@article {48079,
	title = {Silk fibroin microparticle scaffold for use in bone void filling: safety and efficacy studies},
	journal = {ACS Biomaterials Science \& Engineering},
	volume = {8},
	year = {2022},
	month = {MAR},
	pages = {1226-1238},
	type = {Article},
	abstract = {<p>
	Silk fibroin (SF) is a natural biocompatible protein polymer extracted from cocoons of silkworm Bombyx mori. SF can be processed into a variety of different forms and shapes that can be used as scaffolds to support bone regeneration. Threedimensional (3D) SF scaffolds have shown promise in bone-void -filling applications. In in vitro studies, it has been demonstrated that a microparticle-based SF (M-RSF) scaffold promotes the differentiation of stem cells into an osteoblastic lineage. The expression of differentiation markers was also significantly higher for M-RSF scaffolds as compared to other SF scaffolds and commercial ceramic scaffolds. In this work, we have evaluated the in vitro and in vivo biocompatibility of M-RSF scaffolds as per the ISO 10993 guidelines in a Good Laboratory Practice (GLP)-certified facility. The cytotoxicity, immunogenicity, genotoxicity, systemic toxicity, and implantation studies confirmed that the M-RSF scaffold is biocompatible. Further, the performance of the MRSF scaffold to support bone formation was evaluated in in vivo bone implantation studies in a rabbit model. Calcium sulfate (CaSO4) scaffolds were chosen as reference material for this study as they are one of the preferred materials for bone-void -filling applications. M-RSF scaffold implantation sites showed a higher number of osteoblast and osteoclast cells as compared to CaSO4 implantation sites indicating active bone remodeling. The number density of osteocytes was double for M-RSF scaffold implantation sites, and these M-RSF scaffold implantation sites were characterized by enhanced collagen deposition, pointing toward a finer quality of the new bone formed. Moreover, the M-RSF scaffold implantation sites had a negligible incidence of secondary fractures as compared to the CaSO4 implantation sites (similar to 50\% sites with secondary fracture), implying a reduction in postsurgical complications. Thus, the study demonstrates that the M-RSF scaffold is nontoxic for bone-void -filling applications and facilitates superior healing of fracture defects as compared to commercial calcium-based bone void fillers.</p>
},
	keywords = {Biocompatibility, biological safety, bone void filler, ISO 10993, M-RSF, Serioss, Silk fibroin},
	issn = {2373-9878},
	doi = {10.1021/acsbiomaterials.1c01103},
	author = {Deshpande, Rucha and Shukla, Swati and Kale, Amod and Deshmukh, Narendra and Nisal, Anuya and Venugopalan, Premnath}
}
