Tunable Cross-Linking and Adhesion of Gelatin Hydrogels via Bioorthogonal Click Chemistry
| Autor: | Paul T. Sharpe, Ana Angelova Volponi, Adam D. Celiz, Nicola Contessi Negrini |
|---|---|
| Přispěvatelé: | Research England Connecting Capabilities Fund (RE,CCF) Grant, Medical Research Council (MRC) |
| Rok vydání: | 2021 |
| Předmět: |
bioorthogonal cross-linking
gelatin hydrogel food.ingredient hydrogel adhesion 0206 medical engineering Biomedical Engineering 02 engineering and technology Cell morphology Gelatin dental pulp stem cell Biomaterials Tetrazine chemistry.chemical_compound 3D cell culture food 0903 Biomedical Engineering Tissue engineering Humans Tissue Engineering technology industry and agriculture Hydrogels Adhesion 021001 nanoscience & nanotechnology 020601 biomedical engineering degree of modification Cross-Linking Reagents chemistry Chemical engineering Self-healing hydrogels Click chemistry Click Chemistry 0210 nano-technology |
| Zdroj: | ACS biomaterials scienceengineering. 7(9) |
| ISSN: | 2373-9878 |
| Popis: | Engineering cytocompatible hydrogels with tunable physico-mechanical properties as a biomimetic three-dimensional extracellular matrix (ECM) is fundamental to guide cell response and target tissue regeneration or development of in vitro models. Gelatin represents an optimal choice given its ECM biomimetic properties; however, gelatin cross-linking is required to ensure structural stability at physiological temperature (i.e., T > Tsol–gel gelatin). Here, we use a previously developed cross-linking reaction between tetrazine (Tz)- and norbornene (Nb) modified gelatin derivatives to prepare gelatin hydrogels and we demonstrate the possible tuning of their properties by varying their degree of modification (DOM) and the Tz/Nb ratio (R). The percentage DOM of the gelatin derivatives was tuned between 5 and 15%. Hydrogels prepared with higher DOM cross-linked faster (i.e., 10–20 min) compared to hydrogels prepared with lower DOM (i.e., 60–70 min). A higher DOM and equimolar Tz/Nb ratio R resulted in hydrogels with lower weight variation after immersion in PBS at 37 °C. The mechanical properties of the hydrogels were tuned by varying DOM and R by 1 order of magnitude, achieving elastic modulus E values ranging from 0.5 (low DOM and nonequimolar Tz/Nb ratio) to 5 kPa (high DOM and equimolar Tz/Nb ratio). Human dental pulp stem cells were embedded in the hydrogels and successfully 3D cultured in the hydrogels (percentage viable cells >85%). An increase in metabolic activity and a more elongated cell morphology was detected for cells cultured in hydrogels with lower mechanical properties (E < 1 kPa). Hydrogels prepared with an excess of Tz or Nb were successfully adhered and remained in contact during in vitro cultures, highlighting the potential use of these hydrogels as compartmentalized coculture systems. The successful tuning of the gelatin hydrogel properties here developed by controlling their bioorthogonal cross-linking is promising for tissue engineering and in vitro modeling applications. |
| Databáze: | OpenAIRE |
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