title: Evaluating the feasibility of utilizing the small molecule phenamil as a novel biofactor for bone regenerative engineering.
abstract: Osteoblast cell adhesion and differentiation on biomaterials are important achievements necessary for implants to be useful in bone regenerative engineering. Recombinant bone morphogenetic proteins (BMPs) have been shown to be important for these processes; however, there are many challenges associated with the widespread use of these proteins. A recent report demonstrated that the small molecule phenamil, a diuretic derivative, was able to induce osteoblast differentiation and mineralization in vitro via the canonical BMP signalling cascade (Park et al., 2009). In this study, the feasibility of using phenamil as a novel biofactor in conjunction with a biodegradable poly(lactide-co-glycolide acid) (PLAGA) polymeric scaffold for engineering bone tissue was evaluated. The in vitro cellular behaviour of osteoblast-like MC3T3-E1 cells cultured on PLAGA scaffolds in the presence of phenamil at 10 μM were characterized with regard to initial cell adhesion, proliferation, alkaline phosphatase (ALP) activity and matrix mineralization. The results demonstrate that phenamil supported cell proliferation, promoted ALP activity and facilitated matrix mineralization of osteoblast-like MC3T3-E1 cells. Moreover, in this study, we found that phenamil promoted integrin-mediated cell adhesion on PLAGA scaffolds. It was also shown that phenamil encapsulated within porous, microsphere PLAGA scaffolds retained its osteogenic activity upon release. Based on these findings, the small molecule phenamil has the potential to serve as a novel biofactor for the repair and regeneration of bone tissues.
authors: Institute for Regenerative Engineering, University of Connecticut Health Center, School of Medicine, Farmington, CT, USA; Department of Medicine, Division of Endocrinology, University of Connecticut Health Center, School of Medicine, Farmington, CT, USA.
authors: Kevin W-H
authors: KW
authors: Lo
authors: Bret D
authors: BD
authors: Ulery
authors: Ho Man
authors: HM
authors: Kan
authors: Keshia M
authors: KM
authors: Ashe
authors: Cato T
authors: CT
authors: Laurencin
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001857:Bone Matrix / Q000187:drug effects / Q000502:physiology; D001861:Bone Regeneration / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005240:Feasibility Studies; D019344:Lactic Acid / Q000494:pharmacology; D051379:Mice; D008863:Microspheres; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D054852:Small Molecule Libraries / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D054852:Small Molecule Libraries; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C047088:phenylamil; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000584:Amiloride; D000469:Alkaline Phosphatase