PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS

Fatih Erdem Baştan

doi:10.18038/estubtda.674424

TR EN

PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS

Abstract

In this study, it is aimed to produce composite hydroxyapatite (HA) gelatin microspheres (HA-Gel) intended for drug delivery applications. The polymer network within the HA particle-matrix can be facilitated as a drug carrier system. The dissolution of the polymer in the physiological medium allows to release the drug in a controlled manner and also develop the cell-microsphere interactions. Gelatin functionalized HA microspheres and bare HA granules were produced by spray drying. The morphology, thermal properties, chemical and phase structure of the produced powders were analysed with SEM, TG-DTA, FTIR and XRD. HA-Gel microspheres presented spherical morphology and hollow/core-shell cross-section and included HA nanoparticles and gelatin together according to the SEM, FTIR and XRD studies. TG-DTA results showed that gelatin was evolved from the microspheres ~300 °C, and bare HA was stable up to 1400 °C. Gelatin was released from the microspheres after immersion in the phosphate buffer saline (PBS) solution for 14 days.

Keywords

Functionalized Hydroxyapatite, gelatin, spray drying

Supporting Institution

The Scientific and Technological Research Council of Turkey, TÜBİTAK

Project Number

1919B011801595

Thanks

The author would like to thank Sakarya University Thermal Spray Research and Development Laboratory, especially the head Prof. Fatih Üstel for providing the entire analyzing equipment. This work was partly supported by The Scientific and Technological Research Council of Turkey, TÜBİTAK (Project no: 1919B011801595) and the author would like to give gratitude to Mat. Eng. Hilmi Tunahan Eligül and Sergen Belit for their assistance on producing and characterization of HA/gelatin microspheres and Dr. Egemen Avcu for helping on writing process of the paper.

References

[1] Tite T, Popa A-C, Balescu LM, Bogdan IM, Pasuk I, Ferreira JMF, Stan GE. Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods. Materials 2018; 11: 2081.
[2] Siddiqui H, Pickering K, Mucalo M, Siddiqui HA, Pickering KL, Mucalo MR. A Review on the Use of Hydroxyapatite-Carbonaceous Structure Composites in Bone Replacement Materials for Strengthening Purposes. Materials 2018; 11: 1813.
[3] Safi S, Karimzadeh F, Labbaf S. Mesoporous and hollow hydroxyapatite nanostructured particles as a drug delivery vehicle for the local release of ibuprofen. Mater Sci Eng C 2018; 92: 712–719.
[4] Medeiros SJ, Oliveira AM, Carvalho JO de, Ricci R, Martins M do CC, Rodrigues BVM, Webster TJ, Viana BC, Vasconcellos LMR, Canevari RA, Marciano FR, Lobo AO. Nanohydroxyapatite/Graphene Nanoribbons Nanocomposites Induce in Vitro Osteogenesis and Promote in Vivo Bone Neoformation. ACS Biomater Sci Eng 2018; 4: 1580–1590.
[5] Diaz-Rodriguez P, Sánchez M, Landin M. Drug-Loaded Biomimetic Ceramics for Tissue Engineering. Pharmaceutics 2018; 10: 272.
[6] Bose S, Ke D, Sahasrabudhe H, Bandyopadhyay A. Additive manufacturing of biomaterials. Prog Mater Sci 2018; 93: 45–111.
[7] Özbek YY, Baştan FE, Üstel F. Synthesis and characterization of strontium-doped hydroxyapatite for biomedical applications. J Therm Anal Calorim 2016; 125: 745–750.
[8] Robles-Águila MJ, Reyes-Avendaño JA, Mendoza ME. Structural analysis of metal-doped (Mn, Fe, Co, Ni, Cu, Zn) calcium hydroxyapatite synthetized by a sol-gel microwave-assisted method. Ceram Int 2017; 43: 12705–12709.
[9] Baştan FE, Özbek YY. Producing antibacterial silver-doped hydroxyapatite powders with chemical precipitation and reshaping in a spray dryer. Mater Tehnol 2013; 47: 431–434.
[10] Lowry N, Brolly M, Han Y, McKillop S, Meenan BJ, Boyd AR. Synthesis and characterisation of nanophase hydroxyapatite co-substituted with strontium and zinc. Ceram Int 2018; 44: 7761–7770.

[11] Graziani G, Boi M, Bianchi M, Graziani G, Boi M, Bianchi M. A Review on Ionic Substitutions in Hydroxyapatite Thin Films: Towards Complete Biomimetism. Coatings 2018; 8: 269.
[12] Ratnayake JTB, Mucalo M, Dias GJ. Substituted hydroxyapatites for bone regeneration: A review of current trends. J Biomed Mater Res B Appl Biomater 2016; 105: 1285–1299.
[13] Liang C, Luo Y, Yang G, Xia D, Liu L, Zhang X, Wang H. Graphene Oxide Hybridized nHAC/PLGA Scaffolds Facilitate the Proliferation of MC3T3-E1 Cells. Nanoscale Res Lett 2018; 13: 15.
[14] Alizadeh-Osgouei M, Li Y, Wen C. A comprehensive review of biodegradable synthetic polymer-ceramic composites and their manufacture for biomedical applications. Bioact Mater 2018; 4: 22–36.
[15] Yu P, Bao R-Y, Shi X-J, Yang W, Yang M-B. Self-assembled high-strength hydroxyapatite/graphene oxide/chitosan composite hydrogel for bone tissue engineering. Carbohydr Polym 2017; 155: 507–515.
[16] Ruphuy G, Saralegi A, Lopes JC, Dias MM, Barreiro MF. Spray drying as a viable process to produce nano-hydroxyapatite/chitosan (n-HAp/CS) hybrid microparticles mimicking bone composition. Adv Powder Technol 2016; 27: 575–583.
[17] Qi C, Lin J, Fu L-H, Huang P. Calcium-based biomaterials for diagnosis, treatment, and theranostics. Chem Soc Rev 2018; 47: 357–403.
[18] Yan Y, Zhang X, Mao H, Huang Y, Ding Q, Pang X. Hydroxyapatite/gelatin functionalized graphene oxide composite coatings deposited on TiO2 nanotube by electrochemical deposition for biomedical applications. Appl Surf Sci 2015; 329: 76–82.
[19] Nair M, Nancy D, Krishnan AG, Anjusree GS, Vadukumpully S, Nair SV. Graphene oxide nanoflakes incorporated gelatin–hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells. Nanotechnology 2015; 26: 161001.
[20] Rehman MAU, Munawar MA, Schubert DW, Boccaccini AR. Electrophoretic deposition of chitosan/gelatin/bioactive glass composite coatings on 316L stainless steel: A design of experiment study. Surf Coat Technol 2019; 358: 976–986.
[21] Liu H, Cheng J, Chen F, Bai D, Shao C, Wang J, Xi P, Zeng Z. Gelatin functionalized graphene oxide for mineralization of hydroxyapatite: biomimetic and in vitro evaluation. Nanoscale 2014; 6: 5315–5322.
[22] Lian H, Zhang L, Meng Z. Biomimetic hydroxyapatite/gelatin composites for bone tissue regeneration: Fabrication, characterization, and osteogenic differentiation in vitro. Mater Des 2018; 156: 381–388.
[23] Fang C-H, Lin Y-W, Lin F-H, Sun J-S, Chao Y-H, Lin H-Y, Chang Z-C. Biomimetic Synthesis of Nanocrystalline Hydroxyapatite Composites: Therapeutic Potential and Effects on Bone Regeneration. Int J Mol Sci 2019; 20: 6002.
[24] Chen P, Liu L, Pan J, Mei J, Li C, Zheng Y. Biomimetic composite scaffold of hydroxyapatite/gelatin-chitosan core-shell nanofibers for bone tissue engineering. Mater Sci Eng C 2019; 97: 325–335.
[25] Hikmawati D, Maulida HN, Putra AP, Budiatin AS, Syahrom A. Synthesis and Characterization of Nanohydroxyapatite-Gelatin Composite with Streptomycin as Antituberculosis Injectable Bone Substitute. Int J Biomater 2019; 1–8.
[26] Bastan FE, Erdogan G, Moskalewicz T, Ustel F. Spray drying of hydroxyapatite powders: The effect of spray drying parameters and heat treatment on the particle size and morphology. J Alloys Compd 2017; 724: 586–596.
[27] Zhao S-N, Yang D-L, Wang D, Pu Y, Le Y, Wang J-X, Chen J-F. Design and efficient fabrication of micro-sized clusters of hydroxyapatite nanorods for dental resin composites. J Mater Sci 2019; 54: 3878–3892.
[28] Stipniece L, Stepanova V, Narkevica I, Salma-Ancane K, Boyd AR. Comparative study of surface properties of Mg-substituted hydroxyapatite bioceramic microspheres. J Eur Ceram Soc 2018; 38: 761–768.
[29] Yu M, Zhou K, Li Z, Zhang D. Preparation, characterization and in vitro gentamicin release of porous HA microspheres. Mater Sci Eng C 2014; 45: 306–312.
[30] Murtaza Q, Stokes J, Ardhaoui M. Experimental Analysis of Spray Dryer Used in Hydroxyapatite Thermal Spray Powder. J Therm Spray Technol 2012; 21: 963–974.
[31] Başargan T, Nasün-Saygılı G. Spray-Dried Mesoporous Hydroxyapatite–Chitosan Biocomposites. Polym-Plast Technol Eng 2015; 54: 1172–1183.
[32] Stipniece L, Salma-Ancane K, Narkevica I, Juhnevica I, Berzina-Cimdina L. Fabrication of nanostructured composites based on hydroxyapatite and ε-polylysine. Mater Lett 2016; 163: 65–68.
[33] Stipniece L, Salma-Ancane K, Rjabovs V, Juhnevica I, Turks M, Narkevica I, Berzina-Cimdina L. Development of functionalized hydroxyapatite/poly(vinyl alcohol) composites. J Cryst Growth 2016; 444: 14–20.
[34] Chang MC. Fluoride incorporation in hydroxyapatite/gelatin nanocomposite. J Mater Sci Mater Med 2008; 19: 2837–2843.
[35] Bielefeldt N, Ploska U, Berger G, Heimann L. Rapidly resorbable, temporarily mechanically stable composites for bone replacement. Key Eng Mater 2009; 396–398: 469–472.
[36] Sun R, Lu Y. Fabrication and characterization of porous hydroxyapatite microspheres by spray-drying method. Front Mater Sci China 2008; 2: 95–98.
[37] Nandiyanto ABD, Okuyama K. Progress in developing spray-drying methods for the production of controlled morphology particles: From the nanometer to submicrometer size ranges. Adv Powder Technol 2011; 22: 1–19.
[38] Ben Y, Zhang L, Wei S, Zhou T, Li Z, Yang H, Wang Y, Selim FA, Wong C, Chen H. PVB modified spherical granules of β-TCP by spray drying for 3D ceramic printing. J Alloys Compd 2017; 721: 312–319.
[39] Bertrand G, Filiatre C, Mahdjoub H, Foissy A, Coddet C. Influence of slurry characteristics on the morphology of spray-dried alumina powders. J Eur Ceram Soc 2003; 23: 263–271.
[40] Fu N, Wu WD, Wu Z, Moo FT, Woo MW, Selomulya C, Chen XD. Formation process of core-shell microparticles by solute migration during drying of homogenous composite droplets. AIChE J 2017; 63: 3297–3310.
[41] Sinha A, Mishra T, Ravishankar N. Polymer assisted hydroxyapatite microspheres suitable for biomedical application. J Mater Sci Mater Med 2008; 19: 2009–2013.
[42] Yao H-L, Hu X-Z, Bai X-B, Wang H-T, Chen Q-Y, Ji G-C. Comparative study of HA/TiO2 and HA/ZrO2 composite coatings deposited by high-velocity suspension flame spray (HVSFS). Surf Coat Technol 2018; 351: 177–187.
[43] Hidalgo-Robatto BM, López-Álvarez M, Azevedo AS, Dorado J, Serra J, Azevedo NF, González P. Pulsed laser deposition of copper and zinc doped hydroxyapatite coatings for biomedical applications. Surf Coat Technol 2018; 333: 168–177.
[44] Paul S, Pal A, Choudhury AR, Bodhak S, Balla VK, Sinha A, Das M. Effect of trace elements on the sintering effect of fish scale derived hydroxyapatite and its bioactivity. Ceram Int 2017; 43: 15678–15684.
[45] Ahlawat J, Kumar V, Gopinath P. Carica papaya loaded poly (vinyl alcohol)-gelatin nanofibrous scaffold for potential application in wound dressing. Mater Sci Eng C 2019; 103: 109834.
[46] Yin F, Lin L, Zhan S. Preparation and properties of cellulose nanocrystals, gelatin, hyaluronic acid composite hydrogel as wound dressing. J Biomater Sci Polym Ed 2019; 30: 190–201.
[47] Shu C, Xianzhu Y, Zhangyin X, Guohua X, Hong L, Kangde Y. Synthesis and sintering of nanocrystalline hydroxyapatite powders by gelatin-based precipitation method. Ceram Int 2007; 33: 193–196.
[48] Tõnsuaadu K, Gross K, Plūduma L, Veiderma M. A review on the thermal stability of calcium apatites. J Therm Anal Calorim 2012; 110: 647–659.
[49] Sofronia AM, Baies R, Anghel EM, Marinescu CA, Tanasescu S. Thermal and structural characterization of synthetic and natural nanocrystalline hydroxyapatite. Mater Sci Eng C 2014; 43: 153–163.
[50] Ran J, Hu J, Chen L, Shen X, Tong H. Preparation and characterization of gelatin/hydroxyapatite nanocomposite for bone tissue engineering. Polym Compos 2017; 38: 1579–1590.
[51] Sanoop PK, Mahesh KV, Nampoothiri KM, Mangalaraja RV, Ananthakumar S. Multifunctional ZnO-biopolymer nanocomposite coatings for health-care polymer foams and fabrics. J Appl Polym Sci 2012; 126: E233–E244.
[52] Pawlik A, Rehman MAU, Nawaz Q, Bastan FE, Sulka GD, Boccaccini AR. Fabrication and characterization of electrophoretically deposited chitosan-hydroxyapatite composite coatings on anodic titanium dioxide layers. Electrochimica Acta 2019; 307: 465–473.
[53] Wei L, Yang H, Hong J, He Z, Deng C. Synthesis and structure properties of Se and Sr co-doped hydroxyapatite and their biocompatibility. J Mater Sci 2019; 54: 2514–2525.
[54] Chao SC, Wang M-J, Pai N-S, Yen S-K. Preparation and characterization of gelatin–hydroxyapatite composite microspheres for hard tissue repair. Mater Sci Eng C 2015; 57: 113–122.
[55] Kailasanathan C, Selvakumar N. Influence of alumina reinforcement on nano-hydroxyapatite/biopolymer composite for biomedical applications. Int J Polym Anal Charact 2016; 21: 554–562.
[56] Kolmas J, Velard F, Jaguszewska A, Lemaire F, Kerdjoudj H, Gangloff SC, Kaflak A. Substitution of strontium and boron into hydroxyapatite crystals: Effect on physicochemical properties and biocompatibility with human Wharton-Jelly stem cells. Mater Sci Eng C 2017; 79: 638–646.
[57] Champion E. Sintering of calcium phosphate bioceramics. Acta Biomater 2013; 9: 5855–5875.
[58] Sirivat A, Paradee N. Facile synthesis of gelatin-coated Fe3O4 nanoparticle: Effect of pH in single-step co-precipitation for cancer drug loading. Mater Des 2019; 181: 107942.
[59] Rahmanian M, seyfoori A, Dehghan MM, Eini L, Naghib SM, Gholami H, Farzad Mohajeri S, Mamaghani KR, Majidzadeh-A K. Multifunctional gelatin–tricalcium phosphate porous nanocomposite scaffolds for tissue engineering and local drug delivery: In vitro and in vivo studies. J Taiwan Inst Chem Eng 2019; 101: 214–220.

Details

Primary Language

English

Subjects

Engineering

Journal Section

Research Article

Authors

Fatih Erdem Baştan ^*
0000-0002-9224-7742
Türkiye

Publication Date

March 26, 2021

Submission Date

January 13, 2020

Acceptance Date

February 4, 2021

Published in Issue

Year 2021 Volume: 22 Number: 1

DOI

https://doi.org/10.18038/estubtda.674424

IZ

https://izlik.org/JA67FK52DY

APA

Baştan, F. E. (2021). PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS. Eskişehir Technical University Journal of Science and Technology A - Applied Sciences and Engineering, 22(1), 10-22. https://doi.org/10.18038/estubtda.674424

AMA

1.Baştan FE. PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS. Estuscience - Se. 2021;22(1):10-22. doi:10.18038/estubtda.674424

Chicago

Baştan, Fatih Erdem. 2021. “PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS”. Eskişehir Technical University Journal of Science and Technology A - Applied Sciences and Engineering 22 (1): 10-22. https://doi.org/10.18038/estubtda.674424.

EndNote

Baştan FE (March 1, 2021) PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS. Eskişehir Technical University Journal of Science and Technology A - Applied Sciences and Engineering 22 1 10–22.

IEEE

[1]F. E. Baştan, “PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS”, Estuscience - Se, vol. 22, no. 1, pp. 10–22, Mar. 2021, doi: 10.18038/estubtda.674424.

ISNAD

Baştan, Fatih Erdem. “PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS”. Eskişehir Technical University Journal of Science and Technology A - Applied Sciences and Engineering 22/1 (March 1, 2021): 10-22. https://doi.org/10.18038/estubtda.674424.

JAMA

1.Baştan FE. PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS. Estuscience - Se. 2021;22:10–22.

MLA

Baştan, Fatih Erdem. “PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS”. Eskişehir Technical University Journal of Science and Technology A - Applied Sciences and Engineering, vol. 22, no. 1, Mar. 2021, pp. 10-22, doi:10.18038/estubtda.674424.

Vancouver

1.Fatih Erdem Baştan. PRODUCTION and CHARACTERIZATION of GELATIN FUNCTIONALIZED HYDROXYAPATITE COMPOSITE MICROSPHERES for BIOMEDICAL APPLICATIONS. Estuscience - Se. 2021 Mar. 1;22(1):10-22. doi:10.18038/estubtda.674424

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https://doi.org/10.18038/estubtda.1428785

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