Poly(propylene fumarate)/(calcium sulphate/β-tricalcium phosphate) composites: Preparation, characterization and in vitro degradation
Introduction
Poly(propylene fumarate) (PPF) is a synthetic material that has recently been explored for use as a degradable scaffold for bone tissue engineering [1]. PPF consists of repeating units that contain one unsaturated double bond, which permits covalent cross-linking, and two ester groups, which allow for hydrolysis of the polymer into the nontoxic degradation products of fumaric acid and propylene glycol [2], [3], [4]. PPF is often combined with particles of ceramic materials such as β-tricalcium phosphate (β-TCP), calcium carbonate or calcium sulphate to improve their properties [5], [6], [7], [8]. These composite materials exhibit compressive strengths from 2 to 30 MPa, which is appropriate for replacement of cancellous bone. Most importantly, the rate of degradation and mechanical behaviour of PPF composites scaffolds can be altered by varying parameters, such as the cross-linking density, the inorganic content and the molecular weight of PPF [9], [10], [11], [12].
PPF can be cross-linked by N-vinyl pyrrolidinone (NVP) [1], [12], poly(propylene fumarate)-diacrylate (PPF-DA) macromers [3], [9] and methylmethacrylate (MMA) [7]. These studies showed that decreasing the N-VP/PPF or PPF/PPF-DA ratio, or increasing the MMA content increased the compressive strength and compressive modulus and decreased the weight loss over the degradation time. Peter et al. [5] proved that increasing molecular weight led to an increase in both compressive strength and compressive modulus and a decrease in weight loss. However, a threshold molecular weight exists above which the number of cross-linked double bonds per PPF chain is independent of the chain length, and any end effects due to steric hindrances diminish, so the molecular weight of PPF does not affect the mechanical properties of the composite significantly [1]. Ceramic fillers play a crucial role in composite reinforcement, and have been utilized in degradable polymer systems as internal buffers to neutralize the local pH and inhibit any autocatalytic degradation [9], [12]. According to early in vitro studies, the time needed to reach 20% original weight ranged from near 84 days (PPF/β-TCP composite) to over 200 days (PPF/CaSO4 composite) [5], [8]. In another degradation study sodium chloride (NaCl) porogen content appeared to have the greatest effect upon physical degradation at 32 weeks. Water absorption capacity, porosity and compressive modulus were maintained at constant values following NaCl leaching in this study [13]. These investigations all demonstrated that PPF-based scaffolds can maintain their structure for 12 months.
CaSO4 and β-TCP are more biodegradable and biocompatible than PPF. A CaSO4/β-TCP composite has been prepared in our laboratory, and the rate of its degradation can be adjusted by varying its composition and sintering temperature [14]. Therefore, filling a certain size of CaSO4/β-TCP spherical granules into PPF networks not only improves the mechanical property and biocompatibility of the composite, but also makes its degradation more controllable. To our knowledge, no research work on PPF/(CaSO4/β-TCP) biomaterial has been published before.
In this study, we aimed to develop a biodegradable PPF/(CaSO4/β-TCP) composite which may be suitable for bone replacement. In the composite, the spherical CaSO4/β-TCP granules were expected to degrade faster than the surrounding PPF/NVP, leading to an increase in the porosity of the composites. The effects of different components on the handling properties and mechanical properties of this composite are also investigated. We then assessed the factors that influence PPF/(CaSO4/β-TCP) degradation. In particular, we investigate the effects of the molecular weight of PPF, the NVP/PPF ratio and the CaSO4/β-TCP molar ratio on the in vitro degradation behaviour of PPF/(CaSO4/β-TCP) composites.
Section snippets
Materials
N,N-Dimethyl-p-toluidine (DMT) was purchased from Acros Organics (New Jersey, USA). Fumaryl chloride and NVP were purchased from Shanghai Hao Chemical Co., Ltd. (Shanghai, China). BP was purchased from Shanghai Zhongli Chemical Co., Ltd. (Shanghai, China). CaSO4, Ca(NO3)2·4H2O and (NH4)2HPO4 were purchased from Bodi Chemical Co., Ltd. (Tianjin, China). Propylene glycol, potassium carbonate, sodium sulphate, NaCl, sodium dihydrogen phosphate dodecahydrate, sodium hydroxide, disodium hydrogen
Synthesis of PPF
Three different molecular weights of PPF were obtained by varying the transesterification time; the results are shown in Table 2. The number average molecular weight (Mn), weight average molecular weight (Mw) and PI of PPF increased with increasing transesterification time.
Spherical CaSO4/β-TCP granules
The phase compositions of β-TCP powder and CaSO4/β-TCP granules are shown in Fig. 1. No other phases were found in the β-TCP powder and the granules were composed of β-TCP (JCPDS 09-0169) and CaSO4 (JCPDS 86-2270). Fig. 2
Discussion
The cross-linking research results demonstrate that the components of the composite influenced its properties. The cross-linking temperature was increased by an increase in either the polymer molecular weight or the NVP/PPF ratio. It is known that a higher molecular weight creates a more viscous solution; the more viscous a polymer solution, the greater the autoacceleration of the polymerization, leading to the immediate release of heat. The content of the CaSO4/β-TCP granules increased with
Conclusions
PPF/(CaSO4/β-TCP) composite was fabricated and characterized in this study. The maximum cross-linking temperature was lower than 47 °C so would not elicit necrosis of the surrounding tissues. The mechanical values of the PPF/(CaSO4/β-TCP) composite closely approximate the values for cancellous bone substitutes, with compressive strengths of 5 MPa and compressive modulus of 50 MPa during degradation. The networks followed very complex degradation behaviour. An increase in the molecular weight of
Acknowledgements
This work was supported by National Natural Science Research Foundation under Grant No. 50273026 and Tianjin Natural Science Research Foundation under Grant No. 043803511.
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