Title | Eco-friendly and biocompatible enzymatically cross-linked silk hydrogels for 3D in vitro modeling and cancer research |
Publication Type | Comunications - Poster |
Year of Publication | 2021 |
Authors | Ribeiro V. P., Silva-Correia J., Reis R. L., and Oliveira J. M. |
Abstract | The incidence of cancer in the world has been increasing, which has a major impact on the global healthcare system. Tumors like glioblastoma or osteosarcoma, not only present high metastases rates as the current treatments (e.g., chemotherapy) do not completely satisfy clinic outcomes. Tissue engineering strategies emerged as sustainable solutions for the diagnosis and treatment of cancer. This work aims to develop novel and eco-friendly hydrogel-based in vitro models reflective of tumors heterogeneity and microenvironment. The concept is based on developing more efficient silk fibroin (SF) hydrogels immobilizing human carbonic anhydrase’s (CAs) (HRP-SF/CA), following the horseradish peroxidase(HRP)-mediated cross-linking that reacts with the tyrosine groups (∼5 mol%) on SF and CA (∼4 mol%)[1]. CAs catalyze the reverse hydration of CO2 to produce HCO3- and H+ regulating the pH and metabolic rates of tissues. Moreover, it was found that CA is part of the natural spinning process of fibroin from spiders and silkworms inducing β-sheets’ formation[2]. Thus, it is expected that the immobilization of different isoforms of CAs induce a strong modular character to HRP-SF hydrogels according to tissue requirements and tumor disease modeling. In fact, the catalytic activity of CA-based materials has been proposed for the sequestration of CO2 under mild conditions, which would be highly valuable for controlling carbon emissions to the environment[3]. Herein, the cytosolic CA type II (CAII) was proposed for its role in metabolic regulation of tissues like bone and upregulation in tumors like glioblastoma[4]. The HRP-SF/CAhydrogels showed higher β-sheet content and crystallinity as compared to control HRP-SF hydrogels, according to the CAII concentration (CA-II: 50–450 µg/ml) and oxidizing agent (H2O2, CaO2). Moreover, a positive influence of CA immobilization was observed on U251 glioblastoma cancer cells encapsulated within the matrices up to 7 days of culture. High CA-immobilization efficiency was observed in all tested conditions, and controlled drug release profile from Doxorubicin-loaded HRP-SF/CA hydrogels. Although further studies are necessary to maturate the potential of the HRP-SF/CA matrices to recreate the hypoxic microenvironment of solid tumors in vitro, the preliminary data suggest desirable physicochemical properties of the hydrogels to be further used as bioinks in the design of complex 3D in vitro cancer models. |
Conference Name | Final Forecast Conference |
Date Published | 2021-10-27 |
Conference Location | Fundação Dr. António Cupertino de Miranda, Avenida da Boavista, 4245 4100-140 Porto |
ISSN | 0000 |
ISBN | 00000 |
DOI | 0000000 |
Keywords | 3D in vitro models, cancer research, Carbonic anhydrase, Horseradish peroxidase-cross-linked silk fibroin |
Rights | closedAccess |
Peer reviewed | no |
Status | published |