Affiliation:
1. Department of Biologic and Materials Sciences and Prosthodontics, School of Dentistry University of Michigan Ann Arbor Michigan USA
2. Department of Dental Biomaterials Faculty of Dentistry, Mansoura University Mansoura Egypt
3. Department of Dental Biomaterials, Faculty of Oral and Dental Medicine Delta University for Science and Technology Dakahlia Egypt
4. Department of Dental Biomaterials, Faculty of Dentistry October 6 University Cairo Egypt
5. Department of Dental Biomaterials, Faculty of Oral and Dental Medicine Cairo University Cairo Egypt
Abstract
AbstractStimuli‐responsive domains capable of releasing loaded molecules, “on‐demand,” have garnered increasing attention due to their enhanced delivery, precision targeting, and decreased adverse effects. The development of an on‐demand delivery system that can be easily triggered by dental clinicians might have major roles in dental and oral tissue engineering. A series of random graft poly(NIPAm‐co‐HEMA‐Lactate) copolymers were synthesized using 95:5, 85:5, 60:40, and 40:60 ratios of thermosensitive NIPAm and HEMA‐poly lactate respectively then electrospun to produce nanofibrous scaffolds loaded with bovine serum albumin (BSA). Cumulative BSA release was assessed at 25C and 37°C. To appraise the use of scaffolds as on‐demand delivery systems, they were subjected to thermal changes in the form cooling and warming cycles during which BSA release was monitored. To confirm the triggered releasing ability of the synthesized scaffolds, the copolymer made with 60% NIPAm was selected, based on the results of the release tests, and loaded with bone morphogenetic protein‐2 (BMP‐2). The loaded scaffolds were placed with mesenchymal‐like stem cells (iMSCs) derived from induced pluripotent stem cells (iPSCs), and subjected to temperature alterations. Then, the osteogenic differentiation of iMSCs, which might have resulted from the released protein, was evaluated after 10 days by analyzing runt‐related transcription factor 2 (RUNX‐2) osteogenic gene expression by the cells using real‐time quantitative polymerase chain reaction (qRT‐PCR). BSA release profiles showed a burst release at the beginning followed by a more linear pattern at 25°C, and a much slower release at 37°C. The release also decreased when the PNIPAm content decreased in the scaffolds. Thermal triggering led to a step‐like release pattern in which the highest release was reported 30 min through the warming cycles. The iMSCs cultivated with scaffolds loaded with BMP‐2 and exposed to temperature alteration showed significantly higher RUNX‐2 gene expression than cells in the other experimental groups. The synthesized scaffolds are thermo‐responsive and could be triggered to deliver biological biomolecules to be used in oral and dental tissue engineering. Thermal stimuli could be simulated by dental clinicians using simple means of cold therapy, for example, cold packs in intraoral accessible sites for specified times.
Funder
Ministry of Education – Kingdom of Saudi Arabi
Subject
Metals and Alloys,Biomedical Engineering,Biomaterials,Ceramics and Composites