical properties of the tissue being modelled. Valente et al [89] explored the use of a biocomposite mixture composed of collagen type I and gelatin methacryloyl in order to mimic healthy and cancerous breast tissues. By varying the ratio between these two polymers, different elastic moduli values were obtained for the biocomposites.…”

“…Nanohydroxyapatite and glycol chitosan [10] Hydroxyapatite and polymeric blend (fibroin, chitosan and agarose) [11] Calcium silicate, zinc silicate and graphene oxide [15] Collagen, silk fibroin and dECM [26] Boron nitride and boron trioxide [28] Nanohydroxyapatite, calcium sulfate and bioactive molecules [32] Orthopedic Implants PEEK and graphene oxide [39] CFRPEEK, nanohydroxyapatite, carboxymethyl, chitosan and bone forming peptide [41] Polyphenylene sulfide and nanohydroxyapatite [42] Polyimide and tantalum pentaoxide [43] Hydroxyapatite, ceria nanoparticles and silver nanoparticles [44] Wound Healing Polycaprolactone and gelatin [54] Chitosan, polyethylene oxide and fibrinogen [57] Collagen, alginate and silver nanoparticles [60] Polyurethane, keratin and silver nanoparticles [63] Collagen and dextran [65] Tissue Engineering Fibrin, alginate and genipin [68] PEDOT, chitosan and gelatin [70] Polycaprolactone, silk fibroin and carbon nanotubes [71] Silk fibroin and melanin [78] Polycaprolactone and collagen [82] Gelatin, alginate and fibrinogen [88] Collagen type I and gelatin methacryloyl [89] Author Contributions: Conceptualization, K.P.V., A.B., and A.S.; writing-original draft preparation, K.P.V. ; writing-review and editing, K.P.V., A.B., and A.S.; supervision, A.B.…”

“…(e) Mimicking ECM in vitro using a biocomposite mixture inside of a microfluidic device. Reprinted with permission from Reference[89].…”

Smart Nanotechnologies to Target Tumor with Deep Penetration Depth for Efficient Cancer Treatment and Imaging

“…For the assessment of NPs penetration in vitro, a significant mass of studies chose cancer cell-seeded collagen scaffold, 3D tumor multicellular spheroids and microfluidic tumor model rather than monolayer cells. [178][179][180] This is because these models can better simulate the real transport conditions in tumor extracellular matrix and tumor microenvironment. [181] Tumor spheroids are able to form specific penetration barriers (e.g.…”