title: In vitro cyclic compressive loads potentiate early osteogenic events in engineered bone tissue.
abstract: Application of dynamic mechanical loads on bone and bone explants has been reported to enhance osteogenesis and mineralization. To date, published studies have incorporated a range of cyclic strains on 3D scaffolds and platforms to demonstrate the effect of mechanical loading on osteogenesis. However, most of the loading parameters used in these studies do not emulate the in vivo loading conditions. In addition, the scaffolds/platforms are not representative of the native osteoinductive environment of bone tissue and hence may not be entirely accurate to study the in vivo mechanical loading. We hypothesized that biomimicry of physiological loading will potentiate accelerated osteogenesis in bone grafts. In this study, we present a compression bioreactor system that applies cyclic compression to cellular grafts in a controlled manner. Polycaprolactone-β Tricalcium Phosphate (PCL-TCP) scaffolds seeded with Mesenchymal Stem Cells (MSC) were cyclically compressed in bioreactor for a period of 4 weeks at 1 Hz and physiological strain value of 0.22% for 4 h per day. Gene expression studies revealed increased expressions of osteogenesis-related genes (Osteonectin and COL1A1) on day 7 of cyclic loading group relative to its static controls. Cyclic compression resulted in a 3.76-fold increase in the activity of Alkaline Phosphatase (ALP) on day 14 when compared to its static group (p < 0.001). In addition, calcium deposition of cyclic loading group was found to attain saturation on day 14 (1.96 fold higher than its static scaffolds). The results suggested that cyclic, physiological compression of stem cell-seeded scaffolds generated highly mineralized bone grafts. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2366-2375, 2017.
authors.affiliation: Centre for Bone Tissue Engineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
authors.forename: Akhilandeshwari
authors.initials: A
authors.lastname: Ravichandran
authors.affiliation: Centre for Bone Tissue Engineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Lim
authors.affiliation: Centre for Bone Tissue Engineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
authors.forename: Mark Seow Khoon
authors.initials: MSK
authors.lastname: Chong
authors.affiliation: Centre for Bone Tissue Engineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
authors.forename: Feng
authors.initials: F
authors.lastname: Wen
authors.affiliation: Centre for Bone Tissue Engineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.|Academic Clinical Program (Research), National Dental Centre of Singapore, Singapore 168938, Singapore.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medicine and Medical Science, School of Medicine, University College Dublin, Dublin, Ireland.
authors.forename: Yaesshna T
authors.initials: YT
authors.lastname: Pillay
authors.affiliation: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.|Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore.|Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Jerry K Y
authors.initials: JKY
authors.lastname: Chan
authors.affiliation: Centre for Bone Tissue Engineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
authors.forename: Swee-Hin
authors.initials: SH
authors.lastname: Teoh
mesh_terms: D019149:Bioreactors; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002130:Calcium Phosphates / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis; D011091:Polyesters / Q000737:chemistry; D013314:Stress, Mechanical; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D002130:Calcium Phosphates; D011091:Polyesters; C485817:beta-tricalcium phosphate; C016240:polycaprolactone
keywords: bioreactors; bone tissue engineering; mechanical loading; mesenchymal stem cells; polymeric scaffolds