Abstract
Gelatin microspheres (GMs) using various concentrations of epoxypropoxy-propyl-trimethoxysilane (EPPTMS) as a crosslinking agent were prepared. Since the crosslinking agent content and manufacturing conditions are crucial factors in the characteristics of the microspheres, this study was carried out to evaluate the effect of processing variables on morphology, and in vitro behavior of GMs using acellular simulated body fluid (SBF). It was found that the best morphology was acquired in terms of both shape and uniformity for the GMs containing a certain concentration of EPPTMS (20wt%), whereas other concentrations yielded rambling spheres. The results revealed that the size of microspheres became smaller when both the oil-to-water ratio and agitation rate were increased. Moreover, the density of the crosslinking agent was also dependent on the above-mentioned factors in 20wt% EPPTMS. Different morphologies of hydroxyapatite deposits on the surface of GMs were observed after 14 days of soaking in SBF. These in vitro acellular studies were confirmed by SEM, FTIR, and XRD analyses. According to the results of UV–Vis spectroscopy, the GMs were released into the SBF solution in a time-dependent manner; however, the fastest rate of release occurred for the largest GM.
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Hench LL, Polak JM (2002) Third-generation biomedical materials. Science 295:1014–1017
Clapper JD, Pearce ME, Guymon CA, Salem AK (2008) Biotinylated biodegradable nanotemplated hydrogel networks for cell interactive applications. Biomacromolecules 9:1188–1194
Boanini E, Bigi A (2011) Biomimetic gelatin–octacalcium phosphate core–shell microspheres. J Colloid Interf Sci 362:594–599
Rajzer I (2014) Fabrication of bioactive polycaprolactone/hydroxyapatite scaffolds with final bilayer nano-/micro-fibrous structures for tissue engineering application. J Mater Sci 49:5799–5807
Costa-Pinto AR, Correlo VM, Sol PC, Bhattacharya M, Charbord P, Delorme B, Reis RL, Neves NM (2009) Osteogenic differentiation of human bone marrow mesenchymal stem cells seeded on melt based chitosan scaffolds for bone tissue engineering applications. Biomacromolecules 10:2067–2073
Babić MM, Antic KM, Jovasevic JS, Bozic VBÐ, Davidovic SZ, Filipovic JM, Tomic SL (2015) Oxaprozin/poly(2-hydroxyethyl acrylate/itaconic acid) hydrogels: morphological, thermal, swelling, drug release and antibacterial properties. J Mater Sci 50:906–922
Li J, Sun H, Sun D, Yao Y, Yao F, Yao K (2011) Biomimetic multicomponent polysaccharide/nano-hydroxyapatite composites for bone tissue engineering. Carbohydr Polym 85:885–894
Kollath VO, Chen Q, Mullens S, Luyten J, Traina K, Boccaccini AR, Cloots R (2016) Electrophoretic deposition of hydroxyapatite and hydroxyapatite–alginate on rapid prototyped 3D Ti6Al4V scaffolds. J Mater Sci 51:2338–2346
Leeuwenburgh SCG, Jo J, Jansen JA, Wang H, Tabata Y, Yamamoto M (2010) Mineralization, biodegradation, and drug release behavior of gelatin/apatite composite microspheres for bone regeneration. Biomacromolecules 11:2653–2659
Pekarek KJ, Jacob JS, Mathiowitz E (1994) Double-walled polymer microspheres for controlled drug release. Nature 367:258–260
Tomme SRV, Nostrum CFV, Dijkstra M, De Smedt SC, Hennink WE (2008) Effect of particle size and charge on the network properties of microsphere-based hydrogels. Eur J Pharm Biopharm 70:522–530
Cascone MG, Lazzeri L, Carmignani C, Zhu Z (2002) Gelatin nanoparticles produced by a simple W/O emulsion as delivery system for methotrexate. J Mater Sci Mater Med 13:523–526
Ma G, Fujiwara J, Su ZG, Omi S (2003) Synthesis and characterization of crosslinked uniform polymeric microspheres containing a polyimide prepolymer by a new emulsification process. J Polym Sci A 41:2588–2598
Ciardelli G, Gentile P, Chiono V, Mattioli-Belmonte M, Vozzi G, Barbani N, Giusti P (2010) Enzymatically crosslinked porous composite matrices for bone tissue regeneration. J Biomed Mater Res A 92:137–151
Yamamoto M, Ikada Y, Tabata Y (2001) Controlled release of growth factors based on biodegradation of gelatin hydrogel. J Biomater Sci Polym Ed 12:77–88
Yang Y, Tang H, Kowitsch A, Mader K, Hause G, Ulrich J, Groth T (2014) Novel mineralized heparin–gelatin nanoparticles for potential application in tissue engineering of bone. J Mater Sci Mater Med 25:669–680
Ross-Murphy SB (1994) Rheological characterization of polymer gels and networks. Polym Gels Netw 2:229–237
Basan H, Gümüsdereliolu M, Orbey T (2002) Diclofenac sodium releasing pH-sensitive monolithic devices. Int J Pharm 245:191–198
Kokubo T, Kushitani H, Sakka S, Kitsugi T, Yamamuro T (1990) Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W3. J Biomed Mater Res 24:721–734
Vandelli MA, Rivasi F, Guerra P, Forni F, Arletti R (2001) Gelatin microspheres cross-linked with D, L-glyceraldehyde as a potential drug delivery system: preparation, characterization, in vitro and in vivo studies. Int J Pharm 215:175–184
Praveen RB, Dorle AK, Krishna DR (1990) Albumin microsphere: effect of process variables on size distribution and in vitro release. Drug Dev Ind Pharm 16:1791–1803
Muyonga J, Cole C, Duodu K (2004) Fourier transform infrared (FTIR) spectroscopic study of acid soluble collagen and gelatin from skins and bones of young and adult Nile perch (Lates niloticus). Food Chem 86:325–332
Chao AC (2008) Preparation of porous chitosan/GPTMS hybrid membrane and its application in affinity sorption for tyrosinase purification with Agaricus bisporus. J Membr Sci 311:306–318
Liu YL, Su YH, Lai JY (2004) In situ crosslinking of chitosan and formation of chitosan–silica hybrid membranes with using γ-glycidoxypropyltrimethoxysilane as a crosslinking agent. Polym 45:6831–6837
Chernev GE, Borisova BV, Kabaivanova LV, Salvado IM (2010) Silica hybrid biomaterials containing gelatin synthesized by sol-gel method. Cent Eur J Chem 8(4):870–876
Araújo M, Miola M, Bertone E, Baldi G, Perez J, Verné E (2015) On the mechanism of apatite-induced precipitation on 45S5 glass pellets coated with a natural-derived polymer. Appl Surf Sci 353:137–149
Nezafati N, Zamanian A (2015) Effect of silane-coupling agent concentration on morphology and in vitro bioactivity of gelatin-based nanofibrous scaffolds fabricated by electrospinning method. J Biomater Tiss Eng 5(1):78–86
Bell RJ, Dean P (1970) Atomic vibrations in vitreous silica. Discuss Faraday Soc 50:55–61
Hafidz RN, Yaakob CM, Amin I, Noorfaizan A (2011) Chemical and functional properties of bovine and porcine skin gelatin. Int Food Res J 18(2):787–791
Abrusci C, Martín-González A, Del Amo A, Catalina F, Bosch P, Corrales T (2004) Chemiluminescence study of commercial type-B gelatines. J Photochem Photobiol A 163:537–546
Eckhoff DA, Sutin JDB, Clegg RM, Gratton E (2005) Optical characterization of ultrasmall si nanoparticles prepared through electrochemical dispersion of bulk Si. J Phys Chem B 109:19786–19797
Sahin S, Selek H, Ponchel G, Ercan MT (2002) Preparation, characterization and in vivo distribution of terbutaline sulfate loaded albumin microspheres. J Control Rel 82:345–358
Yin J, Han X, Cao Y, Lu C (2014) Surface wrinkling on polydimethylsiloxane microspheres via wet surface chemical oxidation. Sci Rep 4:1–8
Li X, Xie J, Yuan X, Xia Y (2008) Coating electrospun poly (ε-caprolactone) fibers with gelatin and calcium phosphate and their use as biomimetic scaffolds for bone tissue engineering. Langmuir 24:14145–14150
Tas AC, Bhaduri SB (2004) Chemical processing of CaHPO4· 2H2O. J Amer Ceram Soc 87:2195–2200
Meng ZX, Li HF, Sun ZZ, Zheng W, Zheng YF (2013) Fabrication of mineralized electrospun PLGA and PLGA/gelatin nanofibers and their potential in bone tissue engineering. Mater Sci Eng, C 33:699–706
Guo Y, Lan J, Zhang C, Cao M, Cai Q, Yang X (2015) Mineralization on polylactide/gelatin composite nanofibers using simulated body fluid containing amino acid. Appl Surf Sci 15:538–548
Ren L, Tsuru K, Hayakawa S, Osaka A (2001) Synthesis and characterization of gelatin-siloxane hybrids derived through sol-gel procedure. J Sol-Gel Sci Techn 21:115–121
Schottner G (2001) Hybrid sol-gel-derived polymers: applications of multifunctional materials. Chem Mater 13:3422–3435
Acknowledgements
The authors would like to acknowledge Iran National Science Foundation (INSF) for the financial support of this work.
Funding
This study was funded by Iran National Science Foundation (INSF) (Grant No. 94007430).
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The author Nader Nezafati has received research grant from Iran National Science Foundation.
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Farokhi, M., Nezafati, N., Heydari, M. et al. Use of epoxypropoxy-propyl-trimethoxysilane in the fabrication of bioactive gelatin microspheres using an emulsification method. J Mater Sci 51, 9356–9366 (2016). https://doi.org/10.1007/s10853-016-0182-3
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DOI: https://doi.org/10.1007/s10853-016-0182-3