固体核磁共振技术在骨基生物材料研究中的应用

doi:10.11938/cjmr20170114

摘要/Abstract

摘要： 骨是人体的结构组织之一，又是重要的造血器官，它在支持和保护体内器官、贮存钙和磷、参与人体代谢和为肌肉提供附着等方面具有重要的作用，因此了解骨的微观结构对预防和治疗骨疾病有重要意义.由于骨形态多样化，无机和有机成分共存，而且骨样品对物理和化学处理十分敏感，因此对其研究存在许多实验困难.与其他表征技术相比，固体核磁共振（NMR）检测对骨样品不需要任何处理，不会破坏其自身结构，可以实现原位检测.另外，骨头中的许多元素（¹H、¹³C、³¹P、¹⁹F、⁴³Ca、²⁹Si、²⁵Mg和⁸⁷Sr）都是NMR可观察核，因此高分辨固体NMR技术是研究骨基生物材料的强有力工具.该文综述了近年来固体NMR技术在骨基生物材料研究中的应用进展.

关键词: 生物玻璃, 固体核磁共振(solid-state NMR), 骨头, 羟基磷灰石, 生物矿化

Abstract: Bone, as a structural organization and an important hematopoietic organ of the human body, plays critical biological roles in protecting human organs, storing calcium and phosphorus, participating in metabolism regulation and providing attachment sites for muscles. Understanding the microstructure of bone is important for intervention and treatment of bone diseases. However, experimental characterizations of the bone has been hindered by the morphological diversity of the bone, coexistence of organic and inorganic components, and sensitivity of bone samples to physical and chemical treatment. Compared with other techniques, solid-state nuclear magnetic resonance (NMR) can study the bone in-situ without any chemical pretreatment, thus avoiding changing bone structure. In addition, most of the chemical elements in the bone are magnetic resonance detectable, such as ¹H, ¹³C, ³¹P, ¹⁹F, ⁴³Ca, ²⁹Si, ²⁵Mg and ⁸⁷Sr. Therefore, high resolution solid-state NMR technique provides a powerful tool for structural studies of the bone and bone biomaterials. In this paper, we reviewed the recent progresses in the application of solid-state NMR to bone and bone biomaterials studies.

Key words: bioglass, biomineralization, hydroxyapatite, solid-state NMR, bone

中图分类号:

O482.53

李东北, 许帅, 喻志武. 固体核磁共振技术在骨基生物材料研究中的应用[J]. 波谱学杂志, 2017, 34(1): 115-129.

LI Dong-bei, XU Shuai, YU Zhi-wu. Application of Solid-State NMR to Bone and Bone Biomaterials[J]. Chinese Journal of Magnetic Resonance, 2017, 34(1): 115-129.

参考文献

[1] JOHNELL O, KANIS J A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures[J]. Osteoporosis Int, 2006, 17(12):1726-1733.
[2] GULLBERG B, JOHNELL O, KANIS J A. World-wide projections for hip fracture[J]. Osteoporosis Int, 1997, 7(5):407-413.
[3] MELTON L J. Hip fractures:A worldwide problem today and tomorrow[J]. Bone, 1993, 14(S):1-8.
[4] MELTON L J, KAN S H, FRYE M A, et al. Epidemiology of vertebral fractures in women[J]. Am J Epidemiol, 1989, 129(5):1000-1011.
[5] BOCK R M, MCENTIRE B J, BAL B S, et al. Surface modulation of silicon nitride ceramics for orthopaedic applications[J]. Acta Biomater, 2015, 26:318-330.
[6] WU C, ZHANG Y, ZHU Y, et al. Structure-property relationships of silk-modified mesoporous bioglass scaffolds[J]. Biomaterials, 2010, 31(13):3429-3438.
[7] VANI R, GIRIJA E K, ELAYARAJA K, et al. Hydrothermal synthesis of porous triphasic hydroxyapatite/(alpha and beta) tricalcium phosphate[J]. J Mater Sci Mater Med, 2009, 20(S1):43-48.
[8] ZHANG Y, VENUGOPAL J R, EL-TURKI A, et al. Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering[J]. Biomaterials, 2008, 29(32):4314-4322.
[9] HUTCHENS S A, BENSON R S, EVANS B R, et al. Biomimetic synthesis of calcium-deficient hydroxyapatite in a natural hydrogel[J]. Biomaterials, 2006, 27(26):4661-4670.
[10] HU Q L, LI B Q, WANG M, et al. Preparation and characterization of biodegradable chitosan/hydroxyapatite nanocomposite rods via in situ hybridization:A potential material as internal fixation of bone fracture[J]. Biomaterials, 2004, 25(5):779-785.
[11] DUPONT L, GUILLON E, BOUANDA J, et al. EXAFS and XANES studies of retention of copper and lead by a lignocellulosic biomaterial[J]. Environ Sci Technol, 2002, 36(23):5062-5066.
[12] CHEN J, YU Z, ZHU P, et al. Effects of fluorine on the structure of fluorohydroxyapatite:A study by XRD, solid-state NMR and Raman spectroscopy[J]. J Mater Chem B, 2015, 3(1):34-38.
[13] LAURENCIN D, ALMORA-BARRIOS N, DE LEEUW N H, et al. Magnesium incorporation into hydroxyapatite[J]. Biomaterials, 2011, 32(7):1826-1837.
[14] CHEN P H, TSENG Y H, MOU Y, et al. Adsorption of a statherin peptide fragment on the surface of nanocrystallites of hydroxyapatite[J]. J Am Chem Soc, 2008, 130(9):2862-2868.
[15] XU J, ZHU P, GAN Z, et al. Natural-abundance ⁴³Ca solid-state NMR spectroscopy of bone[J]. J Am Chem Soc, 2010, 132(33):11504-11509.
[16] CHO G Y, WU Y T, ACKERMAN J L. Detection of hydroxyl ions in bone mineral by solid-state NMR spectroscopy[J]. Science, 2003, 300(5622):1123-1127.
[17] WANG Y, VON EUW S, FERNANDES F M, et al. Water-mediated structuring of bone apatite[J]. Nat Mater, 2013, 12(12):1144-1153.
[18] HU Y Y, RAWAL A, SCHMIDT-ROHR K. Strongly bound citrate stabilizes the apatite nanocrystals in bone[J]. Proc Natl Acad Sci USA, 2010, 107(52):22425-22429.
[19] BONHOMME C, GERVAIS C, FOLLIET N, et al. ⁸⁷Sr solid-state NMR as a structurally sensitive tool for the investigation of materials:Antiosteoporotic pharmaceuticals and bioactive glasses[J]. J Am Chem Soc, 2012, 134(30):12611-12628.
[20] WATTS S J, HILL R G, O'DONNELL M D, et al. Influence of magnesia on the structure and properties of bioactive glasses[J]. J Non-Cryst Solids, 2010, 356(9, 10):517-524.
[21] LAURENCIN D, WONG A, CHRZANOWSKI W, et al. Probing the calcium and sodium local environment in bones and teeth using multinuclear solid state NMR and X-ray absorption spectroscopy[J]. Phys Chem Chem Phys, 2010, 12(5):1081-1091.
[22] BRAUN M, HARTMANN P, JANA C. ¹⁹F and ³¹P NMR spectroscopy of calcium apatites[J]. J Mater Sci Mater Med, 1995, 6(3):150-154.
[23] KOLMAS J, KURAS M, OLEDZKA E, et al. A solid-state NMR study of selenium substitution into nanocrystalline hydroxyapatite[J]. Int J Mol Sci, 2015, 16(5):11452-11464.
[24] KOLMAS J, JAKLEWICZ A, ZIMA A, et al. Incorporation of carbonate and magnesium ions into synthetic hydroxyapatite:The effect on physicochemical properties[J]. J Mol Struct, 2011, 987(1-3):40-50.
[25] MARCHAT D, ZYMELKA M, COELHO C, et al. Accurate characterization of pure silicon-substituted hydroxyapatite powders synthesized by a new precipitation route[J]. Acta Biomater, 2013, 9(6):6992-7004.
[26] GRÖGER C, LUTZ K, BRUNNER E. NMR studies of biomineralisation[J]. Prog Nucl Magn Reson Spectrosc, 2009, 54(1):54-68.
[27] KOLODZIEJSKI W. New Techniques in solid-state NMR[M]. Berlin:Springer, 2005.
[28] GOOBES G, STAYTON P S, DROBNY G P. Solid state NMR studies of molecular recognition at protein-mineral interfaces[J]. Prog Nucl Magn Reson Spectrosc, 2007, 50(2, 3):71-85.
[29] BRADLEY J V, BRIDGLAND L N, COLYER D E, et al. NMR of biopolymer-apatite composites:Developing a model of the molecular structure of the mineral-matrix interface in calcium phosphate biomaterials[J]. Chem Mater, 2010, 22(22):6109-6116.
[30] BARHEINE S, HAYAKAWA S, OSAKA A, et al. Surface, interface, and bulk structure of borate containing apatitic biomaterials[J]. Chem Mater, 2009, 21(14):3102-3109.
[31] Cheng R H, Wu Z, Huang P C, et al. Sensitivity enhancement of multiple quantum and satellite transition magic angle spinning spectra by optimizing the initial state[J]. Chinese J Magn Reson, 2015, 32(2):363-372. 郑人豪, 吴振, 黄柏琦, 等. 优化初始脉冲增强多量子跃迁及卫星跃迁魔角旋转谱灵敏度[J]. 波谱学杂志, 2015, 32(2):363-372.
[32] Wang F F, Chen T H, Sun P C. Heterogeneous structure and miscibility of phenylboronic acid-rich chitosan nanoparticles as revealed by advanced solid-state NMR[J]. Chinese J Magn Reson, 2015, 32(2):354-362. 王粉粉, 陈铁红, 孙平川. 先进固体核磁共振揭示苯硼酸-壳聚糖纳米粒子非均匀结构和相容性[J]. 波谱学杂志, 2015, 32(2):354-362.
[33] LEGEROS R Z, LIN S, ROHANIZADEH R, et al. Biphasic calcium phosphate bioceramics:Preparation, properties and applications[J]. J Mater Sci Mater Med, 2003, 14(3):201-209.
[34] GAUTHIER O, BOULER J M, AGUADO E, et al. Macroporous biphasic calcium phosphate ceramics:Influence of macropore diameter and macroporosity percentage on bone ingrowth[J]. Biomaterials, 1998, 19(1-3):133-139.
[35] KLEIN C, DEGROOT K, DRIESSEN A A, et al. Interaction of biodegradable beta-whitlockite ceramics with bone tissue:An in vivo study[J]. Biomaterials, 1985, 6(3):189-192.
[36] GINTY F, FLYNN A, CASHMAN K D. The effect of dietary sodium intake on biochemical markers of bone metabolism in young women[J]. Brit J Nutr, 1998, 79(4):343-350.
[37] ITOH R, SUYAMA Y. Sodium excretion in relation to calcium and hydroxyproline excretion in a healthy Japanese population[J]. Am J Clin Nutr, 1996, 63(5):735-740.
[38] RUDE R K, GRUBER H E. Magnesium deficiency and osteoporosis:Animal and human observations[J]. J Nutr Biochem, 2004, 15(12):710-716.
[39] FEATHERSTONE J D B. Prevention and reversal of dental caries:Role of low level fluoride[J]. Community Dent Oral, 1999, 27(1):31-40.
[40] AIZENBERG J, BLACK A J, WHITESIDES G M. Control of crystal nucleation by patterned self-assembled monolayers[J]. Nature, 1999, 398(6727):495-498.
[41] WEINER S, ADDADI L. Design strategies in mineralized biological materials[J]. J Mater Chem, 1997, 7(5):689-702.
[42] STUPP S I, BRAUN P V. Molecular manipulation of microstructures:Biomaterials, ceramics, and semiconductors[J]. Science, 1997, 277(5330):1242-1248.
[43] CAO M, WANG Y, GUO C, et al. Preparation of ultrahigh-aspect-ratio hydroxyapatite nanofibers in reverse micelles under hydrothermal conditions[J]. Langmuir, 2004, 20(11):4784-4786.
[44] DONNERS J, NOLTE R J, SOMMERDIJK N. Dendrimer-based hydroxyapatite composites with remarkable materials properties[J]. Adv Mater, 2003, 15(4):313-316.
[45] SARDA S, HEUGHEBAERT M, LEBUGLE A. Influence of the type of surfactant on the formation of calcium phosphate in organized molecular systems[J]. Chem Mater, 1999, 11(10):2722-2727.
[46] HOANG Q Q, SICHERI F, HOWARD A J, et al. Bone recognition mechanism of porcine osteocalcin from crystal structure[J]. Nature, 2003, 425(6961):977-980.
[47] REES S G, SHELLIS R P, EMBERY G. Inhibition of hydroxyapatite crystal growth by bone proteoglycans and proteoglycan components[J]. Biochem Bioph Res Co, 2002, 292(3):727-733.
[48] BREKKEN R A, SAGE E H. SPARC, a matricellular protein:At the crossroads of cell-matrix communication[J]. Matrix Biol, 2001, 19(8):816-827.
[49] KNOTT L, BAILEY A J. Collagen cross-links in mineralizing tissues:A review of their chemistry, function, and clinical relevance[J]. Bone, 1998, 22(3):181-187.
[50] PROCKOP D J, KIVIRIKKO K I. Collagens:Molecular biology, diseases, and potentials for therapy[J]. Annu Rev Biochem, 1995, 64:403-434.
[51] LANDI E, TAMPIERI A, MATTIOLI-BELMONTE M, et al. Biomimetic Mg- and Mg, CO₃-substituted hydroxyapatites:Synthesis characterization and in vitro behaviour[J]. J Eur Ceram Soc, 2006, 26(13):2593-2601.
[52] HEANEY R P. Role of dietary sodium in osteoporosis[J]. J Am Coll Nutr, 2006, 25(S3):271-276.
[53] WISE E R, MALTSEV S, DAVIES M E, et al. The organic-mineral interface in bone is predominantly polysaccharide[J]. Chem Mater, 2007, 19(21):5055-5057.
[54] HE G, DAHL T, VEIS A, et al. Nucleation of apatite crystals in vitro by self-assembled dentin matrix protein 1[J]. Nat Mater, 2003, 2(8):552-558.
[55] LANDIS W J, SONG M J, LEITH A, et al. Mineral and organic matrix interaction in normally calcifying tendon visualized in three dimensions by high-voltage electron microscopic tomography and graphic image reconstruction[J]. J Struct Biol, 1993, 110(1):39-54.
[56] WEINER S, WAGNER H D. The material bone:Structure-mechanical function relations[J]. Annu Rev Mater Sci, 1998, 28:271-298.
[57] WEINER S, TRAUB W. Bone structure:From angstroms to microns[J]. Faseb J, 1992, 6(3):879-885.
[58] JAEGER C, GROOM N S, BOWE E A, et al. Investigation of the nature of the protein-mineral interface in bone by solid-state NMR[J]. Chem Mater, 2005, 17(12):3059-3061.
[59] BUEHLER J, CHAPPUIS P, SAFFAR J, et al. Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis)[J]. Bone, 2001, 29(2):176-179.
[60] GRYNPAS M, HAMILTON E, CHEUNG R, et al. Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect[J]. Bone, 1996, 18(3):253-259.
[61] ZHANG W, SHEN Y, PAN H, et al. Effects of strontium in modified biomaterials[J]. Acta Biomater, 2011, 7(2):800-808.
[62] ISAAC J, NOHRA J, LAO J, et al. Effects of strontium-doped bioactive glass on the differentiation of cultured osteogenic cells[J]. Eur Cell Mater, 2011, 21:130-143.
[63] RAFFALT A C, ANDERSEN J E, CHRISTGAU S. Application of inductively coupled plasma-mass spectrometry (ICP-MS) and quality assurance to study the incorporation of strontium into bone, bone marrow, and teeth of dogs after one month of treatment with strontium malonate[J]. Anal Bioanal Chem, 2008, 391(6):2199-2207.