Inhibition of BMP9 Induced Bone Formation by Salicylic-acid Polymer Capping
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MRS Advances © 2020 Materials Research Society DOI: 10.1557/adv.2020.61
Inhibition of BMP9 Induced Bone Formation by Salicylic-acid Polymer Capping Timothy M. Acri1, Noah Z. Laird1, Liu Hong2, Jaidev L. Chakka1, Kyungsup Shin2, Satheesh Elangovan2, Aliasger K. Salem1,2 1
University of Iowa, College of Pharmacy, 115 S. Grand Avenue Iowa City, Iowa
2
University of Iowa, College of Dentistry, 801 Newton Road Iowa City, Iowa
Abstract This work focuses on the development of a system to control the formation of bone to complement developments that have enabled potent regeneration of bony tissue. Scaffolds were fabricated with chemically modified RNA encoding for bone morphogenetic protein-9 (cmBMP9) and capped with salicylic acid (SA)-containing polymer (SAPAE). The goal was to determine if SAPAE could inhibit the formation of bone in a pilot animal study since cmBMP9 has been demonstrated to be highly effective in regenerating bone in a rat calvarial defect model. The results indicated that cmBMP9 increased bone formation (30% increase in area covered compared to control) and that SAPAE trended toward reducing the bone formation. These results suggest SAPAE could be useful as a chemical agent in reducing unwanted bone formation in implants loaded with cmBMP9.
INTRODUCTION The field of bone tissue engineering is continually improving with respect to its capacity to successfully regenerate bone tissue under challenging conditions, such as alveolar bone loss [1]. To increase bone formation in clinical applications, bone morphogenetic proteins (BMPs) are incorporated in implants for spinal fusions, long bone fractures, and non-unions [2]. However, with the increase in potency of bone regeneration methods, there is a need to ensure bone forms in the desired location, as use of BMPs can result in heterotopic ossification among other complications [3-5]. The use of anti-inflammatory agents has been experimentally demonstrated to provide a chemical means of reducing bone formation in a local manner [6-9]. Non-steroid anti3505
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inflammatory agents reduce bone formation by inhibiting cyclo-oxygenase 1 (COX-1) and cyclo-oxygenase-2 (COX-2) expression which is thought to be critical for bone turnover [10, 11]. The control of bone formation using this method reduces ectopic bone formation and bony overgrowth caused by growth factors contained within the implant. Additionally, these agents could be combined with guided bone regeneration approaches to chemically inhibit bone formation in addition to physical barriers [12]. The use of agents capable of promoting bone regeneration has been continually advancing and, due to the drawbacks associated with using BMPs in the protein form, progress has been made in developing alternative active agents such as DNA or RNA encoding growth factors that ca
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