Cited by 52Bone Tissue Engineering MaterialsTissue Engineering and Regenerative MedicineMedicinal Plant Pharmacodynamics Research

Effect of age on biomaterial-mediated in situ bone tissue regeneration

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Liu, Mengqian, Nakasaki, Manando, Shih, Yu-Ru Vernon, Varghese, Shyni·2018·Acta Biomaterialia

Abstract

Emerging studies show the potential application of synthetic biomaterials that are intrinsically osteoconductive and osteoinductive as bone grafts to treat critical bone defects. Here, the biomaterial not only assists recruitment of endogenous cells, but also supports cellular activities relevant to bone tissue formation and function. While such biomaterial-mediated in situ tissue engineering is highly attractive, success of such an approach relies largely on the regenerative potential of the recruited cells, which is anticipated to vary with age. In this study, we investigated the effect of the age of the host on mineralized biomaterial-mediated bone tissue repair using critical-sized cranial defects as a model system. Mice of varying ages, 1-month-old (juvenile), 2-month-old (young-adult), 6-month-old (middle-aged), and 14-month-old (elderly), were used as recipients. Our results show that the bio-mineralized scaffolds support bone tissue formation by recruiting endogenous cells for all groups albeit with differences in an age-related manner. Analyses of bone tissue formation after 2 and 8 weeks post-treatment show low mineral deposition and reduced number of osteocalcin and tartrate-resistant acid phosphatase (TRAP)-expressing cells in elderly mice. Statement of significance Tissue engineering strategies that promote tissue repair through recruitment of endogenous cells will have a significant impact in regenerative medicine. Previous studies from our group have shown that biomineralized materials containing calcium phosphate minerals can contribute to neo-bone tissue through recruitment and activation of endogenous cells. In this study, we investigated the effect of age of the recipient on biomaterial-mediated bone tissue repair. Our results show that the age of the recipient mouse had a significant impact on the quality and quantity of the engineered neo-bone tissues, in which delayed/compromised bone tissue formation was observed in older mice. These findings are in agreement with the clinical observations that age of patients is a key factor in bone repair.

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  • For this reason, sex, age, and comorbidities are also taken into consideration, thus allowing personalized TE.

    “For this reason, sex, age, and comorbidities are also taken into consideration, thus allowing personalized TE [202].”

    From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [202]

    The Introduction identifies recipient age as a host-specific factor in biomaterial-mediated bone repair, and the Conclusion reports that age significantly affected bone formation in mice. The paper does not establish that sex or comorbidities are taken into consideration, or that considering these factors enables personalized tissue engineering. (LLM, conf=0.87)

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  • The activity of the immune system, together with the body's regenerative capacity, greatly differs within individuals.

    “Additionally, immunoengineering also distinguishes that the activity of the immune system, together with the body’s regenerative capacity, greatly differs within individuals.”

    From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [202]

    The Discussion reports that bone regeneration differed substantially between mice of different ages and suggests that age-related changes in inflammatory environments could influence bone formation. It does not establish that immune-system activity itself differs greatly among individuals; its findings concern age-related bone repair in mice. (LLM, conf=0.84)

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  1. [1]Dimitriou R, Jones E, McGonagle D, Giannoudis PV, Bone regeneration: current concepts and future directions, BMC Med 9 (2011) 66. 21627784 PMC3123714
  2. [3]Lichte P, Pape HC, Pufe T, Kobbe P, Fischer H, Scaffolds for bone healing: Concepts, materials and evidence, Injury 42(6) (2011) 569– 573. 21489531
  3. [4]Laurie SWS, Kaban LB, Mulliken JB, Murray JE, Donor-Site Morbidity after Harvesting Rib and Iliac Bone, Plast Reconstr Surg 73(6) (1984) 933– 938. 6374708
  4. [5]Zlotolow DA, Vaccaro AR, Salamon ML, Albert TJ, The role of human bone morphogenetic proteins in spinal fusion, J Am Acad Orthop Surg 8(1) (2000) 3– 9. 10666648
  5. [6]Khan SN, Fraser JF, Sandhu HS, Cammisa FP, Girardi FP, Lane JM, Use of osteopromotive growth factors, demineralized bone matrix, and ceramics to enhance spinal fusion, J Am Acad Orthop Sur 13(2) (2005) 129– 137. 15850370
  6. [7]Campana V, Milano G, Pagano E, Barba M, Cicione C, Salonna G, Lattanzi W, Logroscino G, Bone substitutes in orthopaedic surgery: from basic science to clinical practice, J Mater Sci Mater Med 25(10) (2014) 2445– 61. 24865980 PMC4169585
  7. [8]Carragee EJ, Chu G, Rohatgi R, Hurwitz EL, Weiner BK, Yoon ST, Comer G, Kopjar B, Cancer Risk After Use of Recombinant Bone Morphogenetic Protein-2 for Spinal Arthrodesis, J Bone Joint Surg Am 95a(17) (2013) 1537– 1545. 24005193
  8. [9]Lad SP, Bagley JH, Karikari IO, Babu R, Ugiliweneza B, Kong MY, Isaacs RE, Bagley CA, Gottfried ON, Patil CG, Boakye M, Cancer After Spinal Fusion: The Role of Bone Morphogenetic Protein, Neurosurgery 73(3) (2013) 440– 449. 23756740
  9. [10]James AW, LaChaud G, Shen J, Asatrian G, Nguyen V, Zhang X, Ting K, Soo C, A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2, Tissue Eng Part B Rev 22(4) (2016) 284– 97. 26857241 PMC4964756
  10. [11]Yuan H, Yang Z, Li Y, Zhang X, De Bruijn JD, De Groot K, Osteoinduction by calcium phosphate biomaterials, J Mater Sci Mater Med 9(12) (1998) 723– 6. 15348929
  11. [12]Mygind T, Stiehler M, Baatrup A, Li H, Zou X, Flyvbjerg A, Kassem M, Bunger C, Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds, Biomaterials 28(6) (2007) 1036– 47. 17081601
  12. [13]Müller P, Bulnheim U, Diener A, Lüthen F, Teller M, Klinkenberg E-D, Neumann H-G, Nebe B, Liebold A, Steinhoff G, Rychly J, Calcium phosphate surfaces promote osteogenic differentiation of mesenchymal stem cells, J. Cell. Mol. Med. 12(1) (2008) 281– 291. 18366455 PMC3823489
  13. [14]Choi S-W, Zhang Y, Thomopoulos S, Xia Y, In Vitro Mineralization by Preosteoblasts in Poly(D, L-lactide-co-glycolide) Inverse Opal Scaffolds Reinforced with Hydroxyapatite Nanoparticles, Langmuir: the ACS journal of surfaces and colloids 26(14) (2010) 12126– 12131. 20450216 PMC2912416
  14. [15]Oyane A, Kim HM, Furuya T, Kokubo T, Miyazaki T, Nakamura T, Preparation and assessment of revised simulated body fluids, J Biomed Mater Res A 65(2) (2003) 188– 95. 12734811
  15. [16]Ducheyne P, Qiu Q, Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function, Biomaterials 20(23–24) (1999) 2287– 303. 10614935
  16. [17]Roberts SJ, Geris L, Kerckhofs G, Desmet E, Schrooten J, Luyten FP, The combined bone forming capacity of human periosteal derived cells and calcium phosphates, Biomaterials 32(19) (2011) 4393– 405. 21421268
  17. [18]Yuan H, Fernandes H, Habibovic P, de Boer J, Barradas AMC, de Ruiter A, Walsh WR, van Blitterswijk CA, de Bruijn JD, Osteoinductive ceramics as a synthetic alternative to autologous bone grafting, Proc. Natl. Acad. Sci. U. S. A. 107(31) (2010) 13614– 13619. 20643969 PMC2922269
  18. [19]Johal HS, Buckley RE, Le IL, Leighton RK, A prospective randomized controlled trial of a bioresorbable calcium phosphate paste (alpha-BSM) in treatment of displaced intra-articular calcaneal fractures, J Trauma 67(4) (2009) 875– 82. 19820600
  19. [20]Moore WR, Graves SE, Bain GI, Synthetic bone graft substitutes, ANZ J Surg 71(6) (2001) 354– 61. 11409021
  20. [21]Saiz E, Goldman M, Gomez-Vega JM, Tomsia AP, Marshall GW, Marshall SJ, In vitro behavior of silicate glass coatings on Ti6A14V, Biomaterials 23(17) (2002) 3749– 56. 12109700
  21. [22]Valerio P, Pereira MM, Goes AM, Leite MF, The effect of ionic products from bioactive glass dissolution on osteoblast proliferation and collagen production, Biomaterials 25(15) (2004) 2941– 8. 14967526
  22. [23]Shkilnyy A, Friedrich A, Tiersch B, Schone S, Fechner M, Koetz J, Schlapfer CW, Taubert A, Poly(ethylene imine)-controlled calcium phosphate mineralization, Langmuir 24(5) (2008) 2102– 9. 18205416
  23. [24]Song J, Saiz E, Bertozzi CR, A new approach to mineralization of biocompatible hydrogel scaffolds: an efficient process toward 3-dimensional bonelike composites, J Am Chem Soc 125(5) (2003) 1236– 43. 12553825
  24. [25]Kretlow JD, Mikos AG, Review: mineralization of synthetic polymer scaffolds for bone tissue engineering, Tissue Eng. 13(5) (2007) 927– 938. 17430090
  25. [26]Osathanon T, Linnes ML, Rajachar RM, Ratner BD, Somerman MJ, Giachelli CM, Microporous nanofibrous fibrin-based scaffolds for bone tissue engineering, Biomaterials 29(30) (2008) 4091– 9. 18640716 PMC2610368
  26. [27]Kang H, Shih Y-RV, Hwang Y, Wen C, Rao V, Seo T, Varghese S, Mineralized gelatin methacrylate-based matrices induce osteogenic differentiation of human induced pluripotent stem cells, Acta Biomater. 10(12) (2014) 4961– 4970. 25153779 PMC4252258
  27. [28]Kang H, Wen C, Hwang Y, Shih Y-RV, Kar M, Seo SW, Varghese S, Biomineralized matrix-assisted osteogenic differentiation of human embryonic stem cells, J. Mater. Chem. B Mater. Biol. Med 2(34) (2014) 5676– 5688. 25114796 PMC4126264
  28. [29]Wen C, Kang H, Shih Y-RV, Hwang Y, Varghese S, In vivo comparison of biomineralized scaffold-directed osteogenic differentiation of human embryonic and mesenchymal stem cells, Drug Deliv. Transl. Res 6(2) (2016) 121– 131. 26105532
  29. [30]Phadke A, Hwang Y, Kim SH, Kim SH, Yamaguchi T, Masuda K, Varghese S, Effect of scaffold microarchitecture on osteogenic differentiation of human mesenchymal stem cells, Eur Cell Mater 25 (2013) 114– 129. 23329467 PMC4387005
  30. [31]Shih Y-R, Phadke A, Yamaguchi T, Kang H, Inoue N, Masuda K, Varghese S, Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment, Acta Biomater 19 (2015) 1– 9. 25805106 PMC5644488
  31. [32]Gonzalez Diaz E, Shih Y, Nakasaki M, Liu M, Varghese S, Mineralized biomaterials mediated repair of bone defects through endogenous cells, Tissue Eng Part A (2018). PMC6033304 29368582
  32. [33]Nieminen S, Nurmi M, Satokari K, Healing of femoral neck fractures; influence of fracture reduction and age, Ann Chir Gynaecol 70(1) (1981) 26– 31. 7259056
  33. [34]Lu C, Hansen E, Sapozhnikova A, Hu D, Miclau T, Marcucio RS, Effect of age on vascularization during fracture repair, J Orthop Res 26(10) (2008) 1384– 9. 18464248 PMC2846969
  34. [35]Desai BJ, Meyer MH, Porter S, Kellam JF, Meyer RA Jr., The effect of age on gene expression in adult and juvenile rats following femoral fracture, J Orthop Trauma 17(10) (2003) 689– 98. 14600568
  35. [36]Skak SV, Jensen TT, Femoral shaft fracture in 265 children. Log-normal correlation with age of speed of healing, Acta Orthop Scand 59(6) (1988) 704– 7. 3213461
  36. [37]Zhou S, Greenberger JS, Epperly MW, Goff JP, Adler C, Leboff MS, Glowacki J, Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts, Aging Cell 7(3) (2008) 335– 43. 18248663 PMC2398731
  37. [38]D’Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA, Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow, J Bone Miner Res 14(7) (1999) 1115– 22. 10404011
  38. [39]O’Driscoll SW, Saris DB, Ito Y, Fitzimmons JS, The chondrogenic potential of periosteum decreases with age, J Orthop Res 19(1) (2001) 95– 103. 11332626
  39. [40]Fan W, Crawford R Fau - Xiao Y, Xiao Y, Structural and cellular differences between metaphyseal and diaphyseal periosteum in different aged rats, (8756– 3282 (Print)). 17962095
  40. [41]Meyer RA Jr., Desai BR, Heiner DE, Fiechtl J, Porter S, Meyer MH, Young, adult, and old rats have similar changes in mRNA expression of many skeletal genes after fracture despite delayed healing with age, J Orthop Res 24(10) (2006) 1933– 44. 16894589
  41. [43]Ayala R, Zhang C, Yang D, Hwang Y, Aung A, Shroff SS, Arce FT, Lal R, Arya G, Varghese S, Engineering the cell-material interface for controlling stem cell adhesion, migration, and differentiation, Biomaterials 32(15) (2011) 3700– 11. 21396708
  42. [44]Phadke A, Zhang C, Hwang Y, Vecchio K, Varghese S, Templated mineralization of synthetic hydrogels for bone-like composite materials: role of matrix hydrophobicity, Biomacromolecules 11(8) (2010) 2060– 8. 20690714
  43. [45]Phadke A, Shih Y-RV, Varghese S, Mineralized synthetic matrices as an instructive microenvironment for osteogenic differentiation of human mesenchymal stem cells, Macromol. Biosci 12(8) (2012) 1022– 1032. 22760917
  44. [46]Heinonen JK, Lahti RJ, A new and convenient colorimetric determination of inorganic orthophosphate and its application to the assay of inorganic pyrophosphatase, Anal Biochem 113(2) (1981) 313– 7. 6116463
  45. [47]Kang H, Shih YR, Nakasaki M, Kabra H, Varghese S, Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts, Sci Adv 2(8) (2016) e1600691. 27602403 PMC5007071
  46. [48]Shih YR, Kang H, Rao V, Chiu YJ, Kwon SK, Varghese S, In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism, Proc Natl Acad Sci U S A 114(21) (2017) 5419– 5424. 28484009 PMC5448182
  47. [49]Montjovent MO, Mathieu L, Schmoekel H, Mark S, Bourban PE, Zambelli PY, Laurent-Applegate LA, Pioletti DP, Repair of critical size defects in the rat cranium using ceramic-reinforced PLA scaffolds obtained by supercritical gas foaming, J Biomed Mater Res A 83a(1) (2007) 41– 51. 17377968
  48. [50]Chiu YC, Cheng MH, Engel H, Kao SW, Larson JC, Gupta S, Brey EM, The role of pore size on vascularization and tissue remodeling in PEG hydrogels, Biomaterials 32(26) (2011) 6045– 51. 21663958
  49. [51]Chen Y, Wang J, Zhu XD, Tang ZR, Yang X, Tan YF, Fan YJ, Zhang XD, Enhanced effect of beta-tricalcium phosphate phase on neovascularization of porous calcium phosphate ceramics: in vitro and in vivo evidence, Acta Biomater 11 (2015) 435– 48. 25246313
  50. [52]Furumatsu T, Shen ZN, Kawai A, Nishida K, Manabe H, Oohashi T, Inoue H, Ninomiya Y, Vascular endothelial growth factor principally acts as the main angiogenic factor in the early stage of human osteoblastogenesis, J Biochem 133(5) (2003) 633– 639. 12801915
  51. [53]Steinbrech DS, Mehrara BJ, Saadeh PB, Chin G, Dudziak ME, Gerrets RP, Gittes GK, Longaker MT, Hypoxia regulates VEGF expression and cellular proliferation by osteoblasts in vitro, Plast Reconstr Surg 104(3) (1999) 738– 747. 10456527
  52. [54]Huang W, Yang S, Shao J, Li YP, Signaling and transcriptional regulation in osteoblast commitment and differentiation, Front Biosci 12 (2007) 3068– 92. 17485283 PMC3571113
  53. [55]Wozney JM, The potential role of bone morphogenetic proteins in periodontal reconstruction, J Periodontol 66(6) (1995) 506– 10. 7562340
  54. [56]Bolander ME, Regulation of fracture repair by growth factors, Proc Soc Exp Biol Med 200(2) (1992) 165– 70. 1374563
  55. [57]Deckers MM, van Bezooijen RL, van der Horst G, Hoogendam J, van Der Bent C, Papapoulos SE, Lowik CW, Bone morphogenetic proteins stimulate angiogenesis through osteoblast-derived vascular endothelial growth factor A, Endocrinology 143(4) (2002) 1545– 53. 11897714
  56. [58]Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N, VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation, Nat Med 5(6) (1999) 623– 8. 10371499
  57. [59]Matsuo K, Irie N, Osteoclast-osteoblast communication, Archives of biochemistry and biophysics 473(2) (2008) 201– 209. 18406338
  58. [61]Teti A, Mechanisms of osteoclast-dependent bone formation, Bonekey Rep 2 (2013) 449. 24422142 PMC3872977
  59. [62]Teitelbaum SL, Bone resorption by osteoclasts, Science 289(5484) (2000) 1504– 8. 10968780
  60. [63]Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C, Asano M, Iwakura Y, Suda T, Matsuo K, Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis, J Biol Chem 284(21) (2009) 14637– 44. 19299512 PMC2682911
  61. [65]Mundy GR, Local control of bone formation by osteoblasts, Clin Orthop Relat Res (313) (1995) 19– 26. 7641479
  62. [66]Hayda RA, Brighton CT, Esterhai JL Jr., Pathophysiology of delayed healing, Clin Orthop Relat Res (355 Suppl) (1998) S31– 40. 9917624
  63. [67]Cummings SR, Melton LJ, Epidemiology and outcomes of osteoporotic fractures, Lancet 359(9319) (2002) 1761– 7. 12049882
  64. [68]Gruber R, Koch H, Doll BA, Tegtmeier F, Einhorn TA, Hollinger JO, Fracture healing in the elderly patient, Exp Gerontol 41(11) (2006) 1080– 93. 17092679
  65. [69]Lu C, Miclau T, Hu D, Hansen E, Tsui K, Puttlitz C, Marcucio RS, Cellular basis for age-related changes in fracture repair, J Orthop Res 23(6) (2005) 1300– 7. 15936915 PMC2844440
  66. [70]Sethe S, Scutt A, Stolzing A, Aging of mesenchymal stem cells, Ageing Res Rev 5(1) (2006) 91– 116. 16310414
  67. [71]Beane OS, Fonseca VC, Cooper LL, Koren G, Darling EM, Impact of aging on the regenerative properties of bone marrow-, muscle-, and adipose-derived mesenchymal stem/stromal cells, PLoS One 9(12) (2014) e115963. 25541697 PMC4277426
  68. [72]Asumda FZ, Chase PB, Age-related changes in rat bone-marrow mesenchymal stem cell plasticity, BMC Cell Biol 12 (2011) 44. 21992089 PMC3204286
  69. [73]Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ, Bellantuono I, Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion, Stem Cells 22(5) (2004) 675– 82. 15342932
  70. [74]Nishida S, Endo N, Yamagiwa H, Tanizawa T, Takahashi HE, Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation, J Bone Miner Metab 17(3) (1999) 171– 7. 10757676
  71. [75]Stenderup K, Justesen J, Clausen C, Kassem M, Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells, Bone 33(6) (2003) 919– 26. 14678851
  72. [76]Duscher D, Rennert RC, Januszyk M, Anghel E, Maan ZN, Whittam AJ, Perez MG, Kosaraju R, Hu MS, Walmsley GG, Atashroo D, Khong S, Butte AJ, Gurtner GC, Aging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells, Sci Rep 4 (2014) 7144. 25413454 PMC4239576
  73. [77]Rosen CJ, Donahue LR, Hunter SJ, Insulin-like growth factors and bone: the osteoporosis connection, Proc Soc Exp Biol Med 206(2) (1994) 83– 102. 8208742
  74. [78]Boonen S, Mohan S, Dequeker J, Aerssens J, Vanderschueren D, Verbeke G, Broos P, Bouillon R, Baylink DJ, Down-regulation of the serum stimulatory components of the insulin-like growth factor (IGF) system (IGF-I, IGF-II, IGF binding protein [BP]-3, and IGFBP-5) in age-related (type II) femoral neck osteoporosis, J Bone Miner Res 14(12) (1999) 2150– 8. 10620075
  75. [79]Rivard A, Fabre JE, Silver M, Chen D, Murohara T, Kearney M, Magner M, Asahara T, Isner JM, Age-dependent impairment of angiogenesis, Circulation 99(1) (1999) 111– 20. 9884387
  76. [80]Ramasamy SK, Kusumbe AP, Schiller M, Zeuschner D, Bixel MG, Milia C, Gamrekelashvili J, Limbourg A, Medvinsky A, Santoro MM, Limbourg FP, Adams RH, Blood flow controls bone vascular function and osteogenesis, Nat Commun 7 (2016) 13601. 27922003 PMC5150650
  77. [81]Dutta S, Sengupta P, Men and mice: Relating their ages, Life Sci 152 (2016) 244– 8. 26596563
  78. [82]Choudhery MS, Khan M, Mahmood R, Mehmood A, Khan SN, Riazuddin S, Bone marrow derived mesenchymal stem cells from aged mice have reduced wound healing, angiogenesis, proliferation and anti-apoptosis capabilities, Cell Biol Int 36(8) (2012) 747– 53. 22352320
  79. [83]Bruunsgaard H, Pedersen BK, Age-related inflammatory cytokines and disease, Immunol Allergy Clin North Am 23(1) (2003) 15– 39. 12645876
  80. [84]Gerstenfeld LC, Cho TJ, Kon T, Aizawa T, Cruceta J, Graves BD, Einhorn TA, Impaired intramembranous bone formation during bone repair in the absence of tumor necrosis factor-alpha signaling, Cells Tissues Organs 169(3) (2001) 285– 94. 11455125
  81. [85]Ito H, Chemokines in mesenchymal stem cell therapy for bone repair: a novel concept of recruiting mesenchymal stem cells and the possible cell sources, Mod Rheumatol 21 (2) (2011) 113– 21. 20830500
  82. [86]Spicer PP, Kretlow JD, Young S, Jansen JA, Kasper FK, Mikos AG, Evaluation of bone regeneration using the rat critical size calvarial defect, Nat Protoc 7(10) (2012) 1918– 29. 23018195 PMC3513397

Cited by

Sorted by citations

Authors
Liu, M., Nakasaki, M., Shih, Y.-R. V., & Varghese, S.
Affiliations
  • Duke University (US)
  • University of California San Diego (US)
Corresponding author
Varghese, Shyni
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2018-09
Volume
78
Pages
329-340
ISSN
1742-7061 (ISSN-L)
OpenAlex
W2810718827
Cited by
52
References
3
Citations by year
2026: 6 · 2025: 4 · 2024: 13 · 2023: 6 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 4
FWCI
1.95
Type
journal article
Language
en
Open access
Locations
  • Acta Biomaterialia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR071552, R01AR063184)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Medicinal Plant Pharmacodynamics Research
Keywords
calcium phosphate, osteocalcin, TRAP-positive osteoclasts, bone grafting, osteoconduction, osteoinduction
MeSH terms
Aging, Animals, Biocompatible Materials, Bone and Bones, Bone Regeneration, Female, Mice, Inbred C57BL, Osteogenesis, Skull, Biomarkers, Neovascularization, Physiologic

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