Semi‐interpenetrating polymer network cryogels based on poly(ethylene glycol) diacrylate and collagen as potential off‐the‐shelf platforms for cancer cell research

Abstract

In the present work, we investigated the potential of novel semi-interpenetrating polymer network (semi-IPN) cryogels, obtained through ultraviolet exposure of aqueous mixtures of poly(ethylene glycol) diacrylate and type I collagen, as tunable offthe-shelf platforms for 3D cancer cell research. We synthesized semi-IPN cryogels with variable collagen amounts (0.1% and 1% w/v) and assessed the effect of collagen on key cryogel properties for cell culture, for example, porosity, degradation rate and mechanical stiffness. Then, we investigated the ability of the cryogels to sustain the long-term growth of two pancreatic ductal adenocarcinoma (PDAC) cell populations, the parenchymal Panc1 cells and their derived cancer stem cells. Results revealed that both cell lines efficiently infiltrated, attached and expanded in the cryogels over a period of 14 days. However, only when grown in the cryogels with the highest collagen concentration, both cell lines reproduced their characteristic growth pattern previously observed in collagen-enriched organotypic cultures, biomimetic of the highly fibrotic PDAC stroma. Cellular preembedding in Matrigel, that is, the classical approach to develop/grow organoids, interfered with an efficient intrascaffold migration and growth. Although preliminary, these findings highlight the potential of the proposed cryogels as reproducible and tunable cancer cell research platforms.

Design and Assessment of Biodegradable Macroporous Cryogels as Advanced Tissue Engineering and Drug Carrying Materials

“…Facilitates cancer cell invasion, migration and proliferation allowing for comprehensive characteristic of tumor cell behavior and testing the activity of anticancer drugs [29] Hyaluronic acid-PEG Immobilized biomimetic ligands offer control over cellular response resulting in enhanced spreading with RGD and formation of 3D cell spheroids with IKVAV [161] HEMA-Alginate-Gelatin 3D culturing of prostate cancer cells and spheroids to study their progression and behavior [188] Poly(ethylene glycol) diacrylate and type I collagen semi-interpenetrating polymer network cryogels Tunable off-the-shelf platforms for 3D cancer cell [112] Drug delivery HEMA-Gelatin pH-responsive release of doxorubicin with increased rate in more acidic conditions mimicking tumor environment [30] Inulin cryogel Release of amoxicillin trihydrate [85] Alginate beads Release of quercetin as antioxidant [19] Chitosan, hydroxyapatite, heparin, and polyvinyl alcohol composite Release of bone morphogenic protein 2 and support of the differentiation of rat bone marrow mesenchymal stem cells.…”

“…Coating with polydopamine increased the viability (by 52%) and proliferation (by 33%) of mesenchymal stem cells in dopamine-modified collagen cryogels compared to non-modified ones [ 103 ]. Pure collagen is often used to form a scaffold, not alone but in combination with various materials, as discussed in other sections [ 90 , 91 , 112 ].…”

“…Significant degradation of PEGDA hydrogels occurred over 12 weeks In Vivo as a result of hydrolysis of the PEGDA end groups esters. PEG cryogels were synthesized by radical polymerization of PEGDA using APS/TEMED [ 128 , 129 , 130 ] or via UV radiation [ 112 , 131 ]. The morphology and swelling of the PEG cryogels were controlled by the freezing temperature and initiator concentration [ 58 ] and depended on the PEGDA concentration [ 131 ].…”