Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Research Article

Polyhedral Oligomeric Silsesquioxane /Platelets Rich Plasma/Gelrite-Based Hydrogel Scaffold for Bone Tissue Engineering

Author(s): Saeedeh Ahmadipour, Jaleh Varshosaz*, Batool Hashemibeni, Leila Safaeian and Maziar Manshaei

Volume 26, Issue 26, 2020

Page: [3147 - 3160] Pages: 14

DOI: 10.2174/1381612826666200311124732

Price: $65

Abstract

Background: Polyhedral oligomeric silsesquioxane (POSS) is a monomer with silicon structure and an internal nanometric cage.

Objective: The purpose of this study was to provide an injectable hydrogel that could be easily located in open or closed bone fractures and injuries, and also to reduce the possible risks of infections caused by bone graft either as an allograft or an autograft.

Methods: Various formulations of temperature sensitive hydrogels containing hydroxyapatite, Gelrite, POSS and platelets rich plasma (PRP), such as the co-gelling agent and cell growth enhancer, were prepared. The hydrogels were characterized for their injectability, gelation time, phase transition temperature and viscosity. Other physical properties of the optimized formulation including compressive stress, compressive strain and Young’s modulus as mechanical properties, as well as storage and loss modulus, swelling ratio, biodegradation behavior and cell toxicity as rheometrical parameters were studied on human osteoblast MG-63 cells. Alizarin red tests were conducted to study the qualitative and quantitative osteogenic capability of the designed scaffold, and the cell adhesion to the scaffold was visualized by scanning electron microscopy.

Results: The results demonstrated that the hydrogel scaffold mechanical force and injectability were 3.34±0.44 Mpa and 12.57 N, respectively. Moreover, the scaffold showed higher calcium granules production in alizarin red staining compared to the control group. The proliferation of the cells in G4.5H1P0.03PRP10 formulation was significantly higher than in other formulations (p<0.05).

Conclusion: The optimized Gelrite/Hydroxyapatite/POSS/PRP hydrogel scaffold has useful impacts on osteoblasts activity, and may be beneficial for local drug delivery in complications including a break or bone loss.

Keywords: Polyhedral oligomeric silsesquioxane, platelets rich plasma, hydroxyapatite, gelrite, scaffold, hydrogel, bone tissue engineering, drug delivery.

« Previous Next »
[1]
Ghosh M, Halperin-Sternfeld M, Grinberg I, Adler-Abramovich L. Injectable alginate-peptide composite hydrogel as a scaffold for bone tissue regeneration. Nanomaterials (Basel) 2019; 9(4): 497.
[http://dx.doi.org/10.3390/nano9040497] [PMID: 30939729]
[2]
Götz C, Warnke PH, Kolk A. Current and future options of regeneration methods and reconstructive surgery of the facial skeleton. Oral Surg Oral Med Oral Pathol Oral Radiol 2015; 120(3): 315-23.
[http://dx.doi.org/10.1016/j.oooo.2015.05.022] [PMID: 26297391]
[3]
Bai X, Gao M, Syed S, Zhuang J, Xu X, Zhang XQ. Bioactive hydrogels for bone regeneration. Bioact Mater 2018; 3(4): 401-17.
[http://dx.doi.org/10.1016/j.bioactmat.2018.05.006] [PMID: 30003179]
[4]
Velasco MA, Narváez-Tovar CA, Garzón-Alvarado DA. Design, materials, and mechanobiology of biodegradable scaffolds for bone tissue engineering. BioMed Res Int 2015; 2015729076
[http://dx.doi.org/10.1155/2015/729076] [PMID: 25883972]
[5]
National Osteoporosis Foundation Available from:. www.nof.org
[6]
Agarwal R, García AJ. Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair. Adv Drug Deliv Rev 2015; 94: 53-62.
[http://dx.doi.org/10.1016/j.addr.2015.03.013] [PMID: 25861724]
[7]
Edri R, Gal I, Noor N, et al. Personalized hydrogels for engineering diverse fully autologous tissue implants. Adv Mater 2019; 31(1)e1803895
[http://dx.doi.org/10.1002/adma.201803895] [PMID: 30406960]
[8]
Saunders L, Ma PX. Self‐healing supramolecular hydrogels for tissue engineering applications. Macromol Biosci 2019; 19(1)e1800313
[http://dx.doi.org/10.1002/mabi.201800313] [PMID: 30565872]
[9]
Ren B, Chen X, Du S, et al. Injectable polysaccharide hydrogel embedded with hydroxyapatite and calcium carbonate for drug delivery and bone tissue engineering. Int J Biol Macromol 2018; 118(Pt A): 1257-66.
[http://dx.doi.org//10.1016/j.ijbiomac.2018.06.200] [PMID: 30021396]
[10]
Fan M, Ma Y, Tan H, et al. Covalent and injectable chitosan-chondroitin sulfate hydrogels embedded with chitosan microspheres for drug delivery and tissue engineering. Mater Sci Eng C 2017; 71: 67-74.
[http://dx.doi.org/10.1016/j.msec.2016.09.068] [PMID: 27987759]
[11]
Douglas TEL, Schietse J, Zima A, et al. Novel self-gelling injectable hydrogel/alpha-tricalcium phosphate composites for bone regeneration: Physiochemical and microcomputer tomographical characterization. J Biomed Mater Res A 2018; 106(3): 822-8.
[http://dx.doi.org/10.1002/jbm.a.36277] [PMID: 29057619]
[12]
Lopez-Heredia MA, Łapa A, Mendes AC, et al. Bioinspired, biomimetic, double-enzymatic mineralization of hydrogels for bone regeneration with calcium carbonate. Mater Lett 2017; 190: 13-6.
[http://dx.doi.org/10.1016/j.matlet.2016.12.122]
[13]
Yan J, Miao Y, Tan H, et al. Injectable alginate/hydroxyapatite gel scaffold combined with gelatin microspheres for drug delivery and bone tissue engineering. Mater Sci Eng C 2016; 63: 274-84.
[http://dx.doi.org/10.1016/j.msec.2016.02.071] [PMID: 27040220]
[14]
Agrawal K, Singh G, Puri D, Prakash S. Synthesis and characterization of hydroxyapatite powder by sol-gel method for biomedical application. J Miner Mater Charact Eng 2011; 10: 727.
[http://dx.doi.org/10.4236/jmmce.2011.108057]
[15]
Yan S, Wang T, Feng L, et al. Injectable in situ self-cross-linking hydrogels based on poly(L-glutamic acid) and alginate for cartilage tissue engineering. Biomacromolecules 2014; 15(12): 4495-508.
[http://dx.doi.org/10.1021/bm501313t] [PMID: 25279766]
[16]
Tan H, Marra KG. Injectable, biodegradable hydrogels for tissue engineering applications. Materials (Basel) 2010; 3: 1746-67.
[http://dx.doi.org/10.3390/ma3031746]
[17]
Tan H, Shen Q, Jia X, Yuan Z, Xiong D. Injectable nanohybrid scaffold for biopharmaceuticals delivery and soft tissue engineering. Macromol Rapid Commun 2012; 33(23): 2015-22.
[http://dx.doi.org/10.1002/marc.201200360] [PMID: 22941907]
[18]
Drury JL, Mooney DJ. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 2003; 24(24): 4337-51.
[http://dx.doi.org/10.1016/S0142-9612(03)00340-5] [PMID: 12922147]
[19]
Costa L, Silva-Correia J, Oliveira JM, Reis RL. Gellan Gum-based hydrogels for osteochondral repair. Adv Exp Med Biol 2018; 1058: 281-304.
[http://dx.doi.org/10.1007/978-3-319-76711-6_13] [PMID: 29691827]
[20]
Cheng K, Weng W, Han G, et al. The effect of triethanolamine on the formation of sol-gel derived fluoroapatite/hydroxyapatite solid solution. Mater Chem Phys 2003; 78: 767-71.
[http://dx.doi.org/10.1016/S0254-0584(02)00425-X]
[21]
Riman RE, Suchanek WL, Byrappa K, Chen CW, Shuk P, Oakes CS. Solution synthesis of hydroxyapatite designer particulates. Solid State Ion 2002; 151: 393-402.
[http://dx.doi.org/10.1016/S0167-2738(02)00545-3]
[22]
Gong Y, Wang C, Lai RC, Su K, Zhang F, Wang DA. An improved injectable polysaccharide hydrogel: modified gellan gum for long-term cartilage regeneration in vitro. J Mater Chem C Mater 2009; 19: 1968-77.
[http://dx.doi.org/10.1039/b818090c]
[23]
Stevens LR, Gilmore KJ, Wallace GG, In Het Panhuis M. Tissue engineering with gellan gum. Biomater Sci 2016; 4(9): 1276-90.
[http://dx.doi.org/10.1039/C6BM00322B] [PMID: 27426524]
[24]
Vieira S, da Silva Morais A, Garet E, et al. Self-mineralizing Ca-enriched methacrylated gellan gum beads for bone tissue engineering. Acta Biomater 2019; 93: 74-85.
[http://dx.doi.org/10.1016/j.actbio.2019.01.053] [PMID: 30708066]
[25]
S Nobile L, Di Trapani . Gelrite for tissue engineering applications: A mini review. Biomed J Sci& Tech Res 2018; 7: 2018.
[26]
Camargo PH, Satyanarayana KG, Wypych F. Nanocomposites: synthesis, structure, properties and new application opportunities. Mater Res 2009; 12: 1-39.
[http://dx.doi.org/10.1590/S1516-14392009000100002]
[27]
Alexander B. Morgan, Charles A Wilkie Flame retardant polymer nanocomposites 2007.
[28]
Lagashetty A, Venkataraman A. Polymer nanocomposites. Resonance 2005; 10: 49-57.
[http://dx.doi.org/10.1007/BF02867106]
[29]
Balazs AC, Emrick T, Russell TP. Nanoparticle polymer composites: where two small worlds meet. Science 2006; 314(5802): 1107-10.
[http://dx.doi.org/10.1126/science.1130557] [PMID: 17110567]
[30]
Ayandele E, Sarkar B, Alexandridis P. Polyhedral oligomeric silsesquioxane (POSS)-containing polymer nanocomposites. Nanomaterials (Basel) 2012; 2(4): 445-75.
[http://dx.doi.org/10.3390/nano2040445] [PMID: 28348318]
[31]
Wang K, Cai L, Wang S. Methacryl-polyhedral oligomeric silsesquioxane as a crosslinker for expediting photo-crosslinking of Poly (propylene fumarate): Material properties and bone cell behavior. Polymer (Guildf) 2011; 52: 2827-39.
[http://dx.doi.org/10.1016/j.polymer.2011.04.048]
[32]
Iyer P, Iyer G, Coleman M. Gas transport properties of polyimide–POSS nanocomposites. J Membr Sci 2010; 358: 26-32.
[http://dx.doi.org/10.1016/j.memsci.2010.04.023]
[33]
Iyer P, Mapkar JA, Coleman MR. A hybrid functional nanomaterial: POSS functionalized carbon nanofiber. Nanotechnology 2009; 20(32)325603
[http://dx.doi.org/10.1088/0957-4484/20/32/325603] [PMID: 19620756]
[34]
Wu J, Mather PT. POSS polymers: physical properties and biomaterials applications. Polym Rev (Phila Pa) 2009; 49: 25-63.
[http://dx.doi.org/10.1080/15583720802656237]
[35]
Li G, Pittman CU Jr. Polyhedral oligomeric silsesquioxane (POSS) polymers, copolymers, and resin nanocomposites. Macromolecules Containing Metal and MetalLike Elements: Group IVA Polymers 2005; 79-131..
[36]
Fernandes G, Yang S. Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering. Bone Res 2016; 4: 16036.
[http://dx.doi.org/10.1038/boneres.2016.36] [PMID: 28018706]
[37]
Yun JH, Han SH, Choi SH, et al. Effects of bone marrow-derived mesenchymal stem cells and platelet-rich plasma on bone regeneration for osseointegration of dental implants: preliminary study in canine three-wall intrabony defects. J Biomed Mater Res B Appl Biomater 2014; 102(5): 1021-30.
[http://dx.doi.org/10.1002/jbm.b.33084] [PMID: 24307497]
[38]
Schwartz-Arad D, Levin L, Aba M. The use of platelet rich plasma (PRP) and platelet rich fibrin (PRP) extracts in dental implantology and oral surgery. Refuat Hapeh Vehashinayim (1993) 2007; 24(1): 51-55,84..
[PMID: 17615992]
[39]
Mautner K, Malanga GA, Smith J, et al. A call for a standard classification system for future biologic research: the rationale for new PRP nomenclature. PM R 2015; 7(4)(Suppl.): S53-9.
[http://dx.doi.org/10.1016/j.pmrj.2015.02.005] [PMID: 25864661]
[40]
Lazić S, Zec S, Miljević N, Milonjić S. The effect of temperature on the properties of hydroxyapatite precipitated from calcium hydroxide and phosphoric acid. Thermochim Acta 2001; 374: 13-22.
[http://dx.doi.org/10.1016/S0040-6031(01)00453-1]
[41]
Fennis JP, Stoelinga PJ, Jansen JA. Mandibular reconstruction: a clinical and radiographic animal study on the use of autogenous scaffolds and platelet-rich plasma. Int J Oral Maxillofac Surg 2002; 31(3): 281-6.
[http://dx.doi.org/10.1054/ijom.2002.0151] [PMID: 12190135]
[42]
Eslami H, Solati-Hashjin M, Tahriri M. The comparison of powder characteristics and physicochemical, mechanical and biological properties between nanostructure ceramics of hydroxyapatite and fluoridated hydroxyapatite. Mater Sci Eng C 2009; 29: 1387-98.
[http://dx.doi.org/10.1016/j.msec.2008.10.033]
[43]
Witek L, Shi Y, Smay J. Controlling calcium and phosphate ion release of 3D printed bioactive ceramic scaffolds: An in vitro study. J Adv Ceram 2017; 6: 157-64.
[http://dx.doi.org/10.1007/s40145-017-0228-2]
[44]
Xiao Y, Friis EA, Gehrke SH, Detamore MS. Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus. Tissue Eng Part B Rev 2013; 19(5): 403-12.
[http://dx.doi.org/10.1089/ten.teb.2012.0461] [PMID: 23448091]
[45]
Douglas TE, Piwowarczyk W, Pamula E, et al. Injectable self-gelling composites for bone tissue engineering based on gellan gum hydrogel enriched with different bioglasses. Biomed Mater 2014; 9(4)045014
[http://dx.doi.org/10.1088/1748-6041/9/4/045014] [PMID: 25065649]
[46]
Tan H, Wu J, Lao L, Gao C. Gelatin/chitosan/hyaluronan scaffold integrated with PLGA microspheres for cartilage tissue engineering. Acta Biomater 2009; 5(1): 328-37.
[http://dx.doi.org/10.1016/j.actbio.2008.07.030] [PMID: 18723417]
[47]
Moxon SR, Smith AM. Controlling the rheology of gellan gum hydrogels in cell culture conditions. Int J Biol Macromol 2016; 84: 79-86.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.12.007] [PMID: 26683878]
[48]
Pang YX, Bao X. Influence of temperature, ripening time and calcination on the morphology and crystallinity of hydroxyapatite nanoparticles. J Eur Ceram Soc 2003; 23: 1697-704.
[http://dx.doi.org/10.1016/S0955-2219(02)00413-2]
[49]
Posadowska U, Brzychczy-Wloch M, Pamula E. Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment. J Mater Sci Mater Med 2016; 27(1): 9.
[http://dx.doi.org/10.1007/s10856-015-5604-2] [PMID: 26621310]
[50]
Posadowska U, Brzychczy-Włoch M, Drożdż A, et al. Injectable hybrid delivery system composed of gellan gum, nanoparticles and gentamicin for the localized treatment of bone infections. Expert Opin Drug Deliv 2016; 13(5): 613-20.
[http://dx.doi.org/10.1517/17425247.2016.1146673] [PMID: 26805778]
[51]
Wang F, Li Z, Khan M, et al. Injectable, rapid gelling and highly flexible hydrogel composites as growth factor and cell carriers. Acta Biomater 2010; 6(6): 1978-91.
[http://dx.doi.org/10.1016/j.actbio.2009.12.011] [PMID: 20004745]
[52]
Kim ZH, Lee Y, Kim SM, Kim H, Yun CK, Choi YS. A composite dermal filler comprising cross-linked hyaluronic acid and human collagen for tissue reconstruction. J Microbiol Biotechnol 2015; 25(3): 399-406.
[http://dx.doi.org/10.4014/jmb.1411.11029] [PMID: 25502824]
[53]
Montufar EB, Maazouz Y, Ginebra MP. Relevance of the setting reaction to the injectability of tricalcium phosphate pastes. Acta Biomater 2013; 9(4): 6188-98.
[http://dx.doi.org/10.1016/j.actbio.2012.11.028] [PMID: 23219844]
[54]
Posadowska U, Parizek M, Filova E, et al. Injectable nanoparticle-loaded hydrogel system for local delivery of sodium alendronate. Int J Pharm 2015; 485(1-2): 31-40.
[http://dx.doi.org/10.1016/j.ijpharm.2015.03.003] [PMID: 25747455]
[55]
Fong H, Dickens SH, Flaim GM. Evaluation of dental restorative composites containing polyhedral oligomeric silsesquioxane methacrylate. Dent Mater 2005; 21(6): 520-9.
[http://dx.doi.org/10.1016/j.dental.2004.08.003] [PMID: 15904694]
[56]
Chan ER, Striolo A, McCabe C, Cummings PT, Glotzer SC. Coarse-grained force field for simulating polymer-tethered silsesquioxane self-assembly in solution. J Chem Phys 2007; 127(11)114102
[http://dx.doi.org/10.1063/1.2753493] [PMID: 17887823]
[57]
Wang X, Xuan S, Song L, Yang H, Lu H, Hu Y. Synergistic effect of POSS on mechanical properties, flammability, and thermal degradation of intumescent flame retardant polylactide composites. J Macromol Sci Phys 2012; 51: 255-68.
[http://dx.doi.org/10.1080/00222348.2011.585334]
[58]
Son SR, Sarkar SK, Nguyen-Thuy BL, et al. Platelet-rich plasma encapsulation in hyaluronic acid/gelatin-BCP hydrogel for growth factor delivery in BCP sponge scaffold for bone regeneration. J Biomater Appl 2015; 29(7): 988-1002.
[http://dx.doi.org/10.1177/0885328214551373] [PMID: 25234121]
[59]
Kane RJ, Weiss-Bilka HE, Meagher MJ, et al. Hydroxyapatite reinforced collagen scaffolds with improved architecture and mechanical properties. Acta Biomater 2015; 17: 16-25.
[http://dx.doi.org/10.1016/j.actbio.2015.01.031] [PMID: 25644451]
[60]
Sani F, Mehdipour F, Talaei-Khozani T, Sani M, Razban V. Fabrication of platelet-rich plasma/silica scaffolds for bone tissue engineering. Bioinspir Biomin Nan 2017; 7: 74-81.
[61]
Wei G, Ma PX. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. Biomaterials 2004; 25(19): 4749-57.
[http://dx.doi.org/10.1016/j.biomaterials.2003.12.005] [PMID: 15120521]
[62]
Tan H, Rubin JP, Marra KG. Direct synthesis of biodegradable polysaccharide derivative hydrogels through aqueous Diels-Alder chemistry. Macromol Rapid Commun 2011; 32(12): 905-11.
[http://dx.doi.org/10.1002/marc.201100125] [PMID: 21520481]
[63]
Tan H, Ramirez CM, Miljkovic N, Li H, Rubin JP, Marra KG. Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering. Biomaterials 2009; 30(36): 6844-53.
[http://dx.doi.org/10.1016/j.biomaterials.2009.08.058] [PMID: 19783043]
[64]
Carrasco Luna J, Bonete Lluch D, Silvestre Muñoz A, Gomar Sancho F. Growth factors release on P-PRP activeted with trombin assessment assay. Am Int J Biol 2015; 3: 33-48.
[65]
LeGeros RZ. Properties of osteoconductive biomaterials: calcium phosphates. Clin Orthop Relat Res 2002; (395): 81-98.
[http://dx.doi.org/10.1097/00003086-200202000-00009] [PMID: 11937868]
[66]
Lee M, Chen TT, Iruela-Arispe ML, Wu BM, Dunn JC. Modulation of protein delivery from modular polymer scaffolds. Biomaterials 2007; 28(10): 1862-70.
[http://dx.doi.org/10.1016/j.biomaterials.2006.12.006] [PMID: 17184836]
[67]
Das I, De G, Hupa L, Vallittu PK. Porous SiO2 nanofiber grafted novel bioactive glass-ceramic coating: A structural scaffold for uniform apatite precipitation and oriented cell proliferation on inert implant. Mater Sci Eng C 2016; 62: 206-14.
[http://dx.doi.org/10.1016/j.msec.2016.01.053] [PMID: 26952416]
[68]
Kavya KC, Jayakumar R, Nair S, Chennazhi KP. Fabrication and characterization of chitosan/gelatin/nSiO2 composite scaffold for bone tissue engineering. Int J Biol Macromol 2013; 59: 255-63.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.04.023] [PMID: 23591473]
[69]
Liu H, Shi S, Cao J, Ji L, He Y, Xi J. Preparation and evaluation of a novel bioactive glass/lysozyme/PLGA composite microsphere. Drug Dev Ind Pharm 2015; 41(3): 458-63.
[http://dx.doi.org/10.3109/03639045.2013.877485] [PMID: 24471512]
[70]
Gong Y, Wang C, Lai RC, Su K, Zhang F, Wang DA. An improved injectable polysaccharide hydrogel: modified gellan gum for long-term cartilage regeneration in vitro. J Mater Chem 2009; 19: 1968-77.
[http://dx.doi.org/10.1039/b818090c]
[71]
Gantar A, da Silva LP, Oliveira JM, et al. Nanoparticulate bioactive-glass-reinforced gellan-gum hydrogels for bone-tissue engineering. Mater Sci Eng C 2014; 43: 27-36.
[http://dx.doi.org/10.1016/j.msec.2014.06.045] [PMID: 25175184]
[72]
Pereira DR, Canadas RF, Silva-Correia J, Marques AP, Reis RL, Oliveira JM. Gellan gum-based hydrogel bilayered scaffolds for osteochondral tissue engineering. Key Eng Mater 2014; 587: 255-60.
[http://dx.doi.org/10.4028/www.scientific.net/KEM.587.255]
[73]
Weinand C, Pomerantseva I, Neville CM, et al. Hydrogel-β-TCP scaffolds and stem cells for tissue engineering bone. Bone 2006; 38(4): 555-63.
[http://dx.doi.org/10.1016/j.bone.2005.10.016] [PMID: 16376162]
[74]
Akkineni AR, Ahlfeld T, Funk A, Waske A, Lode A, Gelinsky M. Highly concentrated alginate-gellan gum composites for 3D plotting of complex tissue engineering scaffolds. Polymers (Basel) 2016; 8(5): 170.
[http://dx.doi.org/10.3390/polym8050170] [PMID: 30979263]

Rights & Permissions Print Cite
Article Metrics
34
4
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy