3rd Australia–China Biomedical Research Conference (ACBRC2011) Role of chemical and mechanical stimuli in mediating bone fracture healing Lihai Zhang,* Martin Richardson † and Priyan Mendis* Departments of *Infrastructure Engineering and † Anatomy and Cell Biology, The University of Melbourne, Melbourne, Victoria, Australia SUMMARY 1. Bone is a remarkable living tissue that provides a frame- work for animal body support and motion. However, under excessive loads and deformations, bone is prone is to damage through fracture. Furthermore, once the bone is weakened by osteoporosis, bone fracture can occur even after only minimal trauma. 2. Various techniques have been developed to treat bone frac- tures. Successful treatment outcomes depend on a fundamental understanding of the biochemical and biomechanical environ- ments of the fracture site. Various cell types (e.g. mesenchymal stem cells, chondrocytes, osteoblasts and osteoclasts) within the fracture site tightly control the healing process by responding to the chemical and mechanical microenvironment. However, these mechanochemical regulatory mechanisms remain poorly under- stood at the system level owing to the large range of variables, such as age, sex and disease-associated material properties of the tissue. 3. Computational modelling can play an important role in unravelling this complexity by combining mechanochemical interactions, revealing the dominant controlling processes and optimizing system behaviour, thereby enabling the development and evaluation of treatment strategies for individual patients. Key words: biomaterials, biomechanics, bone, growth factors. INTRODUCTION Osteoporosis, which is most prevalent among the elderly, is an expensive disease to manage. In Australia, 35% of people aged 70–79 years and 50.1% of people over 80 years of age suffer from this condition. 1 An estimated 3 million Australians will have osteo- porosis by 2021, with a fracture occurring every 3.5 min. 1 In 2001, the direct costs of osteoporosis in Australia amounted to $1.9 billion (approximately 1.2% of GDP). 2 Indirect costs, such as lost earnings and volunteer support, accounted for another $5.6 billion 2 . Pain and suffering resulting from osteoporotic bone fracture may significantly decrease the quality of life of patients. An improved understanding of the mechanisms underlying bone fracture healing may help in the development of new strategies for the management of osteoporotic bone fracture. Bone is a remarkable living tissue that is composed of cells, water and extracellular matrix (ECM). Specialized bone cells regulate the process of bone remodelling through synthesis and dissolution in response to the biochemical and biomechanical microenvironment, thereby maintaining the homeostasis and biological functions of bone tissue. 3 Bone ECM consists of an organic phase (i.e. primarily colla- gen and other proteins) and a mineral phase (i.e. primarily crystalline hydroxyapatite and other mineral substances). The organic phase pro- vides resistance to tension, whereas the mineral phase is mainly responsible for compression. 4 Under unusual loads and deformations that exceed its strength, bone may fracture. However, once the bone is weakened by osteoporosis, bone fracture is prone to occur even after only minimal trauma. After bone fracture, a natural healing process occurs that involves the formation of a fracture callus to stabilize the fracture site. This process involves the migration and proliferation of cells (e.g. mesen- chymal stem cells) and ultimately restores the original bone structure and shape. 4 Depending on the size of the fracture gap and the mechanical stability, fracture healing can occur in one of two main ways: 5 (i) primary bone healing occurs in minimally comminuted fractures fixed in compression (absolute stability) and involves mini- mal callus formation; and (ii) secondary bone healing occurs with rel- atively stable fixation techniques and involves callus development. The main difference between these two healing processes is the formation of the fracture callus. Most bone fractures involve secondary bone healing, which is normally divided into four major stages (i.e. inflammation, callus differentiation, ossification and remodelling). 5 The inflammatory phase starts immediately after injury and lasts approximately 2 weeks. During this period, haematoma formation results from the disruption of blood vessels. Most importantly, mesenchymal stem cells trigger the initial formation of a fracture callus, releasing growth factors. During the callus differentiation stage, granulation tissue is Correspondence: Dr L Zhang, Department of Infrastructure Engineering, The University of Melbourne, Victoria 3010, Australia. Email: lihzhang@ unimelb.edu.au Presented at the 3rd Australia–China Biomedical Research Conference (ACBRC2011) Melbourne, Australia, 28–30 April 2011. The papers in these proceedings have been peer reviewed. Received 29 June 2011; revision 27 November 2011; accepted 30 November 2011. Ó 2011 The Authors Clinical and Experimental Pharmacology and Physiology Ó 2011 Blackwell Publishing Asia Pty Ltd Clinical and Experimental Pharmacology and Physiology (2012) 39, 706–710 doi: 10.1111/j.1440-1681.2011.05652.x