Robert Pilliar, Professor emeritus, Faculty of Dentistry and Institute of Biomaterials and Biomedical Engineering, University of Toronto, Canada
Porous Calcium Polyphosphates – Biodegradable Bone Substitutes and Beyond
Calcium polyphosphates (CPP) are linear inorganic polymers that can be processed to form biodegradable porous structures for use as bone substitutes. Like other calcium phosphates, their degradation in vivo with release of Ca2+ and PO43- ions is conducive to new bone formation making them attractive either in porous particulate or porous bulk structure form for repair and regeneration of bone defects. Processing of porous CPP can be achieved by sintering amorphous CPP powders to desired densities and subsequent higher temperature annealing to achieve porous β-CPP crystalline structures having appropriate initial mechanical properties for moderate load-bearing applications and degradation characteristics to allow gradual substitution by newly-formed bone. Use of additive manufacturing (AM) + post-AM thermal processing allows preparation of customized bone substitutes for defect site repair in shapes and sizes as defined through pre-clinical CT imaging. The major challenge in preparing such customized bone substitutes is to achieve degradation of the porous CPP implants at an appropriate rate to allow their replacement in a timely manner by structurally sound bone. Appropriate processing conditions including cation doping have been shown effective for controlling both degradation rate and initial mechanical properties.
Porous calcium polyphosphate constructs are also being investigated for preparation of customized osteochondral implants for repair and regeneration of localized skeletal joint defects and, potentially, whole joint regeneration. This can be achieved by preparation of desired forms of porous CPP constructs using 3D printing (again guided by CT imaging input) on which articular cartilage layers can be formed over articulating surfaces. This is achieved by in vitro cartilage formation using tissue culturing methods prior to implantation of the resulting biphasic (i.e. cartilage + CPP) implants in intended sites. Through the in vitro processing, newly-formed cartilage can be formed and secured to the porous CPP construct on the intended articulation surface by ingrowth and interdigitation with the porous CPP. On implantation, the biphasic implant so formed becomes securely affixed to host bone by bone ingrowth thereby providing a template for osteochondral defect repair by natural tissue (bone and cartilage) regeneration. With gradual biodegradation of the porous CPP and its substitution by new bone, cartilage-subchondral bone regeneration is achieved. The challenges for successfully achieving such localized defect repair and, in certain sites, whole joint regeneration are; i) achieving an appropriate rate of CPP degradation to allow its uninhibited substitution by bone, ii) ensuring initial formation and maintenance of a sufficiently strong cartilage-to-CPP and, subsequently, cartilage-to-bone interface to resist imposed forces acting at the bearing surface and iii) allowing acceptable maturation of cartilage and bone remodeling over time.
Progress in studies towards these goals will be presented.
Serena M. Best, Cambridge Centre for Medical Materials, Department of Materials Science and Metallurgy, University of Cambridge
Optimizing Bioactive Scaffolds: Cellular Response to Calcium Phosphate Composition and Architecture
There have been a number of examples of successful translation of bioceramics research into clinical products over the past 40 years. In the field of orthopaedic surgery, the development of calcium phosphates has shown particular potential, due to their similarity with the chemical composition of bone mineral. Hydroxyapatite (Ca10(PO4)6(OH)2) has been of particular interest due to the ability to control composition by making chemical substitutions in the crystal lattice, which encourage bone repair. It is understood that even small changes in elemental- and phase “impurity” content can influence the biological response to the implant. Going forward, the field of tissue engineering (in bone grafting, for example) relies on the supply of high quality three dimensional scaffolds and their architecture contributes significantly to performance, This presentation will review historic and recent developments to understand the control of physical and chemical characteristics of bioactive ceramics for optimised biological response.