University of the Punjab Conference Portal, 2nd International Conference on Engineering Sciences

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Bioactive Materials for Regenerative Medicine [ Keynote Lecture by Prof. Dr. Ihtesham ur Rehman from UK]
Ihtesham ur Rehman

Last modified: 2015-11-20

Abstract


Bone trauma causes pain and restricted movement. Bone tissue engineering involves the use of natural and/or synthetic materials in combination with cells to promote bone regeneration. Hard tissue replacement required as a result of loss through disease or trauma is an area of intense importance. The aim of all bone replacement materials should be to match the biological and mechanical properties of the bone being replaced. Two forms of natural bone that provide structural support are known as cortical bone and cancellous bone. Cancellous bone has a sponge-like structure and its biomechanical behaviour approximates to an isotropic material. Cortical bone is however highly anisotropic, with reinforcing structures, osteons, aligned to support its major loading axis and a complex microstructure, typically containing collagen fibres (Type 1, 16%), biological apatite (inorganics, 60%), water (23 %) and ground substance (proteins, polysaccharides, etc. at 2 %).  At present, there are few credible synthetic alternatives for replacement of medium to high-load bearing bones. Current clinical treatments for replacement of cortical bone use the patient's own bone from the lilac crest. Thus, there is a real clinical need for improving replacement hard tissue substitutes that do not carry a possibility of tissue rejection or possible transmission of disease. It is not just the complex structure or excellent mechanical properties of natural bone that are difficult to mimic, it is the dynamic capability of bone to remodel. Almost without exception, natural tissues can regenerate or remodel depending on the loading requirements. The bone replacement materials that have been developed over the years include (Hapexä, a polyethylene/ hydroxyapatite composite ), contain a bioactive, bone-bonding constituent and a polymer matrix that is essentially non-degradable and unable to be replaced by new bone. Attention has been on the use of high strength matrices that are gradually replaced by new tissue in situ without loss of mechanical integrity. There have been several credible effeorts of resorbable polymer/ceramic biocomposites based on either polylactic acid (PLA) or polyglycolic acid (PGA) matrices. The addition of randomly orientated chopped fibres (either coupled or uncoupled) has improved the mechanical properties, however, these implants fail mechanically due to insufficient new bone formation as the composite degrades. PLA / tri-calcium phosphate (TCP) composites with a fracture strength of 50 MPa (i.e. 30 - 50% of cortical bone) have been obtained.  A credible synthetic replacement for cortical bone is required to possess a bioactive interface with surrounding tissues whilst being resorbed over time, and be able to support significant loads as new bone is formed. The advantages of this approach are that: (i) the matrix will not fail during remodelling due to applied mechanical stresses and (ii) a second operation is not required because the implant is replaced in situ.

 In this paper, advances in bone regeneration both in load bearing and non-load bearing applications will be highlighted. Our recent work on developing new bone scaffolds by tissue engineering applications and regeneration of periodontal tissue will be highlighted. The Young's modulus, fracture toughness and ultimate tensile strength of the composite (grafted or otherwise) are governed by the volume fraction (Vf) of the individual components and the extent of bonding between phases. Volume fractions of ceramic particles, rods, hollow fibres and chopped fibres will range from 0-50%. This equates to a weight percentages (wt%) of up to ca. 70%. Cortical bone is an anisotropic material (it has greater strength in the load bearing axis), thus we aim to manufacture anisotropic polymer composites using conventional fibre matrix composite forming methodology (ceramic bundles / fibre matting for reinforcing phase), composite forming embodiments of (i) grafted powders, (ii) grafted chopped fibres (iii) grafted aligned fibres and (iv) grafted fibre matting. In particular, stacks of pre-grafted bioactive ceramic fibre/particles matting react with pre-polymers to form anisotropic composite mats. These were pressed to attain high strength whilst retaining high interfacial cohesion. The bioactive composites were manufactured to incorporate a degree of macroporosity (diameters in the range 150 - 250 microns) in the polymer phase to allow some vascular flow and new bone in-growth. As a result of the grafting phenomena and porosity of the composites, the resorbability and effective bioactivity of the grafted bioactive phase was obtained. Fabrication techniques such as, freeze gelation, electro spraying and solvent castings were employed. Materials obtained were characterised for their biological, physical, chemical and mechanical properties. Fabricated Guided tissue regeneration (GTR) membranes9 were used for the management of destructive forms of periodontal disease as a means of aiding regeneration of lost supporting tissues, including the alveolar bone, cementum, gingiva and periodontal ligaments (PDL). Currently available GTR membranes are either non-biodegradable, requiring a second surgery for removal, or biodegradable. The mechanical and biofunctional limitations of currently available membranes result in a limited and unpredictable treatment outcome in terms of periodontal tissue regeneration. In this study, porous membranes of chitosan (CH) were fabricated with or without hydroxyapatite (HA) using the simple technique of freeze gelation (FG) via two different solvents systems, acetic acid (ACa) or ascorbic acid (ASa). The aim was to prepare porous membranes to be used for GTR to improve periodontal regeneration.


References


1. A.S. Khan, K.R. Hassan, S.F. Bukhari, F.S.L. Wong, IU. Rehman; Structural and In-vitro Adhesion Analysis of a Novel Covalently-Coupled Bioactive Composite, Journal of Biomedical Materials Research Part B: Applied Biomaterials, volume 100B, issue 1, pages, 239-48; (2012) 2. Wang, M., Joseph, R., Bonfield, W., Hydroxyapatite-polyethylene composites for bone substitution: effects of ceramic particle size and morphology, Biomaterials, 19, 2357 (1998). 3. Hench, L. L., Future developments and applications of biomaterials: an overview, Biomaterial Medical Devices Artificial Organs, , 7, 339 (1979) 4. De Scheerder, I. K., Wilczek, K. L., Verbeken, E. V., Vandorpe, J., Lan, P. N., Schacht, E., Piessens, J., De Geest, H., Biocompatibility of biodegradable and nonbiodegradable polymer-coated stents implanted in porcine peripheral arteries. Cardiovascular & Interventional Radiology, 18, 227, (1995) 5. Darr J. A. and Rehman, I., A Process for the Preparation of Carbonated Biomedical Materials”, [Abonetics Ltd.], International Patent [WO 01/83367] (2001). 6. Phillips M. J., Darr J. A., Luklinska, Z. B. and Rehman I., Synthesis and Characterisation of Nano-Biomaterials with Potential Osteological Applications, J. Mater. Sci. : Mater. In Medicine., 14, 1- 8 (2003) 7. A Asif, R Nazir, T Riaz, N Ashraf, S Zahid, R Shahid, A Ur-Rehman, AA Chaudhry, IU Rehman; Influence of processing parameters and solid concentration on microstructural properties of gel-casted porous hydroxyapatite; Journal of Porous Materials; Volume 21(1): pages; 31-37 (2014) 8. IU. Rehman, AS. Khan, (Book Chapter); Dental Regeneration. In: “Electro-spinning for Tissue Regeneration” ISBN 1 84569 741 3 Woodhead Publishing Limited, Cambridge, UK (2011) 9. SB. Qasim, RM. Delaine-Smith, T. Fey, A. Rawlinson, and IU Rehman; Freeze gelated porous membranes for periodontal tissue regeneration; Acta Biomaterialia; Volume 23, Pages 317–328, DOI: http://dx.doi.org/10.1016/j.actbio.2015.05.001 (2015)