Tissue engineering and regenerative approaches to improving the healing of large bone defects
, M. Alini 1,11, E. Alsberg 2,11, S.R. Buchman 3,11, D. Kelly 4,11, M.W. Laschke 5,11, M.D. Menger 5,11, W.L. Murphy 6,11, J.P. Stegemann 7,11, M. Schütz 8,11, T. Miclau 9,11, M.J. Stoddart 1,11, C. Evans 10,111 AO Research Institute Davos, Davos, Switzerland
2 Departments of Biomedical Engineering and Orthopaedic Surgery, Case Western Reserve University, Cleveland, OH, USA
3 Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA
4 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
5 Institute for Clinical and Experimental Surgery, Saarland University, 66421Homburg/Saar, Germany
6 Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA
7 Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
8 Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Australia
9 Department of Orthopaedic Surgery, University of California, San Francisco, Orthopaedic Trauma Institute, University of California, San Francisco/San Francisco General Hospital, San Francisco, CA, USA
10 Rehabilitation Medicine Research Center, Mayo Clinic, 200 First Street SW, Rochester, USA
11 Collaborative Research Partner Large Bone Defect Healing Program of AO Foundation, Davos, Switzerland
Abstract
Despite the high innate regenerative capacity of bone, large osseous defects fail to heal and remain a clinical challenge. Healing such defects requires the formation of large amounts of bone in an environment often rendered hostile to osteogenesis by damage to the surrounding soft tissues and vasculature. In recent years, there have been intensive research efforts directed towards tissue engineering and regenerative approaches designed to overcome this multifaceted challenge. In this paper, we describe and critically evaluate the state-of-the-art approaches to address the various components of this intricate problem. The discussion includes (i) the properties of synthetic and natural scaffolds, their use in conjunction with cell and growth factor delivery, (ii) their vascularisation, (iii) the potential of gene therapies and (iv) the role of the mechanical environment. In particular, we present a critical analysis of where the field stands, and how it can move forward in a coordinated fashion.
Keywords
- Bone
- vascularisation
- scaffolds
- gene therapy
- stem cells
- drug delivery
- large bone defect
- tissue engineering
- regenerative medicine
- translational and preclinical research
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