Synthesis and characterization of mechanically strong carboxymethyl cellulose–gelatin–hydroxyapatite nanocomposite for load-bearing orthopedic application
Source abstract
Abstract
Novel three-dimensional hybrid polymer–hydroxyapatite nanocomposites have been developed as load-bearing synthetic bone graft through in situ mineralization process, using natural polymers carboxymethyl cellulose (CMC) and gelatin (Gel) as matrix. This process is simple and does not involve any chemical cross-linker. Detailed structural and physicochemical characterization of the samples disclosed that incorporation of gelatin with CMC assists the formation of CMC-Gel polymeric network of new conformational structure through non-covalent interactions (H-bond). The formation of hydroxyapatite (HA) in this polymeric network was occurred in such a fashion that the HA serves as bridging molecule which strengthen the polymeric network more and formed a mechanically strong three-dimensional CMC-Gel-HA nanocomposite. The synthesized CMC-Gel-HA nanocomposites have compressive strength and modulus in the range of 40–86 MPa and 0.4–1.2 GPa, respectively, analogous to human cancellous as well as cortical bone. In vitro cell interaction of the synthesized nanocomposites with osteoblast-like MG-63 cells has been evaluated. Results showed that synthesized CMC-Gel-HA nanocomposite promote cells for high alkaline phosphatase activity and extracellular mineralization. Extracellular mineralization ability of nanocomposite was investigated by alizarin red staining and von Kossa staining. Biodegradable nature and bone apatite formation ability of CMC-Gel-HA nanocomposite under simulated physiological environment were investigated by different characterization processes. Results indicated that the synthesized CMC-Gel-HA nanocomposite has great potential to be used as regenerative bone graft in major load-bearing region.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Bone Tissue Engineering Materials · Orthopaedic implants and arthroplasty · Graphene and Nanomaterials Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (70)
Show source-provided references
1. Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update Injury. Int J Care Inj 36:S20–S2710.1016/j.injury.2005.07.029 ↗
2. Brydone AS, Meek D, Maclaine S (2010) Bone grafting, orthopedic biomaterials, and the clinical need for bone engineering. J Proc Inst Mech Eng H 224:1329–134310.1243/09544119JEIM770 ↗
3. Barrere F, Mahmood TA, Groot KD, van Blitterswijk CA (2008) Advanced biomaterials for skeletal tissue regeneration: instructive and smart functions. Mater Sci Eng, R 59:38–7110.1016/j.mser.2007.12.001 ↗
4. Pina S, Oliveira JM, Reis RL (2015) Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review. Adv Mater 27:1143–116910.1002/adma.201403354 ↗
5. Armentano I, Dottori M, Fortunati E, Mattioli S, Kenny JM (2010) Biodegradable polymer matrix nanocomposites for tissue engineering: a review. Polym Degrad Stab 95:2126–214610.1016/j.polymdegradstab.2010.06.007 ↗
6. Yunos DM, Bretcanu O, Boccaccini AR (2008) Polymer-bioceramic composites for tissue engineering scaffolds. J Mater Sci 43:4433–4442. doi: 10.1007/s10853-008-2552-y10.1007/s10853-008-2552-y ↗
7. Kong L, Gao Y, Lu G, Gong Y, Zhao N, Zhang X (2006) A study on the bioactivity of chitosan/nano-hydroxyapatite composite scaffolds for bone tissue engineering. Eur Polym J 42:3171–317910.1016/j.eurpolymj.2006.08.009 ↗
8. Chen J, Nan K, Yin S, Wang Y, Wu T, Zhang Q (2010) Characterization and biocompatibility of nanohybrid scaffold prepared via in situ crystallization of hydroxyapatite in chitosan matrix. Coll Surf B 81:640–64710.1016/j.colsurfb.2010.08.017 ↗
9. Yang W, Both SK, Zuo Y, Birgani ZT, Habibovic P, Li Y, Jansen JA, Yang F (2015) Biological evaluation of porous aliphatic polyurethane/hydroxyapatite composite scaffolds for bone tissue engineering. J Biomed Mater Res 103:2251–225910.1002/jbm.a.35365 ↗
10. Sun F, Zhou H, Lee J (2011) Various preparation methods of highly porous hydroxyapatite/polymer nanoscale biocomposites for bone regeneration. Acta Biomater 7:3813–382810.1016/j.actbio.2011.07.002 ↗
11. Bleek K, Taubert A (2013) New developments in polymer-controlled, bioinspired calcium phosphate mineralization from aqueous solution. Acta Biomater 9:6283–632110.1016/j.actbio.2012.12.027 ↗
12. Wegst UGK, Bai H, Saiz E, Tomsia PA, Ritchie RO (2014) Bioinspired structural materials. Nat Mater 14:23–3610.1038/nmat4089 ↗
13. Minardi S, Corradetti B, Taraballi F, Sandri M, Eps JV, Cabrera F, Weiner BK, Tampieri A, Tasciotti E (2015) Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche, for bone augmentation. Biomaterials 62:128–13710.1016/j.biomaterials.2015.05.011 ↗
14. Wells HC, Sizeland KH, Kirby N, Hawley A, Mudie S, Haverkamp RG (2015) Collagen fibril structure and strength in acellular dermal matrix materials of bovine, porcine, and human origin. ACS Biomater Sci Eng 1:1026–103810.1021/acsbiomaterials.5b00310 ↗
15. Kane RJ, Weiss BHE, Meagher MJ, Liu Y, Gargac JA, Niebur GL, Wagner DR, Roeder RK (2015) Hydroxyapatite reinforced collagen scaffolds with improved architecture and mechanical properties. Acta Biomater 17:16–2510.1016/j.actbio.2015.01.031 ↗
16. Kikuchi M, Suetsugu Y, Tanaka J, Ito S, Ichinose S, Shiniyama K, Hiraoka Y, Mandai Y, Nakatani S (1999) The biomimetic synthesis and biocompatibility of self-organized hydroxyapatite/collagen composites. Bioceram 12:393–39610.1142/9789814291064_0094 ↗
17. Chang MC, Ikoma T, Kikuchi M, Tanaka J (2002) Crosslinkage of hydroxyapatite/collagen nanocomposite using glutaraldehyde. J Mater Sci Mat Med 13:993–99710.1023/A:1019825132610 ↗
18. Pek YS, Gao S, Arshad MSM, Leck KJ, Ying JY (2008) Porous collagen-apatite nanocomposite foams as bone regeneration scaffolds. Biomaterials 29:4300–430510.1016/j.biomaterials.2008.07.030 ↗
19. Chang MC, Ko CC, Douglas WH (2003) Preparation of hydroxyapatite-gelatin nanocomposite. Biomaterials 24:2853–286210.1016/S0142-9612(03)00115-7 ↗
20. Azami M, Tavakol S, Samadikuchaksaraei A, Hashjin MS, Baheiraei N, Kamali M, Nourani MR (2012) A porous hydroxyapatite/gelatin nanocomposite scaffold for bone tissue repair: in vitro and in vivo evaluation. J Biomater Sci 23:2353–236810.1163/156856211X617713 ↗
21. Kim HW, Knowles JC, Kim HE (2005) Porous scaffolds of gelatin-hydroxyapatite nanocomposites obtained by biomimetic approach: characterization and antibiotic drug release. J Biomed Mater Res B 74:686–69810.1002/jbm.b.30236 ↗
22. Kim HW, Kim HE, Salih V (2005) Stimulation of osteoblast responses to biomimetic nanocomposites of gelatin- hydroxyapatite for tissue engineering scaffolds. Biomaterials 26:5221–523010.1016/j.biomaterials.2005.01.047 ↗
23. Serra IR, Fradique R, Vallejo MCS, Correia TR, Miguel SP, Correia IJ (2015) Production and characterization of chitosan/gelatin/β-TCP scaffolds for improved bone tissue regeneration. Mater Sci Eng, C 55:592–60410.1016/j.msec.2015.05.072 ↗
24. Sharma C, Dinda AK, Mishra NC (2012) Synthesis and characterization of glycine modified chitosan-gelatin-alginate composite scaffold for tissue engineering applications. J Biomater Tiss Eng 2:133–14210.1166/jbt.2012.1040 ↗
25. Luo Y, Lode A, Akkineni AR, Gelinsky M (2015) Concentrated gelatin/alginate composites for fabrication of predesigned scaffolds with a favorable cell response by 3D plotting. RSC Adv 5:43480–4348810.1039/C5RA04308E ↗
26. Balakrishnana B, Joshia N, Jayakrishnanb A, Banerjee R (2013) Self cross-linked oxidized alginate/gelatin hydrogel as injectable, adhesive biomimetic scaffolds for cartilage regeneration. Acta biomaterial 10:3650–366310.1016/j.actbio.2014.04.031 ↗
27. Gautam S, Chou CF, Dinda AK, Potdar PD, Mishra NC (2014) Fabrication and characterization of PCL/gelatine/chitosan ternary nanofibrous composite scaffold for tissue engineering applications. J Mater Sci 49:1076–1089. doi: 10.1007/s10853-013-7785-810.1007/s10853-013-7785-8 ↗
28. Svensson A, Nicklasson E, Herrah T, Panilaitis B, Kaplan DL, Brittberg M, Gatenhol P (2005) Bacterial cellulose as a potential scaffold for tissue engineering of cartilage. Biomaterials 26:419–43110.1016/j.biomaterials.2004.02.049 ↗
29. Brackmann C, Bodin A, Akason M, Gatenholm P, Enijder A (2010) Visualization of the cellulose biosynthesis and cell integration into cellulose scaffolds. Biomacromol 11:542–54810.1021/bm901153t ↗
30. Hutchens SA, Benson RS, Evans BR, O’Neil HM, Rawn CJ (2006) Biomimetic synthesis of calcium deficient hydroxyapatite in a natural hydrogel. Biomaterials 27:4661–467010.1016/j.biomaterials.2006.04.032 ↗
31. Lii CY, Tomasik P, Zaleska H, Liaw SC, Lai VMF (2002) Carboxymethyl cellulose-gelatin complexes. Carbohydr polym 50:19–2610.1016/S0144-8617(01)00372-1 ↗
32. Taokaew S, Seetabhawang S, Siripong P, Phisalaphong M (2013) Biosynthesis and characterization of nanocellulose-gelatin films. Materials 6:782–79410.3390/ma6030782 ↗
33. Dash R, Foston M, Ragauskas AJ (2013) Improving the mechanical and thermal properties of gelatin hydrogels cross-linked by cellulose nanowhiskers. Carbohydr Polym 91:638–64510.1016/j.carbpol.2012.08.080 ↗
34. Rokhade AP, Agnihotri SA, Patil SA, Malliarjuna NN, Kulkarni PV, Aminabhavi TM (2006) Semi-interpenetrating polymer network microspheres of gelatin and sodium carboxymethyl cellulose for controlled release of ketorolac tromethamine. Carbohydr Polym 65:243–25210.1016/j.carbpol.2006.01.013 ↗
35. Wiwatwongwana F, Khunathon Y, Rangsri W, Promma N, Pattana S (2012) Identification of shear modulus of gelatin blended with carboxymethylcellulose scaffolds using curve fitting method from compressive test. J Mater Sci Res 1:106–113
36. Isikli C, Hasirci V, Hasirci N (2012) Development of porous chitosan-gelatin/hydroxyapatite composite scaffolds for hard tissue-engineering applications. Tiss Eng Regen Med 6:135–14310.1002/term.406 ↗
37. Sadeghi D, Nazarian H, Marouf N, Aghalu F, Nojehdehyan H, Dastjerdi EV (2013) Alkaline phosphatase activity of osteoblast cells on three-dimensional chitosan gelatin/hydroxyapatite composite scaffolds. J Dent Sch 30:203–209
38. Sharma C, Dinda AK, Potdar PD, Chou CF, Mishra NC (2016) Fabrication and characterization of novel nano-biocomposite scaffold of chitosan-gelatin-alginate-hydroxyapatite for bone tissue engineering. Mater Sci Eng C 64:416–42710.1016/j.msec.2016.03.060 ↗
39. Teng SH, Liang MH, Wang P, Luo Y (2016) Biomimetic composite microspheres of collagen/chitosan/nano-hydroxyapatite: in-situ synthesis and characterization. Mater Sci Eng C 58:610–61310.1016/j.msec.2015.09.021 ↗
40. Li J, Chen Y, Yin Y, Yao F, Yao K (2007) Modulation of nano-hydroxyapatite size via formation on chitosan-gelatin network film in situ. Biomaterials 28:781–79010.1016/j.biomaterials.2006.09.042 ↗
41. Teng S, Shi J, Peng B, Chen L (2006) The effect of alginate addition on the structure and morphology of hydroxyapatite/gelatin nanocomposites. Compos Sci Technol 66:1532–153810.1016/j.compscitech.2005.11.021 ↗
42. Garai S, Sinha A (2014) Biomimetic nanocomposites of carboxymethyl cellulose-hydroxyapatite: novel three dimensional load bearing bone grafts. Coll Surf B 115:182–19010.1016/j.colsurfb.2013.11.042 ↗
43. George A, Ravindran S (2010) Protein templates in hard tissue engineering. Nano today 5:254–26610.1016/j.nantod.2010.05.005 ↗
44. Cui FZ, Li Y, Ge J (2007) Self-assembly of mineralized collagen composites. Mater Sci Eng R 57:1–2710.1016/j.mser.2007.04.001 ↗
45. Farbod K, Nejadnik MR, Jansen JA, Leeuwenburgh SCG (2014) Interactions between inorganic and organic phases in bone tissue as a source of inspiration for design of novel nanocomposites. Tiss Eng B 20:173–18810.1089/ten.teb.2013.0221 ↗
46. Pei Y, Ye D, Zhao Q, Wang X, Zhang C, Huang W, Zhang N, Liu S, Zhang L (2015) Effective promoting wound healing with cellulose/gelatin sponges constructed directly from a cellulose solution. J Mater Chem B 3:7518–752810.1039/C5TB00477B ↗
47. Kim HL, Jung GY, Yoon JH, Han JS, Park YJ, Kim DG, Zhang M, Kim DJ (2015) Preparation and characterization of nano-sized hydroxyapatite/alginate/chitosan composite scaffolds for bone tissue engineering. Mater Sci Eng C 54:20–2510.1016/j.msec.2015.04.033 ↗
48. Koupaei N, Karkhaneh A, Joupari MD (2015) Preparation and characterization of (PCL-crosslinked-PEG)/hydroxyapatite as bone tissue engineering scaffolds. J Biomed Mater Res 103:3919–392910.1002/jbm.a.35513 ↗
49. Rodriguez IA, Saxena G, Hixon KR, Sell SA, Bowlin GL (2016) In vitro characterization of MG-63 osteoblast-like cells cultured on organic-inorganic lyophilized gelatin sponges for early bone healing. J Biomed Mater Res 104:2011–201910.1002/jbm.a.35733 ↗
50. Liuyun J, Yubao L, Chendong X (2009) Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/Carboxymethyl cellulose for bone tissue engineering. J Biomed Sci 16:65–7510.1186/1423-0127-16-65 ↗
51. Liuyun J, Yubao L, Li Z, Jianguo L (2008) Preparation and properties of a novel bone repair composite: nano-hydroxyapatite/chitosan/Carboxymethyl cellulose. J Mater Sci Mater Med 19:981–98710.1007/s10856-007-3208-1 ↗
52. Zheng X, Zhou S, Xiao Y, Yu X, Feng B (2009) In situ preparation and characterization of a novel gelatin/poly(d, l-lactide)/hydroxyapatite nanocomposite. J Biomed Mater Res B 91:181–19010.1002/jbm.b.31388 ↗
53. Rajzer I, Menaszek E, Bacakova L, Rom M, Blazewicz M (2010) In vitro and in vivo studies on biocompatibility of carbon fibers. J Mater Sci Mater Med 21:2611–262210.1007/s10856-010-4108-3 ↗
54. Chen J, Zhang X, Huang C, Cai H, Hu S, Wan Q, Pei X, Wang J (2017) Osteogenic activity and antibacterial effect of porous titanium modified with metal-organic framework films. J Biomed Mater Res A 105:834–84610.1002/jbm.a.35960 ↗
55. Garai S, Sinha A (2016) Three dimensional biphasic calcium phosphate nanocomposites for loadbearing bioactive bone grafts. Mater Sci Eng C 59:375–38310.1016/j.msec.2015.10.027 ↗
56. 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-W. J Biomed Mater Res 24:721–73410.1002/jbm.820240607 ↗
57. Li J, Zhu D, Yin J, Liu Y, Yao F, Yao K, Li J, Zhu D, Yin J, Liu Y, Yao F, Yao K (2010) Formation of nano-hydroxyapatite crystal in situ in chitosan–pectin polyelectrolyte complex network. Mater Sci Eng C 30:795–80310.1016/j.msec.2010.03.011 ↗
58. Li J, Dou Y, Yang J, Yin Y, Zhang H, Yao F, Wang H, Yao K (2009) Surface characterization and biocompatibility of micro- and nano-hydroxyapatite/chitosan-gelatin networks films. Mater Sci Eng C 29:1207–121510.1016/j.msec.2008.09.038 ↗
59. Wang F, WenY Bai T (2016) The composite hydrogels of polyvinyl alcohol–gellan gum-Ca2+with improved network structure and mechanical property. Mater Sci Eng C 69:268–27510.1016/j.msec.2016.06.084 ↗
60. Tu ZC, Huang T, Wang H, Sha XM, Shi Y, Huang XQ, Man ZZ, Li DJ (2015) Physico-chemical properties of gelatin from bighead carp (Hypophthalmichthys nobilis) scales by ultrasound-assisted extraction. J Food Sci Technol 52:2166–217410.1007/s13197-013-1239-9 ↗
61. Klug HP, Alexander LE (1974) X-ray diffraction procedures: for polycrystalline and amorphous materials, 2nd edn. Wiley, New York 4:960
62. Olszta MJ, Cheng X, Jee SS, Kumar R, Kim YY, Kaufman MJ, Douglas EP, Gower LB (2007) Bone structure and formation: a new perspective. Mater Sci Eng R 58:77–11610.1016/j.mser.2007.05.001 ↗
63. Busch S, Schwarz U, Kniep R (2001) Morphogenesis and structure of human teeth in relation to biomimetically grown fluorapatite-gelatin composites. Chem Mater 13:3260–327110.1021/cm0110728 ↗
64. Murray MGS, Wang J, Ponton CB, Marquis PM (1995) An improvement in processing of hydroxyapatite ceramics. J Mater Sci 30:3061–3074. doi: 10.1007/BF0120921810.1007/BF01209218 ↗
65. Sturm EV, Colfen H (2016) Mesocrystals: structural and morphogenetic aspects. Chem Soc Rev 45:5821–583310.1039/C6CS00208K ↗
66. Hench LL (1991) Bioceramics: from concept to clinic. J Am Ceram Soc 74:1487–151010.1111/j.1151-2916.1991.tb07132.x ↗
67. Anselme K (2000) Osteoblast adhesion on biomaterials. Biomaterials 21:667–68110.1016/S0142-9612(99)00242-2 ↗
68. Shi C, Yuan W, Khan M, Li Q, Feng Y, Yao F, Zhang W (2015) Hydrophilic PCU scaffolds prepared by grafting PEGMA and immobilizing gelatin to enhance cell adhesion and proliferation. Mater Sci Eng C 50:201–20910.1016/j.msec.2015.02.015 ↗
69. Kuo ZK, Lai PL, Toh EKW, Weng CH, Tseng HW, Chang PZ, Chen CC, Cheng CM (2016) Osteogenic differentiation of preosteoblasts on a hemostatic gelatin sponge. Sci Rep 6:32884–3289610.1038/srep32884 ↗
70. Golub EE, Battaglia KB (2007) Theo role of alkaline phosphatase in mineralization. Curr Opin Orthop 18:444–44810.1097/BCO.0b013e3282630851 ↗