Influence of biological factors on the mechanical regulation of tissue differentiation processes during large bone-defect healing.
Final Report Abstract
The elucidation of the mechanical “rules” driving bone regeneration has been the focus of many studies during the last 30 years, since such knowledge has a great relevance in the design of clinical strategies for the treatment of bone fractures. However, so far investigations about the mechanical regulation of the bone healing response have focused on uneventful healing conditions; i.e. situations where bone bridging is achieved. The goal of our project was to better understand the mechanical regulation of clinically challenging cases characterized for being compromised healing conditions; i.e. conditions which would eventually lead to delayed or non-union cases. Specifically, we investigated the bone healing response during large bone defect healing with and without biological stimulation. We showed that mechanics play a key role in bone healing progression, both in uneventful and large defect healing and that BMP-2 stimulated healing could be explained by an increase in biological activity while maintaining the bone response to mechanical loading. In addition, we investigated alterations in the bone response to mechanical loading with aging. We showed that under the same external load, strains engendered in bone are reduced with increasing age, which could mainly be attributed to age-related changes in the bone morphology and less to alterations in tissue material properties. We also showed that independent of age, formation and resorption are mechano-regulated, preferentially at high strains. However, with increasing age mechanically induced (re)modeling becomes dysregulated, apparent in an inability to inhibit resorption or initiate formation. Further studies will focus on age-related alterations in the mechanical regulation of bone healing. We believe that findings from our present and future studies will help to provide a framework for understanding how regenerative medicine approaches might be combined with mechanical loading or exercise to most effectively combat age-related bone loss or treat bone defects in aged patients.
Publications
- (2014) A finite element model of in vivo mouse tibial compression loading: influence of boundary conditions. Facta Universitatis. Series: Mechanical Engineering Vol. 12, No 3, 2014, pp. 195 - 207
Razi H, Birkhold AI, Zehn M, Duda GN, Willie B, Checa S
- (2014) Investigation of different cage designs and mechano-regulation algorithms in the lumbar interbody fusion process - a finite element analysis. J Biomech.,47(6): 1514-9
Postigo S, Schmidt H, Rohlmann A, Putzier M, Simón A, Duda GN, Checa S
(See online at https://doi.org/10.1016/j.jbiomech.2014.02.005) - (2014) The Emergence of Extracellular Matrix Mechanics and Cell Traction Forces as Important Regulators of Cellular Self-organization. Biomechanics and Modeling in Mechanobiology, 14(1):1-13
Checa S, Rausch M, Petersen A, Kuhl E, Duda GN
(See online at https://doi.org/10.1007/s10237-014-0581-9) - Age-related changes in the mouse tibia morphology lead to reduced mechanical strain under external loading, Acta Biomaterialia, 13:301- 10, 2015
Razi H, Birkhold A, Zaslansky P, Weinkamer R, Duda GN, Willie BM, Checa S
(See online at https://doi.org/10.1016/j.actbio.2014.11.021) - Aging leads to a loss in the mechanical regulation of bone formation and resorption, Journal of Bone and Mineral Research, Apr 9, 2015
Razi H, Birkhold A, Weinkamer R, Duda GN, Willie BM, Checa S
(See online at https://doi.org/10.1002/jbmr.2528) - Effect of in vivo loading on bone composition varies with animal age, Experimental Gerontology, 63:48-58, 2015
Aido M, Kerschnitzsky M, Hoerth R, Checa S, Spevak L, Boskey A, Fratzl P, Duda GN, Wagermaier W, Willie BM
(See online at https://doi.org/10.1016/j.exger.2015.01.048) - Maturation substantially affects elastic tissue properties in the endosteal and periosteal regions of loaded mice tibias, Acta Biomaterialia, 21:154-64, 2015
Checa S, Hesse B, Roschger P, Aido M, Raum K, Duda GN, Willie BM
(See online at https://doi.org/10.1016/j.actbio.2015.04.020)
