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Materials Letters 60 (20

Synthesis of organic–inorganic hybrid composite and its thermalconversion to porous bioactive glass monolith

Aderemi Oki ⁎, Xiangdong Qiu, Olajide Alawode, Bridget Foley

Department of Chemistry, Prairie View A&M University, Prairie View, Texas 77446, USA

Received 28 December 2005; accepted 27 January 2006Available online 17 February 2006

Abstract

We report the synthesis and bioactivity studies of 3-dimensional macro-porous material produced by thermal treatment of organic–inorganichybrid composite. This is prepared by sol–gel processing of co-poly(methylmethacrylate (MMA)-vinyltriethoxysilane (VTS)) withtetraethoxysilane (TEOS), calcium nitrate and zinc nitrate, ([CH2C(CH3)(CO2CH3)]0.8n-[CH2-CH(Si(OEt)3]0.2n-SiO2-CaO-ZnO) (1). Thermaltreatment of this polymer at 600 °C yielded macro-porous bioglass monolith, with pore size distribution between 1 and 5μm and showed excellentbone bonding ability in simulated body fluid. The ratio of VTS:MMA in the organic polymer can easily be controlled. Since the VTS is thebonding agent, the amount of VTS in the co-polymer can be utilized to increase or decrease the porosity of the hybrid composite. This may be aconvenient approach for preparation of bioglass scaffolds especially in tissue engineering of bone.© 2006 Elsevier B.V. All rights reserved.

Keywords: Composite materials; Glass; Polymers; Biomedical applications; Sol–gel preparation

1. Introduction

The regeneration of bone is a clinical issue of great interest inorthopedic and dental medicine. Autografts have the uniqueadvantage of histocompatibility without risks of diseasestransfer but suffer from its limited availability, and most oftenthe difficulty in remodeling to the desired shape required forsuccessful reconstruction [1]. Although allogenic bone graftshave unlimited availability the possibility for transmissiblepathogenic diseases and immune response dampens theenthusiasm in such procedures [2,3]. While artificial metallicimplants, for example in total hip replacement are successful forshort time solution, they lack the most basic characteristicrequired of a living tissue, ability to self repair, ability tomaintain blood supply, ability to modify structure andproperties due to environmental changes, and ability to bondto living bone [4,5].

The main goal of bone tissue engineering is to developbiodegradable materials as bone graft substitutes, especially

⁎ Corresponding author.E-mail address: Aroki@pvamu.edu (A. Oki).

0167-577X/$ - see front matter © 2006 Elsevier B.V. All rights reserved.doi:10.1016/j.matlet.2006.01.084

for filling large defects [4–8]. The ideal synthetic graft shouldpromote adequate bone regeneration at a defective site byacting as a scaffold for osseous growth, and maintainadequate strength, and be osteoconductive and degradable ata controlled rate to allow for new bone growth. Bioactiveglasses are regarded as class A biomaterials in medicalapplications [8–10]. They can bond to both bone and softtissue and can stimulate bone growth. Although bioactiveglass and ceramics have achieved great success in bonerepairs, however, their elastic modulus mismatch has limitedtheir applications to bone fillers [11]. Tissue engineeringprovides a new approach to solving this problem, where thebiomaterial is scaffold to assist or enhance the body's ownreparative capacity [12]. An ideal scaffold should be a macro-porous material that promotes cell adhesion and resorbabilityat controlled rate to match that of tissue repair. Bioglassesexhibit high osteoconductive properties and also a significantdegradability, and when prepared via sol–gel processing, theyhave interconnected mesoporous structures. However, thedifficulty seems to be finding ways of preparing macro-porous bioglass monolith. Recently, macro-porous bioglassmonoliths were prepared using sol–gel processing, andapplication of high relative humidity in the drying gel [9]

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and pore former [10]. In this study, we have prepared macro-porous sol–gel bioglass by thermal treatment of organic–inorganic hybrid prepared by sol–gel method.

2. Materials and methods

2.1. Sample preparation

All reagents used in this experiment were purchased fromAldrich (Milwaukee, USA) and used without further purifi-cation unless stated otherwise. The organic–inorganic com-posite, [CH2C(CH3)(CO2CH3)]0.8n-[CH2-CH(Si(OEt)3]0.2n-SiO2-CaO-ZnO (1), incorporating methylmethacrylate andvinyltriethoxysilane in a mole ratio of 4:1 and 1:0.5 weightratio of organic polymer to inorganic component (SiO2-CaO-ZnO) was synthesized by slight modification of the methodreported by Wei et al. [13] as follows: in-situ polymerizationof 6g (0.0315mol) of vinyltriethoxysilane and 13g (0.13mol)of methylmethacrylate monomers in 10ml of tetrahydrofuran(THF), using 0.1g (0.0006mol) of 2,2′ Azobis-isobutyroni-trile (AIBN) as free radical polymerization catalyst wascarried out in a 250ml flask. The polymerization was allowedto proceed for 10 min at 60 °C to give solution A. Theinorganic precursors with 10g (0.0408mol) of tetra-ethy-lorthosilicate (TEOS) in 10ml of ethanol, 5ml of 0.01M HCl,pre-hydrolyzed for 10min, followed by the addition of 2.0g(0.0085mol) of calcium nitrate tetra-hydrate, and 0.8g(0.0026mol) of zinc nitrate hexa-hydrate give Solution B.Solutions A and B were added together, and reacted for10 min for hydrolysis and poly-condensation, and finallytransferred into a Teflon container. Hydrolysis and poly-condensation reactions were allowed to proceed until gelation,usually within 48h. The monolithic gel formed within 48h,

Scheme

and was washed with cold methanol solution to extractunreacted organic products. The synthesis is summarized inScheme 1.

2.2. Characterization of the samples

The thermal stability of the gel monolith dried at 60 °C for48h was examined by thermo-gravimetric analysis (TGA) anddifferential scanning calorimetry (DSC) using UniversalV3.4C TA instruments TGA and DSC analyzer. The runsconsisted of a ramp at a steady rate of 5 °C/min, from 30 °Cto 800 °C. The SEM and elemental analysis of samplessubjected to thermal treatment were carried out at CornellCenter for materials Research (CCMR), at the Optical andMicroscope Facility. The electron microscope used is a JEOL8900. The EDS detector was made by Thermo-Noran usingVantage system that includes standardless EDS software forprocessing the spectra to obtain the quantitative elementalanalysis. The electron beam conditions were 15kV andseveral nanoamps. The takeoff angle is always 40°. Thetotal of the standardless analysis is always 100% due tonormalization. The area examined in each case normally wasselected at sufficient magnification to see the texture and tochoose a good area. In addition, the quantitative analysis isalso correlated with the Fourier Transform Infra RedSpectroscopy (IR 200 Thermo Nicolet).

2.3. In vitro test

Soaking in simulated body fluid (SBF) was used to test the invitro bioactivity of the composite before and after thermaltreatment. The samples were immersed in SBF with ionconcentrations nearly equal to that of human blood plasma[14] under static condition at a concentration of approximately

1.

Fig. 1. (a) FTIR of sample 1 thermally treated at 200 °C. (b) FTIR of sample 1 thermally treated at 600 °C.

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0.01g/ml of solution. The SBF was buffered to a pH of 7.25using HCl and tris (hydroxymethyl) aminomethane. Thereaction time periods were 24h, 3 day and 7 days. After eachtime period, the samples were withdrawn from the solution,washed with distilled water and dried in an oven at 110 °Covernight. SEM and FTIR were used to observe apatite layerformation on the surface.

Table 1Standardless EDS elemental analysis of composites at different after thermaltreatment

Elemental analysis 100 °C 300 °C 500 °C 600 °C

C 87.7% 80.5% 36.7% 17.5%Si 9.9% 15.5% 54.8% 66.7%Ca 1.1% 3.5% 4.7% 10.6%

3. Results and discussion

Highly porous bioactive glass monolith with satisfactoryhandling resistance is obtained by thermal treatment of theorganic–inorganic composite material. The TGA analysis of theprepared composite material shows a 20% loss in weight attemperature below 200 °C, due to the loss of solvents and volatilemolecules trapped in the gel matrix and the condensation products.Between 200 and 400 °C, the additional 45% of weight loss wasobserved, which is likely coming from the decomposition productof the organic polymer in the hybrid composite. The approximately5% weight loss above 400 °C could be attributed to thedecomposition of the residual nitrates to give NO2 and completionof conversion to glass. The DSC of the sample showed endothermicpeak at 200 °C, associated with the removal of the volatile organicproducts from condensation, and trapped solvent. The exothermicpeaks at 300 °C, and 400 °C, are associated with the decompositionof various organic compounds in the polymer, which includes thedecarboxylation of the ester groups. The final endothermic peakabove 500 °C is likely coming from the nitrate decomposition, and

the conversion to glass. The FTIR of samples thermally treated at200 °C and 600 °C is shown in Fig. 1a and b and is consistent withthe respective losses observed in the TGA.

The FTIR spectrum of the sample heated to 200 °C shows allof the major peaks for functional groups present in the hybridcomposites (the carbonyl stretching from the carboxylate (around1700cm−1), the siloxane stretches at 1080cm−1, the CH stretchesaround 2850–2950cm−1, the symmetric NO2 stretch from nitrateobserved at 1394cm−1, and NO2 asymmetric stretch at 1604cm−1,were all present), and the spectra were more defined and sharp,which may be due to the reduction in hydrogen bonding, and inagreement with the loss of solvates and volatiles observed in theTGA. After heating to 300 °C, the FTIR spectrum showed asignificant reduction in the CH stretching vibration and thecarbonyl stretching vibrations. The total disappearances of thesepeaks were observed after heating to 400 °C. In addition, a newpeak which is yet to be identified appeared at 1652cm−1 afterheating the sample above 500 °C, and we observed thedisappearance of the nitrate peak and the only other stretches that

Fig. 2. This figure shows typical SEM micrograph of the monolith after temperature treatment at 300, 500 and 600 °C.

2754 A. Oki et al. / Materials Letters 60 (2006) 2751–2755

remained are those associated with the siloxane vibrations (Fig. 1b),and the peak at 1652cm−1.

Standardless quantitative elemental analysis of the samples afterthermal treatments at 100, 300 500 and 600 °C showed a decrease incarbon contents as the temperature is increased confirming the loss ofcarbon.

It is worth noting however that the material retained about 17% Cafter it was thermally treated at 600 °C in the air (Table 1).

The results from the standardless quantitative elemental analysis aresupported by the FTIR and TGA. The presence of C after heating to600 °C temperature in air may signify that the carbon in the organic

Fig. 3. (a) SEM of 1 without thermal treatment after immersion in SBF.

polymer may have reacted with some metal to form some carbide orother compounds yet to be identified.

Fig. 2 shows typical SEM micrograph of the monolith after thermaltreatment at four different temperatures, room temperature, 300, 500and 600 °C, revealing the emergence of macro-porous network. Thelarge pores are conducive to tissue in-growth and nutrient delivery tothe site of tissue regeneration. Due to the choice of the organic polymer,the severe cracking often observed in sol–gel processed bioglass is notthe case in this highly porous monolith. Indeed, by varying the ratio ofthe two organic monomers in the co-polymer, we can easily altertextural properties and porosity.

(b) SEM of 1, thermally treated at 600 °C after immersion in SBF.

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3.1. Bioactivity assay in SBF

Fig. 3 shows the images observed by SEM of the sample with andwithout thermal treatment after immersion in SBF. The samplethermally treated at 600 °C showed spherical-shaped HA particlesaggregation on its surfaces and in the large pores within 3 days ofimmersion. The sample that is not thermally treated shows no apatiteformation, and we concluded that a large portion of the bioactive glasssurface may not be accessible to the SBF, resulting in poor activity inthe sample that is not thermally treated.

These SEM images along with the FTIR confirmed that the surfaceof thermally treated sample has been filled with HA within 3 days ofimmersion in SBF. Thermally treated samples at 300 °C show reducedapatite formation. The possible explanation for this is that the organicpolymer might be shielding the inorganic component from the SBF,and only when thermally decomposed does the inorganic componentinteracts with the SBF.

4. Conclusion

Porous bioactive glass monolith can be obtained bythermal treatment of hybrid composite of organic polymerand bioglass. The pore size distributions are large enough toallow for cell attachment and tissue in-growth. The in vitroexperiments showed that this thermally treated material hadexcellent bioactivity, with potential application in bone tissueengineering. Future work will investigate how variables suchas ratio of VTS:MMA, the ratio of polymer to bioglass, andthe addition of porosifier can be used to optimize themicrostructure and pore size distribution and the mechanicalproperties. Since the VTS is the bonding agent to theinorganic phase, the amount of VTS in the co-polymer willlikely affect the porosity of the hybrid composite before andafter thermal treatment. However, the nature of the carboncontaining residue will also be investigated.

Acknowledgement

The PIs acknowledge support from NIH-NIAMSD grant #ARI49172, and the Welch Foundation. This work made use ofthe Cornell Center for Materials Research Facilities supportedby the National Science Foundation under Award number

DMR-0520404. The PIs acknowledge financial support fromCEBC (funding EEC-0310689).

References

[1] R.F.S. Lenza, W.L. Vasconcelos, J.R. Jones, L.L. Hench, Surface modified3D scaffolds for tissue engineering, J. Mater. Sci., Mater. Med. 13 (2002)837–842.

[2] R. Heppenstall, Bone grafting in fracture treatment and healing, in: R.Heppenstall (Ed.), WB Saunders, Philadelphia, 1980, pp. 97–112.

[3] B.E. Buck, T.I. Malinin, Bone transplantation and human immunodefi-ciency virus: an estimate of risk of acquired immunodeficiency syndrome(AIDS), Clin.Orthop., 240, (1989) 129–136 14. For a review Rueger J.M.Bone replacement materials—state of the art and the way ahead.Orthopade 27, (1998) 72–79.

[4] A.G. Coombes, M.C. Meikle, Resorbable synthetic polymers as replace-ments for bone graft, Clin. Mater. 17 (1994) 35–67.

[5] S.C. Rizzi, D.J. Heath, A.G. Coombes, N. Bock, M. Textor, S. Downes,Biodegradable polymer/hydroxyapatite composites: surface analysis andinitial attachment of osteoblasts, J. Biomed. Mater. Res. 55 (2001)475–486.

[6] Ct. Laurencin, M. Attawia, M.D. Borden, Advancements in tissueengineered bone substitutes, Curr. Opin. Orthop. 10 (1999) 445–451.

[7] S.S. Kim, M.S. Park, O. Jeon, C.Y. Choi, B.S. Kim, Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering27 (2006) 1399–1409.

[8] P. Sepulveda, J.R. Jones, J. Biomed. Mater. Res. 59 (2002) 340.[9] N. Li, Q. Jie, S. Zhu, R. Wang, A new route to prepare macroporous

bioactive sol–gel glasses with high mechanical strength, Mater. Lett. 58(2004) 2747–2750.

[10] N. Li, C. Wang, S.M. Zhu, R.D.W., Preparation of macroporous sol–gelbioactive glass using polyethylene glycol as pore formers, Wuji HuaxueXuebao Bianjibu 21 (1) (2005) 95–100.

[11] L.L. Hench, J. Am. Ceram. Soc. 81 (1998) 1705.[12] S. Yang, K.F. Leong, Z. Du, C.K. Chua, The design of scaffolds for use in

tissue engineering. Part 1. Traditional factors, Tissue Eng. 7 (2001)679–689.

[13] Y. Wei, W. Wang, J.M. Yeh, B. Wang, D. Yang, J.K. Murray,Photochemical synthesis of polyacrylate-silica hybrid sol–gel materialscatalyzed by photoacids, Adv. Mater. 6 (1994) 372–374;Y. Wei, D. Jin, C. Yang, M.C. Kels, K.-Y. Qui, Organic–inorganic hybridmaterials. Relations of thermal and mechanical properties with structure,Mater. Sci. Eng. C6 (1998) 91–98.

[14] T. Kokubo, H. Kushitani, S. Sakka, T. Kitsugi, T. Yamamuro, Solutionsable to reproduce in vivo surface structure changes in bioactive glass-ceramics A-W, J. Biomed. Mater. Res. 24 (1990) 721–734.