Laomeephol Chavee, Ferreira Helena, Kanokpanont Sorada, Luckanagul Jittima Amie, Neves Nuno M, Damrongsakkul Siriporn
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Biomaterial Engineering for Medical and Health Research Unit, Chulalongkorn University, Bangkok, Thailand.
Biomater Transl. 2022 Sep 28;3(3):213-220. doi: 10.12336/biomatertransl.2022.03.005. eCollection 2022.
The tissue engineering triad comprises the combination of cells, scaffolds and biological factors. Therefore, we prepared cell- and drug-loaded hydrogels using in situ silk fibroin (SF) hydrogels induced by dimyristoyl glycerophosphoglycerol (DMPG). DMPG is reported to induce rapid hydrogel formation by SF, facilitating cell encapsulation in the hydrogel matrix while maintaining high cell viability and proliferative capacity. In addition, DMPG can be used for liposome formulations in entrapping drug molecules. Dexamethasone (Dex) was loaded into the DMPG-induced SF hydrogels together with human osteoblast-like SaOS-2 cells, then the osteogenic differentiation of the entrapped cells was evaluated in vitro and compared to cells cultured under standard conditions. Calcium production by cells cultured in DMPG/Dex-SF hydrogels with Dex-depleted osteogenic medium was equivalent to that of cells cultured in conventional osteogenic medium containing Dex. The extended-release of the entrapped Dex by the hydrogels was able to provide a sufficient drug amount for osteogenic induction. The controlled release of Dex was also advantageous for cell viability even though its dose in the hydrogels was far higher than that in osteogenic medium. The results confirmed the possibility of using DMPG-induced SF hydrogels to enable dual cell and drug encapsulation to fulfil the practical applications of tissue-engineered constructs.
组织工程三元组包括细胞、支架和生物因子的组合。因此，我们使用由二肉豆蔻酰甘油磷酸甘油（DMPG）诱导的原位丝素蛋白（SF）水凝胶制备了负载细胞和药物的水凝胶。据报道，DMPG可诱导SF快速形成水凝胶，便于细胞包裹在水凝胶基质中，同时保持高细胞活力和增殖能力。此外，DMPG可用于脂质体制剂以包裹药物分子。将地塞米松（Dex）与人成骨样细胞SaOS-2一起负载到DMPG诱导的SF水凝胶中，然后在体外评估包裹细胞的成骨分化，并与在标准条件下培养的细胞进行比较。在不含Dex的成骨培养基中培养于DMPG/Dex-SF水凝胶中的细胞产生的钙与在含Dex的传统成骨培养基中培养的细胞相当。水凝胶对包裹的Dex的缓释能够为成骨诱导提供足够的药物量。即使水凝胶中Dex的剂量远高于成骨培养基中的剂量，其控释对细胞活力也有利。结果证实了使用DMPG诱导的SF水凝胶实现细胞和药物双重包裹以满足组织工程构建体实际应用的可能性。
