Hydrogen sulfide-releasing silk fibroin scaffold for bone tissue engineering

• Published in: Materials Science & Engineering C Vol. 102; pp. 471 - 482
• Main Authors: Gambari, Laura, Amore, Emanuela, Raggio, Rosasilvia, Bonani, Walter, Barone, Marli, Lisignoli, Gina, Grigolo, Brunella, Motta, Antonella, Grassi, Francesco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2019; Elsevier BV
• Subjects: Alizarin; Angiogenesis; Apposition; Assaying; Biocompatibility; Biomedical materials; Bioreactors; Bone growth; Bone healing; Bone marrow; Bone tissue engineering; Bones; Cell adhesion; Cell adhesion & migration; Colonization; Cytotoxicity; Hydrogen sulfide; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Materials science; Mesenchymal stromal cells; Mesenchyme; Metabolism; Mineral metabolism; Mineralization; Ossification; Osteoblastogenesis; Osteoconduction; Osteogenesis; Perfusion; Regeneration; Releasing; Scaffold; Scaffolds; Silk; Silk fibroin; Stromal cells; Target recognition; Tissue engineering; Toxicity; Viability; Hydrogen sulfide; Mesenchymal stromal cells; Silk fibroin; Bone tissue engineering; Scaffold; Osteogenesis
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.04.039

Hydrogen sulfide (H2S)-based therapy is a promising therapeutic strategy for several biomedical applications. Following the observation that endogenous and exogenous H2S plays a prominent role as a bone anabolic agent, we recently developed a silk fibroin (SF) porous scaffold loaded with GYY4137 (GYY), an H2S donor, for applications in bone tissue engineering. Here, we assayed whether the combination of SF with H2S potentiates the osteoconductive properties of SF. Biocompatibility and osteoanabolic activity were assayed in vitro using human bone marrow mesenchymal stromal cells. Cell cultures were performed on a perfusion bioreactor to obtain results closer to the in vivo microenvironment. Cytotoxicity was excluded by lactate dehydrogenase and live/dead assays. Cell colonization and mineral apposition were evaluated by Haematoxylin & Eosin and Von Kossa/Alizarin Red-S stainings respectively. PCR array for human osteogenesis and immunohistochemical analyses were performed to identify pathways and targets involved. Our findings show that H2S-releasing SF scaffolds supported cell adhesion, proliferation and viability. Moreover, H2S activated genes and proteins involved in ossification, osteoblast differentiation, bone mineral metabolism and angiogenesis allowing a high and early mineralization. Based on these properties, we suggest the use of H2S-releasing SF scaffolds for bone healing and regeneration applications. [Display omitted] •Silk fibroin is functionalized with GYY4137 to release hydrogen sulfide (H2S).•H2S-releasing scaffolds induce increased osteogenesis by human stromal cells.•H2S-releasing scaffolds increase the expression of angiogenic factors.•H2S accelerates the deposition of mineral matrix within silk fibroin scaffolds.