Smart silk fibroin hydrogels and its potential application as suppressor of angiogenesis and tumor progression

last updated: 2018-12-20
ProjectMultiScaleHuman :: publications list
TitleSmart silk fibroin hydrogels and its potential application as suppressor of angiogenesis and tumor progression
Publication TypeComunications - Poster
Year of Publication2014
AuthorsRibeiro V. P., Silva-Correia J., Miranda-Gonçalves V., Le-Ping Y., Oliveira A. L., Reis R. M., Oliveira J. M., and Reis R. L.

Common methods used to prepare silk fibroin(SF) hydrogels are based on SF conformation transition from amorphous to β-sheet in aqueous status, which implies longer gelation time and harsh preparation conditions [1]. These requirements hinder the final application of SF as injectable system for cell encapsulation/drug delivery. Recently, enzyme-mediated in situ hydrogels attracted great attention because of their specificity and non-toxic nature [2]. Proteins with tyrosine groups can be used to prepare hydrogels in situ using horseradish peroxidase(HRP) and hydrogen peroxide(H2O2) [3]. SF demonstrated to be a promising biomaterial since it contains 5 mol% tyrosine groups. In this study, enzymatically cross-linked SF hydrogels were prepared using high concentrate aqueous SF solution (16 wt%) mediated by a HRP/H2O2 system [4]. The aim of this work is assess the conformation transition in SF hydrogels and evaluate if this transition is allied to potential anti-tumoral applications. The β-sheet conformation transition was analyzed by means of TEM and ThioflavinT staining. Human neuronal glioblastoma (U251) and human cervical adenocarcinoma (HeLa) cells were incorporated into the hydrogels and cultured for 10days under standard culture conditions. Cell viability and proliferation were evaluated through Live/Dead staining and DNA quantification. The fast-formed hydrogels presented mainly amorphous conformation during the first week, but a conversion to a dominant β-sheet conformation was verified from day7. SF hydrogels were capable of incorporating cells and support their viability during the first 24hours of culturing. Nonetheless, the β-sheet conformation of SF induced hydrogels autofluorescence, hindering the cell viability/death evaluation from day7. From DNA quantification it was possible conclude that no cell proliferation occurred from day1 until day10. The obtained results reveal that the conformation transition is responsible for inhibiting cell growth and thus the developed SF hydrogels can be a very useful system for different biomedical applications, including suppressing angiogenesis and tumors progression in vivo.


Conference Name4th ICVS/3Bs Meeting
Date Published2014-11-10
Conference LocationBraga, Portugal
KeywordsAngiogenesis, Anti-tumoral, cell encapsulation, Enzyme-mediated in situ hydrogelation, Silk fibroin hydrogel, β-sheet conformation
Peer reviewedyes

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