Poly(propylene fumarate)/(calcium sulphate/β-tricalcium phosphate) composites: Preparation, characterization and in vitro degradation

doi:10.1016/j.actbio.2008.09.016

Acta Biomaterialia

Volume 5, Issue 2, February 2009, Pages 628-635

https://doi.org/10.1016/j.actbio.2008.09.016 Get rights and content

Abstract

This study aimed to prepare a poly(propylene fumarate)/(calcium sulphate/β-tricalcium phosphate) (PPF/(CaSO₄/β-TCP)) composite. We first examined the effects of varying the molecular weight of PPF and the N-vinyl pyrrolidinone (NVP) to PPF ratio on the maximum cross-linking temperature and the composite compressive strength and modulus. Then the in vitro biodegradation behaviour of PPF/(CaSO₄/β-TCP) composites was investigated. The effects of varying the molecular weight of PPF, the NVP/PPF ratio and the CaSO₄/β-TCP molar ratio on the weight loss and the composite compressive strength and modulus were examined. The cross-linking temperature, which increased with increasing molecular weight of PPF and NVP/PPF ratio, ranged from 41 to 43 °C for all formulations. The mechanical properties were increased by a decrease in the NVP/PPF ratio. For all formulations, the compressive strength values fell between 12 and 62 MPa, while the compressive modulus values fell between 290 and 1149 MPa. The weight loss decreased either with increasing molecular weight of PPF or with decreasing NVP/PPF ratio and CaSO₄/β-TCP molar ratio during degradation. The compressive strength and modulus increased with decreasing NVP/PPF ratio or decreasing CaSO₄/β-TCP ratio. The greatest weight loss over 6 weeks was 14.72%. For all formulations, the compressive modulus values fell between 57 and 712 MPa and the compressive strength fell between 0.5 and 21 MPa throughout 6 weeks degradation. Scanning electron microscopy and X-ray diffraction analysis of the PPF/(CaSO₄/β-TCP) composites demonstrated that hydroxyapatite was deposited on the surface of CaSO₄/β-TCP granules during 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 (M_n), weight average molecular weight (M_w) 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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Poly(propylene fumarate)/(calcium sulphate/β-tricalcium phosphate) composites: Preparation, characterization and in vitro degradation

Abstract

Introduction

Section snippets

Materials

Synthesis of PPF

Spherical CaSO4/β-TCP granules

Discussion

Conclusions

Acknowledgements

Polymer

Biomaterials

Biomaterials

Biomaterials

Biomaterials

Crosslinking characteristics of an injectable poly(propylene fumarate)/β-tricalcium phosphate paste and mechanical properties of the crosslinked composite for use as a biodegradable bone cement

J Biomed Mater Res

Synthesis and properties of photocross-linked poly(propylene fumarate) scaffolds

J Biomater Sci Polym Ed

In vitro cytotoxicity of injectable and biodegradable poly(propylene fumarate)-based networks: unreacted macromers, cross-linked networks, and degradation products

Biomacromolecules

In vitro degradation of a poly(propylene fumarate)/β-tricalcium phosphate composite orthopaedic scaffold

Tissue Eng

In vivo degradation of a poly(propylene fumarate) biodegradable, particulate composite bone cement

Mater Res Soc Symp Proc

Ex vivo degradation of a poly(propylene glycol-fumarate) biodegradable particulate bone cement

J Biomed Mater Res

Synthesis and characterization of fumarate-based polyesters for use in bioresorbable bone cement composites

J Appl Polym Sci

Spherical CaSO₄/β-TCP granules