title: Controlling cell biomechanics in orthopaedic tissue engineering and repair.
abstract: Tissue engineering offers an alternative approach with great potential for the treatment or replacement of damaged tissues or organs. In contrast to current treatments, a small sample of cells can be collected from the patient and cultured in vitro, greatly increasing the number of cells available for engineering tissue implants. As a result, engineered tissue implants limit the problems associated with patient trauma and undesirable immune response currently observed in surgical treatments practised in tissue and organ replacement. Mechano-transduction is known to play an essential role in bone tissue remodelling and repair. At physiological magnitudes, the effects of secondary messenger pathways, their components and local mediators generated as a direct result of mechanical load are known to result in an elevation of specific matrix protein mRNAs. Up-regulation of matrix protein production is paramount to tissue formation. Thus, mechano-transduction offers a method of producing bone tissue in vitro. However, successful transduction of mechanical stimuli from a substrate to cells is reliant upon a number of factors including cell-substrate adhesion, scaffold material mechanics and the activation of membrane channels, for example voltage-operated calcium channels (VOCC). Our research focuses on the optimisation of mechano-transduction pathways for successful bone tissue engineering. In this paper, we focus on the effects of cell-substrate adhesion, attenuation of VOCC activation states and biological conditioning of cell-scaffold constructs utilising bioreactors in relation to mechano-transduction-induced bone tissue production. The effects of these factors on successful bone tissue formation observed in increased matrix protein synthesis due to the optimisation of mechano-transduction pathways is discussed.
authors.affiliation: Institute of Science and Technology in Medicine, Keele University Medical School, University Hospital of North Staffordshire, Hartshill, Stoke-on-Trent ST4 7QB, UK. bea17@keele.ac.uk
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: El Haj
authors.forename: Mairead A
authors.initials: MA
authors.lastname: Wood
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D019149:Bioreactors; D001857:Bone Matrix / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002460:Cell Line; D002478:Cells, Cultured / Q000637:transplantation; D005898:Glass; D006801:Humans; D018472:Hypogravity; D040542:Mechanotransduction, Cellular; D019637:Orthopedic Procedures / Q000379:methods*; D009985:Orthopedics; D011108:Polymers; D011312:Pressure; D013499:Surface Properties; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D002120:Calcium Channel Agonists; D015220:Calcium Channels; D011108:Polymers; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester