皮膚老化最常見的特徵是法令紋、魚尾紋等皺紋出現於臉上，為了減少衰老的跡象，於臉部進行注射式植入劑手術則提供了治療臉部衰老的選擇，理想的注射式填充材料應具有生物相容性、生物降解性及低風險之過敏反應，而由於生物活性玻璃 (Bioactive glass, BG) 其優異的生物活性及可降解性，已被使用於各種臨床應用，如骨替代材料、牙科填料、藥物載體和軟組織填充劑，因此BG受到極大關注具有前景之生醫材料。
本研究先以不同前驅物濃度 (0.6M、1.2M、1.8M及2.4M) 利用噴霧乾燥法製備58S BG粉體，並選用1.8M作為BG之前驅物濃度，再以噴霧乾燥法分別利用0.5、1.0、5.0和10.0wt%之聚乙烯醇縮丁醛 (Polyvinyl butyral, PVB) 、聚乙烯吡咯烷酮 (Polyvinyl pyrrolidone, PVP) 及聚乙烯醇 (Polyvinyl alcohol, PVA) 作為黏結劑製備造粒粉體，由掃描式電子顯微鏡(Scanning electron microscope, SEM)結果顯示以PVA製備之造粒顆粒具有較佳之形貌，最終以利用0.5、1.0、5.0和10.0wt% PVA製備之BG造粒粉體於800°C持溫5小時進行熱處理以形成BG微球。

利用X光繞射儀、掃描式電子顯微鏡及能量散射光譜儀分別進行粉體的晶相分析、表面形貌觀察、粒徑尺寸分佈及化學成分的分析，此外將0.5、1.0、5.0和10.0wt% PVB、PVP及PVA配置之BG漿料各別以流變儀進行黏度測試，最後將BG微球浸泡於人體模擬體液進行體外生物活性試驗及根據ISO10993-5規範進行體外細胞毒性測試。
從SEM影像中可以觀察出以5.0wt% PVA製備的BG微球具有最均一的粒徑大小。由體外生物活性測試結果得到生物活性的高低順序為0.5 > 1.0 > 5.0 > 10.0wt% PVA所製備的BG微球。此外，在體外細胞毒性測試顯示，透過5.0及10.0wt% PVA所製備BG微球的細胞存活率可以通過生物相容性的標準(70%)，然而以0.5及1.0wt% PVA所製備之BG微球的細胞存活率則低於70%。
比較不同BG微球的生物活性及細胞毒性，在同時考慮此兩種性質分析顯示，由5.0wt% PVA製備的BG微球具有最佳表現。

As the skin ages, the most common features are nasolabial folds, crow’feet and rhytides on the face. In order to reduce the signs of aging, injectable facial fillers offer an option in the treatment of facial aging. The ideal injectable filler should be biocompatible, biodegradability, a low risk of allergic reaction. Bioactive glasses (BGs) have been received substantial attention in recent years due to their excellent bioactivity and degradability. Therefore, BGs have been used as a promising biomaterial for various clinical applications such as bone substitutes, dental fillers, drug carriers and soft tissue fillers. Binders are required in this study for granulate particles.
In the present study demonstrated that 58S BG powders were firstly prepared from 0.6M, 1.2M, 1.8M and 2.4M precursor solutions using spray drying method. After that, the BG powder prepared from 1.8M precursor solution as a primary powder was selected to granulate with 0.5, 1.0, 5.0 and 10.0wt% Polyvinyl butyral (PVB), Polyvinyl pyrrolidone (PVP), and Polyvinyl alcohol (PVA), respectively using spray drying method. From Scanning electron microscope (SEM) results showed granulated BG microspheres with PVA have better morphologies. Eventually, the granulated BG microspheres with 0.5, 1.0, 5.0 and 10.0wt% PVA heated at 800℃ for 5h.
Characterizations of phase composition, morphology, chemical composition, particle size and distribution for granulated microspheres were performed by X-ray diffractometer, Scanning electron microscope and Energy dispersive spectroscopy. In addition, the rheological properties of BG slurries treated with 0.5, 1.0, 5.0 and 10.0wt% PVB, PVP and PVA were measured by Modular compact rheometer, respectively. At last, in vitro bioactivity was examined by immersed in simulated body fluid. and in vitro cytotoxicity of the granulated BG microspheres were assessed by MTT assay based on ISO10993-5.
Firstly, from the SEM images of granulated BG microspheres could observe that the 5.0wt% PVA granulated BG microsphere possessed the most uniform particle size in all specimens. For in vitro bioactivity tests, the results showed an order of bioactivity is granulated 58S BG microspheres with 0.5 > 1.0 > 5.0 > 10.0wt% PVA . Furthermore, the in vitro cytotoxicity results revealed that cell viabilities of granulated BG microspheres with 5.0 and 10.0wt% PVA have passed through the standard of biocompatibility (70%). However, the cell viabilities of granulated BG microspheres with 0.5 and 1.0wt% PVA lower than 70%.
To compare the bioactivity and cytotoxicity of each specimen, indicating the 5.0wt% PVA granulated BG microsphere has optimal exhibition, which takes into account this two characterizations simultaneously.

[1] E.d.R.V. Baroni, M.d.L.P. Biondo-Simões, A. Auersvald, L.A. Auersvald, M.R. Montemor Netto, M.C.A.B. Ortolan, J.N. Kohler, Influence of aging on the quality of the skin of white women: the role of collagen, Acta cirurgica brasileira, 27 (2012) 736-740.
[2] https://www.plasticsurgery.org.
[3] G. Lemperle, N. Gauthier-Hazan, M. Wolters, M. Eisemann-Klein, U. Zimmermann, D.M. Duffy, Foreign body granulomas after all injectable dermal fillers: part 1. Possible causes, Plastic reconstructive surgery, 123 (2009) 1842-1863.
[4] L. Requena, C. Requena, L. Christensen, U.S. Zimmermann, H. Kutzner, L. Cerroni, Adverse reactions to injectable soft tissue fillers, Journal of the American academy of dermatology, 64 (2011) 1-34.
[5] M.A.A. Parulan, G. Sundar, J.H. Lum, U. Ramachandran, A case report on dermal filler-related periorbital granuloma formation, Orbit, 38 (2019) 169-172.
[6] B. Talei, Complications of Injectables in the Perioral Region, Facial plastic surgery, 35 (2019) 182-192.
[7] M.A. Farage, K.W. Miller, P. Elsner, H. Maibach, Characteristics of the aging skin, Advances in wound care, 2 (2013) 5-10.
[8] T. Quan, G. Fisher, Role of age-associated alterations of the dermal extracellular matrix microenvironment in human skin aging: A mini-review, Gerontology, 61 (2015) 427-434.
[9] J. Uitto, Connective tissue biochemistry of the aging dermis: age-related alterations in collagen and elastin, Dermatologic clinics, 4 (1986) 433-446.
[10] E.L. Tanzi, T.S. Alster, Side effects and complications of variable-pulsed erbium: yttrium-aluminum-garnet laser skin resurfacing: extended experience with 50 patients, Plastic reconstructive surgery, 111 (2003) 1524-1532.
[11] R.E. Ward, L.R. Sklar, D. Eisen, Surgical and Noninvasive Modalities for Scar Revision, Dermatologic clinics, 37 (2019) 375-386.
[12] P. Micheels, S. Besse, T.C. Flynn, D. Sarazin, Y. Elbaz, Superficial dermal injection of hyaluronic acid soft tissue fillers: comparative ultrasound study, Dermatologic surgery, 38 (2012) 1162-1169.
[13] A. Tezel, G.H. Fredrickson, L. Therapy, The science of hyaluronic acid dermal fillers, Journal of cosmetic, 10 (2008) 35-42.
[14] I.W. Sutherland, Novel and established applications of microbial polysaccharides, Trends in biotechnology, 16 (1998) 41-46.
[15] J.R.E. Fraser, T.C. Laurent, U. Laurent, Hyaluronan: its nature, distribution, functions and turnover, Journal of internal medicine, 242 (1997) 27-33.
[16] A. Fallacara, S. Manfredini, E. Durini, S. Vertuani, Hyaluronic acid fillers in soft tissue regeneration, Facial plastic surgery, 33 (2017) 087-096.
[17] R. Stern, Hyaluronan catabolism: a new metabolic pathway, European journal of cell biology, 83 (2004) 317-325.
[18] M. Romagnoli, M. Belmontesi, Hyaluronic acid–based fillers: theory and practice, Clinics in dermatology, 26 (2008) 123-159.
[19] J. Newman, Review of soft tissue augmentation in the face, Clinical, cosmetic investigational dermatology, 2 (2009) 141.
[20] H.E. John, R.D. Price, Perspectives in the selection of hyaluronic acid fillers for facial wrinkles and aging skin, Patient preference and adherence, 3 (2009) 225.
[21] K.L. Beasley, M.A. Weiss, R.A. Weiss, Hyaluronic acid fillers: a comprehensive review, Facial plastic surgery, 25 (2009) 086-094.
[22] J.L. Herrmann, R.K. Hoffmann, C.E. Ward, J.M. Schulman, R.C. Grekin, Biochemistry, physiology, and tissue interactions of contemporary biodegradable injectable dermal fillers, Dermatologic Surgery, 44 (2018) S19-S31.
[23] M.A. Al-Sibani, Enhancement of cross-linking efficiency of hyaluronic acid-based hydrogels cross-linked with 1, 4-butanediol diglycidyl ether, (2017).
[24] K. Edsman, L.I. Nord, Å. Öhrlund, H. Lärkner, A.H. Kenne, Gel properties of hyaluronic acid dermal fillers, Dermatologic surgery, 38 (2012) 1170-1179.
[25] S.S. Johl, R.A. Burgett, Dermal filler agents: a practical review, Current opinion in ophthalmology, 17 (2006) 471-479.
[26] N.H. Attenello, C.S. Maas, Injectable fillers: review of material and properties, Facial plastic surgery, 31 (2015) 029-034.
[27] D. Vleggaar, Facial volumetric correction with injectable poly‐l‐lactic acid, Dermatologic surgery, 31 (2005) 1511-1518.
[28] R.S. Narins, P.H. Bowman, Injectable skin fillers, Clinics in plastic surgery, 32 (2005) 151-162.
[29] S.R. Cohen, C.F. Berner, M. Busso, M.C. Gleason, D. Hamilton, R.E. Holmes, J.J. Romano, P.P. Rullan, M.P. Thaler, Z. Ubogy, ArteFill: A long-lasting injectable wrinkle filler material–Summary of the US Food and Drug Administration trials and a progress report on 4-to 5-year outcomes, Plastic reconstructive surgery, 118 (2006) 64S-76S.
[30] G. Lemperle, T.R. Knapp, N.S. Sadick, S.M. Lemperle, ArteFill® permanent injectable for soft tissue augmentation: I. Mechanism of action and injection techniques, Aesthetic plastic surgery, 34 (2010) 264-272.
[31] D. Gomes, A. Santos, G. Neves, R. Menezes, A brief review on hydroxyapatite production and use in biomedicine, Cerâmica, 65 (2019) 282-302.
[32] C.C. Coelho, R. Araújo, P.A. Quadros, S.R. Sousa, F. Monteiro, Antibacterial bone substitute of hydroxyapatite and magnesium oxide to prevent dental and orthopaedic infections, Materials science and engineering: C, 97 (2019) 529-538.
[33] S.N. Zhao, D.L. Yang, D. Wang, Y. Pu, Y. Le, J.X. Wang, J.F. Chen, Design and efficient fabrication of micro-sized clusters of hydroxyapatite nanorods for dental resin composites, Journal of materials science, 54 (2019) 3878-3892.
[34] F. Fabiano, L. Calabrese, E. Proverbio, Mechanical behavior of hydroxyapatite-based dental resin composites, Materials for biomedical engineering, Elsevier(2019), 251-295.
[35] L.F. Sukhodub, L.B. Sukhodub, O. Litsis, Y. Prylutskyy, Synthesis and characterization of hydroxyapatite-alginate nanostructured composites for the controlled drug release, Materials chemistry and physics, 217 (2018) 228-234.
[36] C.A. Rosen, J. Gartner Schmidt, R. Casiano, T.D. Anderson, F. Johnson, L. Reussner, M. Remacle, R.T. Sataloff, J. Abitbol, G. Shaw, Vocal fold augmentation with calcium hydroxylapatite (CaHA), Otolaryngology—Head and neck surgery, 136 (2007) 198-204.
[37] R. Mayer, R. Dmochowski, R. Appell, P. Sand, I. Klimberg, K. Jacoby, C. Graham, J. Snyder, V. Nitti, J. Winters, Multicenter prospective randomized 52-week trial of calcium hydroxylapatite versus bovine dermal collagen for treatment of stress urinary incontinence, Urology, 69 (2007) 876-880.
[38] G. Casabona, M.S. Sato, Calcium Hydroxylapatite to Treat the Face, Botulinum toxins, fillers and related substances, (2019) 1-21.
[39] A.L. Berlin, M. Hussain, D.J. Goldberg, Calcium hydroxylapatite filler for facial rejuvenation: a histologic and immunohistochemical analysis, Dermatologic Surgery, 34 (2008) S64-S67.
[40] C.S. Ahn, B.K. Rao, The life cycles and biological end pathways of dermal fillers, Journal of cosmetic dermatology, 13 (2014) 212-223.
[41] S.F. Dastoor, C.E. Misch, H.L. Wang, Dermal fillers for facial soft tissue augmentation, Journal of oral implantology, 33 (2007) 191-204.
[42] K. Laeschke, Biocompatibility of microparticles into soft tissue fillers, Semin cutan med surg, 23 (2004) 214-217.
[43] V.B. Morhenn, G. Lemperle, R.L. Gallo, Phagocytosis of different particulate dermal filler substances by human macrophages and skin cells, Dermatologic surgery, 28 (2002) 484-490.
[44] L.L. Hench, Bioceramics: from concept to clinic, Journal of the American ceramic society, 74 (1991) 1487-1510.
[45] L.L. Hench, R.J. Splinter, W. Allen, T. Greenlee, Bonding mechanisms at the interface of ceramic prosthetic materials, Journal of biomedical materials research, 5 (1971) 117-141.
[46] L.L. Hench, The story of Bioglass®, Journal of materials science: materials in medicine, 17 (2006) 967-978.
[47] P. Ducheyne, Bioceramics: material characteristics versus in vivo behavior, Journal of biomedical materials research, 21 (1987) 219.
[48] L. Hench, Bioactive ceramics: Theory and clinical applications, Bioceramics, Elsevier(1994), 3-14.
[49] X.V. Bui, T.H. Dang, Bioactive glass 58S prepared using an innovation sol-gel process, Processing and application of ceramics, 13 (2019) 98-103.
[50] K. Ishikawa, K. Yoshikawa, N. Okada, Size effect on the ferroelectric phase transition in PbTiO3 ultrafine particles, Physical review B, 37 (1988) 5852.
[51] D. Arcos, A. Lopez-Noriega, E. Ruiz-Hernandez, O. Terasaki, M. Vallet-Regi, Ordered mesoporous microspheres for bone grafting and drug delivery, Chemistry of materials, 21 (2009) 1000-1009.
[52] P. Innocenzi, Infrared spectroscopy of sol–gel derived silica-based films: a spectra-microstructure overview, Journal of non-crystalline solids, 316 (2003) 309-319.
[53] E. Dietrich, H. Oudadesse, A. Lucas-Girot, Y. Le Gal, S. Jeanne, G. Cathelineau, Effects of Mg and Zn on the surface of doped melt-derived glass for biomaterials applications, Applied surface science, 255 (2008) 391-395.
[54] J. Ding, Y. Chen, W. Chen, L. Hu, G. Boulon, Effect of P2O5 addition on the structural and spectroscopic properties of sodium aluminosilicate glass, Chinese optics letters, 10 (2012) 071602-071602.
[55] M. Handke, M. Sitarz, M. Rokita, E. Galuskin, Vibrational spectra of phosphate–silicate biomaterials, Journal of molecular structure, 651 (2003) 39-54.
[56] B.J. Hong, S.J. Shih, Novel pore-forming agent to prepare of mesoporous bioactive glass using one-step spray pyrolysis, Ceramics international, 43 (2017) S771-S775.
[57] A. Yao, D. Wang, Q. Fu, W. Huang, M.N. Rahaman, Preparation of bioactive glasses with controllable degradation behavior and their bioactive characterization, Chinese science bulletin, 52 (2007) 272-276.
[58] R. Hill, An alternative view of the degradation of bioglass, Journal of materials science letters, 15 (1996) 1122-1125.
[59] E.M. Carlisle, Silicon: a requirement in bone formation independent of vitamin D 1, Calcified tissue international, 33 (1981) 27-34.
[60] E.M. Carlisle, Silicon: a possible factor in bone calcification, Science, 167 (1970) 279-280.
[61] J. Damen, J. Ten Cate, Silica-induced precipitation of calcium phosphate in the presence of inhibitors of hydroxyapatite formation, Journal of dental Research, 71 (1992) 453-457.
[62] S. Maeno, Y. Niki, H. Matsumoto, H. Morioka, T. Yatabe, A. Funayama, Y. Toyama, T. Taguchi, J. Tanaka, The effect of calcium ion concentration on osteoblast viability, proliferation and differentiation in monolayer and 3D culture, Biomaterials, 26 (2005) 4847-4855.
[63] M. Julien, S. Khoshniat, A. Lacreusette, M. Gatius, A. Bozec, E.F. Wagner, Y. Wittrant, M. Masson, P. Weiss, L. Beck, Phosphate‐dependent regulation of MGP in osteoblasts: Role of ERK1/2 and Fra‐1, Journal of bone and mineral research, 24 (2009) 1856-1868.
[64] H. Zhu, C. Hu, F. Zhang, X. Feng, J. Li, T. Liu, J. Chen, J. Zhang, Preparation and antibacterial property of silver-containing mesoporous 58S bioactive glass, Materials science and engineering: C, 42 (2014) 22-30.
[65] L. Ciołek, M. Biernat, Z. Jaegermann, E. Zaczyńska, A. Czarny, A. Jastrzębska, A. Olszyna, The studies of cytotoxicity and antibacterial activity of composites with ZnO‐doped bioglass, International journal of applied ceramic technology, 16 (2019) 541-551.
[66] A. Hadush Tesfay, Y.J. Chou, C.Y. Tan, F. Fufa Bakare, N.T. Tsou, E.W. Huang, S.J. Shih, Control of dopant distribution in yttrium-doped bioactive glass for selective internal radiotherapy applications using spray pyrolysis, Materials, 12 (2019) 986.
[67] A. Moghanian, S. Firoozi, M. Tahriri, Characterization, in vitro bioactivity and biological studies of sol-gel synthesized SrO substituted 58S bioactive glass, Ceramics international, 43 (2017) 14880-14890.
[68] H. Bakht Khosh Hagh, F. Farshi Azhar, Reinforcing materials for polymeric tissue engineering scaffolds: A review, Journal of biomedical materials research part B: Applied biomaterials, 107 (2019) 1560-1575.
[69] A. Kirsten, A. Hausmann, M. Weber, J. Fischer, H. Fischer, Bioactive and thermally compatible glass coating on zirconia dental implants, Journal of dental research, 94 (2015) 297-303.
[70] L.L. Hench, I.D. Xynos, J.M. Polak, Bioactive glasses for in situ tissue regeneration, Journal of biomaterials science, polymer edition, 15 (2004) 543-562.
[71] W. Xia, J. Chang, Well-ordered mesoporous bioactive glasses (MBG): a promising bioactive drug delivery system, Journal of controlled release, 110 (2006) 522-530.
[72] H. Li, J. He, H. Yu, C.R. Green, J. Chang, Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior, Biomaterials, 84 (2016) 64-75.
[73] M. Vallet Regí, A.J. Salinas, Ceramics as bone repair materials, Bone repair biomaterials, Elsevier(2019), 141-178.
[74] J. Liu, X. Miao, Sol–gel derived bioglass as a coating material for porous alumina scaffolds, Ceramics international, 30 (2004) 1781-1785.
[75] R. Li, A. Clark, L. Hench, An investigation of bioactive glass powders by sol‐gel processing, Journal of applied biomaterials, 2 (1991) 231-239.
[76] R. Gupta, A. Kumar, Bioactive materials for biomedical applications using sol–gel technology, Biomedical materials, 3 (2008) 034005.
[77] S.J. Shih, Y.Y. Wu, C.Y. Chen, C.-Y. Yu, Controlled morphological structure of ceria nanoparticles prepared by spray pyrolysis, Procedia engineering, 36 (2012) 186-194.
[78] S.J. Shih, L.Y.S. Chang, C.Y. Chen, K.B. Borisenko, D.J. Cockayne, Nanoscale yttrium distribution in yttrium-doped ceria powder, Journal of nanoparticle research, 11 (2009) 2145-2152.
[79] K. Masters, Scale-up of spray dryers, Drying technology, 12 (1994) 235-257.
[80] R. Patel, M. Patel, A. Suthar, Spray drying technology: an overview, Indian journal of science and technology, 2 (2009) 44-47.
[81] C. Sadek, L. Pauchard, P. Schuck, Y. Fallourd, N. Pradeau, C. Le Floch-Fouéré, R. Jeantet, Mechanical properties of milk protein skin layers after drying: Understanding the mechanisms of particle formation from whey protein isolate and native phosphocaseinate, Food hydrocolloids, 48 (2015) 8-16.
[82] P. Thybo, L. Hovgaard, J.S. Lindeløv, A. Brask, S.K. Andersen, Scaling up the spray drying process from pilot to production scale using an atomized droplet size criterion, Pharmaceutical research, 25 (2008) 1610-1620.
[83] C. Arpagaus, A. Collenberg, D. Rütti, Laboratory spray drying of materials for batteries, lasers, and bioceramics, Drying technology, 37 (2019) 426-434.
[84] T. Peng, X. Zhang, Y. Huang, Z. Zhao, Q. Liao, J. Xu, Z. Huang, J. Zhang, C.y. Wu, X. Pan, Nanoporous mannitol carrier prepared by non-organic solvent spray drying technique to enhance the aerosolization performance for dry powder inhalation, Scientific reports, 7 (2017) 46517.
[85] C. Anandharamakrishnan, Handbook of drying for dairy products, John Wiley & Sons(2017).
[86] A.S. Mujumdar, Handbook of industrial drying, CRC press(2006).
[87] J.W. Ivey, P. Bhambri, T.K. Church, D.A. Lewis, R. Vehring, Experimental investigations of particle formation from propellant and solvent droplets using a monodisperse spray dryer, Aerosol science snd technology, 52 (2018) 702-716.
[88] D. Santos, A.C. Maurício, V. Sencadas, J.D. Santos, M.H. Fernandes, P.S. Gomes, Spray Drying: An Overview, Biomaterials-Physics and Chemistry-New edition, IntechOpen(2017).
[89] L. Zhang, Y. Li, X. Li, H. Yang, X. Qiao, T. Zhou, Z. Wang, J. Zhang, D. Tang, Characterization of spray granulated Nd: YAG particles for transparent ceramics, Journal of alloys and compounds, 639 (2015) 244-251.
[90] K. Lin, D. Zhai, N. Zhang, N. Kawazoe, G. Chen, J. Chang, Fabrication and characterization of bioactive calcium silicate microspheres for drug delivery, Ceramics international, 40 (2014) 3287-3293.
[91] S. Baklouti, T. Chartier, J. Baumard, Binder distribution in spray-dried alumina agglomerates, Journal of the European ceramic society, 18 (1998) 2117-2121.
[92] A.B.D. Nandiyanto, K. Okuyama, Progress in developing spray-drying methods for the production of controlled morphology particles: From the nanometer to submicrometer size ranges, Advanced powder technology, 22 (2011) 1-19.
[93] L. Zhang, H. Yang, X. Qiao, T. Zhou, Z. Wang, J. Zhang, D. Tang, D. Shen, Q. Zhang, Systematic optimization of spray drying for YAG transparent ceramics, Journal of the European ceramic society, 35 (2015) 2391-2401.
[94] W.J. Jr Walker, J.S. Reed, S.K. Verma, Influence of slurry parameters on the characteristics of spray‐dried granules, Journal of the American ceramic society, 82 (1999) 1711-1719.
[95] E. Lintingre, F. Lequeux, L. Talini, N. Tsapis, Control of particle morphology in the spray drying of colloidal suspensions, Soft matter, 12 (2016) 7435-7444.
[96] Y. Ben, L. Zhang, S. Wei, T. Zhou, Z. Li, H. Yang, Y. Wang, F.A. Selim, C. Wong, H. Chen, PVB modified spherical granules of β-TCP by spray drying for 3D ceramic printing, Journal of alloys and compounds, 721 (2017) 312-319.
[97] S. Miyazaki, D. Nishiura, A. Shimosaka, Y. Shirakawa, J. Hidaka, Revealing the formation mechanism of granules by drying simulation of slurry droplet, Advanced powder technology, 22 (2011) 93-101.
[98] A. Stunda Zujeva, Z. Irbe, L. Berzina Cimdina, Controlling the morphology of ceramic and composite powders obtained via spray drying–a review, Ceramics international, 43 (2017) 11543-11551.
[99] H. Meyers, H. Myers, Introductory solid state physics, CRC press1997.
[100] W.H. Bragg, W.L. Bragg, The reflection of X-rays by crystals, Proceedings of the royal society of London. series A, containing papers of a mathematical and physical character, 88 (1913) 428-438.
[101] L. Spinosa, A. Ayol, Rheological characterization of sludge, Industrial and Municipal Sludge, Elsevier(2019), 225-252.
[102] A. Rigort, J.M. Plitzko, Cryo-focused-ion-beam applications in structural biology, Archives of biochemistry and biophysics, 581 (2015) 122-130.
[103] J.I. Goldstein, D.E. Newbury, J.R. Michael, N.W. Ritchie, J.H.J. Scott, D.C. Joy, Scanning electron microscopy and X-ray microanalysis, Springer(2017).
[104] T. Kokubo, H. Kushitani, S. Sakka, T. Kitsugi, T. Yamamuro, Solutions able to reproduce in vivo surface‐structure changes in bioactive glass‐ceramic A‐W3, Journal of biomedical materials research, 24 (1990) 721-734.
[105] ISO 10993-5. Biological evaluation of medical devices. Part 5: Tests for cytotoxicity: in vitro methods, The Organization Geneva, (2001).
[106] T.I. Spiridonova, S.I. Tverdokhlebov, Y.G. Anissimov, Investigation of the Size Distribution for Diffusion-Controlled Drug Release From Drug Delivery Systems of Various Geometries, Journal of pharmaceutical sciences, (2019).
[107] H. Abdi, Coefficient of variation, Encyclopedia of research design, 1 (2010) 169-171.
[108] H. Xu, Y. Wang, Y. Zheng, X. Chen, L. Ren, G. Wu, X. Huang, Preparation and characterization of bioglass/polyvinyl alcohol composite hydrogel, Biomedical materials, 2 (2007) 62.
[109] T. Gao, M. Jiang, X. Liu, G. You, W. Wang, Z. Sun, A. Ma, J. Chen, Patterned Polyvinyl Alcohol Hydrogel Dressings with Stem Cells Seeded for Wound Healing, Polymers, 11 (2019) 171.
[110] Y. Onuki, U. Bhardwaj, F. Papadimitrakopoulos, D.J. Burgess, A review of the biocompatibility of implantable devices: current challenges to overcome foreign body response, SAGE Publications, (2008).
[111] P. Sepulveda, J.R. Jones, L.L. Hench, Characterization of melt‐derived 45S5 and sol‐gel–derived 58S bioactive glasses, Journal of biomedical materials research: An official journal of the society for biomaterials, the Japanese society for biomaterials, the Australian society for biomaterials, and the Korean society for biomaterials, 58 (2001) 734-740.
[112] T. Kokubo, H. Takadama, How useful is SBF in predicting in vivo bone bioactivity?, Biomaterials, 27 (2006) 2907-2915.
[113] W. Cao, L.L. Hench, Bioactive materials, Ceramics international, 22 (1996) 493-507.
[114] J. Zhong, D. Greenspan, J. Feng, A microstructural examination of apatite induced by Bioglass® in vitro, Journal of materials mcience: materials in medicine, 13 (2002) 321-326.
[115] M. Fanovich, J.P. Lopez, Influence of temperature and additives on the microstructure and sintering behaviour of hydroxyapatites with different Ca/P ratios, Journal of materials science: materials in medicine, 9 (1998) 53-60.
[116] E. Kontonasaki, L. Papadopoulou, T. Zorba, E. Pavlidou, K. Paraskevopoulos, P. Koidis, Apatite formation on dental ceramics modified by a bioactive glass, Journal of oral rehabilitation, 30 (2003) 893-902.
[117] G. Stanciu, I. Sandulescu, B. Savu, S. Stanciu, K. Paraskevopoulos, X. Chatzistavrou, E. Kontonasaki, P. Koidis, Investigation of the hydroxyapatite growth on bioactive glass surface, Journal of biomedical and pharmaceutical engineering, 1 (2007) 34-39.
[118] C. Soundrapandian, S. Datta, B. Kundu, D. Basu, B. Sa, Porous bioactive glass scaffolds for local drug delivery in osteomyelitis: development and in vitro characterization, Aaps Pharmscitech, 11 (2010) 1675-1683.
[119] Z. Tabia, K. El Mabrouk, M. Bricha, K. Nouneh, Mesoporous bioactive glass nanoparticles doped with magnesium: drug delivery and acellular in vitro bioactivity, RSC advances, 9 (2019) 12232-12246.
[120] S.J. Shih, Y.C. Lin, L. Valentino Posma Panjaitan, D. Rahayu Meyla Sari, The correlation of surfactant concentrations on the properties of mesoporous bioactive glass, Materials, 9 (2016) 58.
[121] Y. Zhang, M. Kawasaki, K. Ando, Z. KATO, N. UCHIDA, K. Uematsu, Surface Segregation of PVA during Drying of a PVA-Water-Al2O3 Slurry, Journal of the ceramic society of Japan, 100 (1992) 1070-1073.
[122] Y. Zhang, X. Tang, N. Uchida, K. Uematsu, Binder surface segregation during spray drying of ceramic slurry, Journal of materials research, 13 (1998) 1881-1887.
[123] Y. Yang, N. Zheng, X. Wang, R. Ivone, W. Shan, J. Shen, Rapid preparation of spherical granules via the melt centrifugal atomization technique, Pharmaceutics, 11 (2019) 198.
[124] J.J. Wu, H. Wang, X. Zhu, Q. Liao, B. Ding, Centrifugal granulation performance of liquid with various viscosities for heat recovery of blast furnace slag, Applied thermal engineering, 89 (2015) 494-504.
[125] A. Frost, Rotary atomization in the ligament formation mode, Journal of agricultural engineering research, 26 (1981) 63-78.
[126] T. Breinlinger, A. Hashibon, T. Kraft, Simulation of the influence of surface tension on granule morphology during spray drying using a simple capillary force model, Powder technology, 283 (2015) 1-8.
[127] F. Iskandar, L. Gradon, K. Okuyama, Control of the morphology of nanostructured particles prepared by the spray drying of a nanoparticle sol, Journal of colloid and interface science, 265 (2003) 296-303.
[128] M. Ogino, F. Ohuchi, L.L. Hench, Compositional dependence of the formation of calcium phosphate films on bioglass, Journal of biomedical materials research, 14 (1980) 55-64.
[129] Y.J. Chou, C.W. Hsiao, N.T. Tsou, M.H. Wu, S.J. Shih, Preparation and in vitro bioactivity of micron-sized bioactive glass particles using spray drying method, Applied sciences, 9 (2019) 19.
[130] A. Yamamoto, R. Honma, M. Sumita, T. Hanawa, Cytotoxicity evaluation of ceramic particles of different sizes and shapes, Journal of biomedical materials research part A: An official journal of the society for biomaterials, the Japanese society for biomaterials, the Australian Society for Biomaterials, and the Korean society for biomaterials, 68 (2004) 244-256.
[131] P. Valerio, M.M. Pereira, A.M. Goes, M.F. Leite, The effect of ionic products from bioactive glass dissolution on osteoblast proliferation and collagen production, Biomaterials, 25 (2004) 2941-2948.
[132] J. Jones, A. Clare, Bio-glasses: an introduction, John Wiley & Sons(2012).
[133] D. Napierska, L.C. Thomassen, V. Rabolli, D. Lison, L. Gonzalez, M. Kirsch Volders, J.A. Martens, P.H. Hoet, Size‐dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells, Small, 5 (2009) 846-853.
[134] K. Takemoto, K. Matsuzaka, M. Shimono, M. Yoshinari, T. Inoue, The effect of different surface roughnesses on the differentiation of MC3T3-E1 mouse osteoblasts in vitro, Oral medicine and pathology, 15 (2011) 45-51.
[135] H. Nabeshi, T. Yoshikawa, K. Matsuyama, Y. Nakazato, A. Arimori, M. Isobe, S. Tochigi, S. Kondoh, T. Hirai, T. Akase, Size-dependent cytotoxic effects of amorphous silica nanoparticles on Langerhans cells, Die pharmazie-An international journal of pharmaceutical sciences, 65 (2010) 199-201.