Effect of hydroxyapatite on the biodegradation and biomechanical stability of polyester nanocomposites for orthopaedic applications
Introduction
In the repair of bone in orthopaedic surgery, internal fixation of fractures influences the biology of fracture healing, especially when rigid fixation using plates is performed [1]. Intramedullary nails that allow some motion and loading are usually associated with callus formation. However, plates which practically eliminate interfragmentary motion prevent external periosteal callus formation. Primary osteonal healing can occur with plate fixation but, if interfragmental gaps >1 mm exist, healing is delayed or is even impossible [1], [2], [3]. Owing to their rigid nature, metal plates induce localized bone atrophy and osteoporosis during the later stages of fracture healing (so-called “stress shielding”) [4]. Wolff proposed that, during the growth and development of trabecular bone, the bone grows and resorbs in response to the mechanical environment and thereby produces an anatomically adapted structure. However, this concept has been wrongly extended to cortical bone, with the scope that the newly formed anatomical structure is able to resist the applied stress [5]. Stress shielding interferes with blood circulation, and the weakened bone may fracture again after implant removal. Metal implants can also cause distortions in magnetic resonance imaging [6]. Metallic implants are sometimes associated with delayed hypersensitivity reactions due to metallic corrosion, the release of metal ions into the surrounding tissue and infection caused by invasion of bacteria [7]. Consequently, non-metallic bone fixation devices which can exert less stress protection on bone and allow flexible fixation of the fracture are of increasing interest [8].
The Food and Drug Administration has approved polylactide and polylactide-co-polyglycolide-based bone fixation devices (anchor system, Inion ANCHRON), PDS/PGA staple (Mitek), pins and screws (ReFIX Xtremi-T, LLC) where the required mechanical modulus is low. However, the success of polyglycolide and polylactide implants largely depends on their mechanical properties and biological lifetime. Polylactic acid (PLA) is not recommended as a bone fixation device where a higher elastic modulus is necessary. The biological lifetime depends on the degree of polymerization and crystallinity, and the control of the inflammatory process in the vicinity of the implant. PLA and polyglycolic-lactic acid (PLGA) undergo a poorly controllable “burst degradation” with liberation of acidic components, i.e., the constituting monomers and oligomers. This creates an acidic microenvironment in the vicinity of the degradation site which can damage or denature protein molecules and also dissolve the bone mineral (calcium phosphate) [9].
Hydroxyapatite (HAP), Ca10(PO4)6(OH)2 has been used in orthopaedic and dental reconstruction owing to its excellent biocompatibility and osteointegration properties [10]. However, bioactive HAP cannot be used in load-bearing applications owing to poor mechanical properties. Labella et al. prepared HAP-based composites with improved mechanical properties using 2,2 bis-4(2-hydroxy-3-methacryloyloxypropoxy) phenyl propane and a urethane dimethacrylate and silanized HAP filler for dental applications [11]. Wang et al. prepared and studied a new biomimetic composite with poly-hexamethylene adipamide and HAP filler for orthopaedic applications [12]. Bioactive HAP nanoparticles can be used as a filler for the development of nanocomposites, to get high dynamic mechanical properties using biodegradable polymers. Biodegradable nanocomposites have great application potential as orthopaedic implants [13] such as intersomatic cages for spinal arthrodesis and osteosynthetic plates in fracture healing. Generally, particulate fillers of nanoparticles tend to aggregate when the filler content becomes too high. Aggregates of nanoparticles and higher filler content in composites are responsible for local stress concentration, internal cracks and worse mechanical properties [14]. Amphiphilic molecules were used to prevent aggregation and dispersion, e.g., with carbon nanotubes dispersed in the polymeric matrix [15]. However, no improvement in the mechanical properties of nanocomposites was observed with this method, owing to plasticization of the polymeric matrix by the amphiphilic molecules.
The nanocomposites are therefore usually prepared from nanoparticles with low filler content (2%) to achieve the desired mechanical properties. However, biodegradable composites with low critical volume fraction of bioactive HAP in a composite may result in poor bone growth and remodelling. Bonfield reported that, for a HAP-reinforced high density polyethylene composite, the minimum HAP volume percentage was ∼20% for bone growth and remodelling [16]. Therefore, the ratio of filler to resin, the type of filler dispersion, the filler size and shape, the method of dispersion and the interfacial bond strength should be optimized to functional performance of the biodegradable nanocomposites.
The unsaturated polyester poly(propylene fumarate) (PPF) is a potential biodegradable polymer for orthopaedic applications. Poly(propylene fumarate-co-ethylene glycol) has been prepared and evaluated as a scaffold for the treatment of bone defects [17], [18], [19]. The present paper discusses the effect of the size and shape of HAP filler materials on the biodegradation and dynamic biomechanical stability of hydroxy-terminated high molecular weight poly(proplyene fumarate) (HT-PPFhm) thermoset nanocomposites with a high filler content for orthopaedic applications.
Section snippets
Preparation of biodegradable nanocomposites
HT-PPFhm was synthesized by refluxing and vacuum-condensation methods [20]. Briefly, 2,5-furandione and 1,2-propanediol were mixed and refluxed, followed by vacuum condensation at 140–200 °C and 1 mbar for 4 h. The reaction was catalysed by sodium acetate and tetrahydro-1,4-oxazine. The reaction product was dissolved in acetone and then washed with 25% aqueous methanol to remove any unreacted reactants. The polymer was reprecipitated in petrol ether, filtered and dried under 1 mbar using a rotary
Preparation and evaluation of nanocomposites
In order to obtain the biodegradable unsaturated polyester, HT-PPFhm, meticulous synthesis and process optimization protocols for the condensation reaction involving acid/anhydride and alcohol were adopted to avoid reverse reactions as well as side reactions at the double bonds. The present candidate polymer was obtained by esterification and isomerization of maleate. The chemical structure of the HT-PPFhm is shown in Fig. 1. The molecular weight of HT-PPFhm was 1814 g mol−1 (Mn), 2082 g mol−1 (Mw)
Summary
Biodegradable HT-PPFhm nanocomposites prepared with different HAP nanoparticles, i.e., (i) calcined HAP nanoparticles (<100 nm), (ii) precipitated HAP nanoparticles (<100 nm) and (iii) commercially available HAP nanopowder (<200 nm) (Sigma) with a filler content of 30 wt.%, exhibited different morphological and mechanical behaviour, degradation and biomechanical stability. Calcined HAP nanoparticles enabled very good crosslinking in the polymer molecule and a high crosslink density for BP3HA1
Acknowledgements
The authors (M.J., K.T.S. and M.K.M.) are grateful to the Director, Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), and Head, Biomedical Technology Wing, SCTIMST, Trivandrum, for providing support and facilities. Technical assistance by Dr. H.K. Varma, Mr. Suresh Babu, Dr. V.S. Hari Krishnan, Dr. Mira Mohanty and Dr. P.V. Mohanan is gratefully acknowledged. The authors acknowledge the financial support of the Department of Science and Technology, New Delhi, the
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