CoChat
Sign Up
Cited by 556Bone Tissue Engineering MaterialsHydrogels: synthesis, properties, applicationsWound Healing and Treatments

Bioactive hydrogels for bone regeneration

Open access
Bai, Xin, Gao, Mingzhu, Syed, Sahla, Zhuang, Jerry, Xu, Xiaoyang, Zhang, Xue-Qing·2018·Bioactive Materials
DOI 10.1016/j.bioactmat.2018.05.006PMC PMC6038268
Open this paper in CoChat — free accountOpen PDF

Abstract

Bone self-healing is limited and generally requires external intervention to augment bone repair and regeneration. While traditional methods for repairing bone defects such as autografts, allografts, and xenografts have been widely used, they all have corresponding disadvantages, thus limiting their clinical use. Despite the development of a variety of biomaterials, including metal implants, calcium phosphate cements (CPC), hydroxyapatite, etc., the desired therapeutic effect is not fully achieved. Currently, polymeric scaffolds, particularly hydrogels, are of interest and their unique configurations and tunable physicochemical properties have been extensively studied. This review will focus on the applications of various cutting-edge bioactive hydrogels systems in bone regeneration, as well as their advantages and limitations. We will examine the composition and defects of the bone, discuss the current biomaterials for bone regeneration, and classify recently developed polymeric materials for hydrogel synthesis. We will also elaborate on the properties of desirable hydrogels as well as the fabrication techniques and different delivery strategies. Finally, the existing challenges, considerations, and the future prospective of hydrogels in bone regeneration will be outlined.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.bioactmat.2018.05.006

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Hydrogels can offer robust mechanical support for cell adhesion and effectively encapsulate bioactive growth factors or cells.

    “Hydrogels, serving as versatile polymeric scaffolds, are capable of offering robust mechanical support for cell adhesion and can effectively encapsulate bioactive growth factors or cells [133].”

    From Mussel-Inspired Injectable Adhesive Hydrogels for Biomedical Applications (2024) · cites this paper as [133]

  • Integration of bioactive growth factors within scaffolds promotes bone repair and regeneration.

    “In bone tissue engineering, the integration of bioactive growth factors within scaffolds has emerged as an innovative approach to promote bone repair and regeneration [133].”

    From Mussel-Inspired Injectable Adhesive Hydrogels for Biomedical Applications (2024) · cites this paper as [133]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 106

  1. [1]Vo T.N. Kasper F.K. Mikos A.G. Strategies for controlled delivery of growth factors and cells for bone regeneration Adv. Drug Deliv. Rev. 64 2012 1292 1309 22342771 PMC3358582
  2. [2]Velasco M.A. Narvaez-Tovar C.A. Garzon-Alvarado D.A. Design, materials, and mechanobiology of biodegradable scaffolds for bone tissue engineering BioMed Res. Internat. 2015 2015 729076 PMC4391163 25883972
  3. [4]Agarwal R. García A.J. Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair Adv. Drug Deliv. Rev. 94 2015 53 62 25861724 PMC4598264
  4. [5]Forlino A. Marini J.C. Osteogenesis imperfecta Lancet 387 2016 1657 1671 26542481 PMC7384887
  5. [6]Smolen J.S. Aletaha D. McInnes I.B. Rheumatoid arthritis Lancet 388 2016 2023 2038 27156434
  6. [8]Street J. Bao M. deGuzman L. Bunting S. Peale F.V. Ferrara N. Jr. Steinmetz H. Hoeffel J. Cleland J.L. Daugherty A. van Bruggen N. Redmond H.P. Carano R.A. Filvaroff E.H. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover Proc. Natl. Acad. Sci. U. S. A. 99 2002 9656 9661 12118119 PMC124965
  7. [9]Lee K. Chan C.K. Patil N. Goodman S.B. Cell therapy for bone regeneration–bench to bedside J. Biomed. Mater. Res. B Appl. Biomater. 89 2009 252 263 18777578
  8. [11]Quinlan E. Lopez-Noriega A. Thompson E. Kelly H.M. Cryan S.A. O'Brien F.J. Development of collagen-hydroxyapatite scaffolds incorporating PLGA and alginate microparticles for the controlled delivery of rhBMP-2 for bone tissue engineering J. Contr. Release 198 2015 71 79 25481441
  9. [13]Wu G. Feng C. Quan J. Wang Z. Wei W. Zang S. Kang S. Hui G. Chen X. Wang Q. In situ controlled release of stromal cell-derived factor-1alpha and antimiR-138 for on-demand cranial bone regeneration Carbohydr. Polym. 182 2018 215 224 29279118
  10. [14]Silva R. Fabry B. Boccaccini A.R. Fibrous protein-based hydrogels for cell encapsulation Biomaterials 35 2014 6727 6738 24836951
  11. [15]Gong T. Xie J. Liao J. Zhang T. Lin S. Lin Y. Nanomaterials and bone regeneration Bone Res 3 2015 15029 26558141 PMC4639780
  12. [16]Bueno E.M. Glowacki J. Cell-free and cell-based approaches for bone regeneration Nat. Rev. Rheumatol. 5 2009 685 697 19901916
  13. [17]Carrington J.L. Aging bone and cartilage: cross-cutting issues Biochem. Biophys. Res. Commun. 328 2005 700 708 15694404
  14. [18]Baroli B. From natural bone grafts to tissue engineering therapeutics: brainstorming on pharmaceutical formulative requirements and challenges J. Pharmaceut. Sci. 98 2009 1317 1375 18729202
  15. [19]Lew D.P. Waldvogel F.A. Osteomyelitis N. Engl. J. Med. 336 1997 999 1007 9077380
  16. [20]Wijewardena A. Vandervord E. Lajevardi S.S. Vandervord J. Jackson C.J. Combination of activated protein C and topical negative pressure rapidly regenerates granulation tissue over exposed bone to heal recalcitrant orthopedic wounds Int. J. Low. Extrem. Wounds 10 2011 146 21807809
  17. [21]Jimenez-Andrade J.M. Mantyh W.G. Bloom A.P. Ferng A.S. Geffre C.P. Mantyh P.W. Bone cancer pain Ann. N. Y. Acad. Sci. 1198 2010 173 181 20536932 PMC5642911
  18. [22]Duncan G. McCormick C. Tufaro F. The link between heparan sulfate and hereditary bone disease: finding a function for the EXT family of putative tumor suppressor proteins J. Clin. Invest. 108 2001 511 516 11518722 PMC209410
  19. [23]Bizzetto R. Bonfim C. Rocha V. Socie G. Locatelli F. Chan K. Ramirez O. Stein J. Nabhan S. Miranda E. Passweg J. de Souza C.A. Gluckman E. Eurocord, S.-W.f. EBMT Outcomes after related and unrelated umbilical cord blood transplantation for hereditary bone marrow failure syndromes other than Fanconi anemia Haematologica 96 2011 134 141 21071499 PMC3012777
  20. [24]Saleh M.M. Touny A.H. Al-Omair M.A. Saleh M.M. Biodegradable/biocompatible coated metal implants for orthopedic applications Bio Med. Mater. Eng. 27 2016 87 99 27175470
  21. [25]Ducheyne P. Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function Biomaterials 20 1999 2287 2303 10614935
  22. [26]Nauth A. Lane J. Watson J.T. Giannoudis P. Bone graft substitution and augmentation J. Orthop. Trauma 29 2015 S34 S38 26584264
  23. [27]Fu T.S. Wang I.C. Lu M.L. Hsieh M.K. Chen L.H. Chen W.J. The fusion rate of demineralized bone matrix compared with autogenous iliac bone graft for long multi-segment posterolateral spinal fusion BMC Muscoskel. Disord. 17 2016 3 PMC4700670 26728876
  24. [28]Gupta A. Kukkar N. Sharif K. Main B.J. Albers C.E. El-Amin Iii S.F. Bone graft substitutes for spine fusion: a brief review World J. Orthoped. 6 2015 449 456 PMC4501930 26191491
  25. [29]Leupold J.A. Barfield W.R. An Y.H. Hartsock L.A. A comparison of ProOsteon, DBX, and collagraft in a rabbit model J. Biomed. Mater. Res. B Appl. Biomater. 79 2006 292 297 16649170
  26. [30]Bansiddhi A. Sargeant T.D. Stupp S.I. Dunand D.C. Porous NiTi for bone implants: a review Acta Biomater. 4 2008 773 782 18348912 PMC3068602
  27. [31]Oryan A. Alidadi S. Moshiri A. Maffulli N. Bone regenerative medicine: classic options, novel strategies, and future directions J. Orthop. Surg. Res. 9 2014 27 24628910 PMC3995444
  28. [32]Kattimani V. Lingamaneni K.P. Chakravarthi P.S. Kumar T.S. Siddharthan A. Eggshell-derived hydroxyapatite: a new era in bone regeneration J. Craniofac. Surg. 27 2016 112 117 26674907
  29. [33]van Vugt T.A. Geurts J. Arts J.J. Clinical application of antimicrobial bone graft substitute in osteomyelitis treatment: a systematic review of different bone graft substitutes available in clinical treatment of osteomyelitis BioMed Res. Int. 2016 2016 6984656 PMC4745864 26904683
  30. [34]van Houdt C.I. Tim C.R. Crovace M.C. Zanotto E.D. Peitl O. Ulrich D.J. Jansen J.A. Parizotto N.A. Renno A.C. van den Beucken J.J. Bone regeneration and gene expression in bone defects under healthy and osteoporotic bone conditions using two commercially available bone graft substitutes Biomed. Mater. 10 2015 035003 25953955
  31. [35]Basha R.Y. Doble M. Design of biocomposite materials for bone tissue regeneration Mater. Sci. Eng. C 57 2015 452 463 26354284
  32. [36]Laurencin C. Khan Y. El-Amin S.F. Bone graft substitutes Expet Rev. Med. Dev. 3 2006 49 57 16359252
  33. [37]Dahabreh Z. Panteli M. Pountos I. Howard M. Campbell P. Giannoudis P.V. Ability of bone graft substitutes to support the osteoprogenitor cells: an in-vitro study World J. Stem Cell. 6 2014 497 504 PMC4172679 25258672
  34. [38]Bojar W. Ciach T. Kucharska M. Maurin J. Gruber B.M. Krzyszton-Russjan J. Bubko I. Anuszewska E.L. Cytotoxicity Evaluation and Crystallochemical Analysis of a Novel and Commercially Available Bone Substitute Material Adv. Clin. Exp. Med. 24 2015 511 516 26467142
  35. [40]Lee S.H. Shin H. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering Adv. Drug Deliv. Rev. 59 2007 339 359 17499384
  36. [41]Ullah F. Othman M.B. Javed F. Ahmad Z. Md Akil H. Classification, processing and application of hydrogels: a review Mat. sci. eng. C, Mater. Sci. Eng. C, Mat. biol. appl. 57 2015 414 433 26354282
  37. [43]Lindsey W.H. Ogle R.C. Morgan R.F. Cantrell R.W. Sweeney T.M. Nasal reconstruction using an osteoconductive collagen gel matrix Arch. Otolaryngol. Head Neck Surg. 122 1996 37 40 8554744
  38. [44]Patterson J. Siew R. Herring S.W. Lin A.S.P. Guldberg R. Stayton P.S. Hyaluronic acid hydrogels with controlled degradation properties for oriented bone regeneration Biomaterials 31 2010 6772 6781 20573393 PMC2907529
  39. [46]Mredha M.T.I. Kitamura N. Nonoyama T. Wada S. Goto K. Zhang X. Nakajima T. Kurokawa T. Takagi Y. Yasuda K. Gong J.P. Anisotropic tough double network hydrogel from fish collagen and its spontaneous in vivo bonding to bone Biomaterials 132 2017 85 95 28411451
  40. [48]Sabir M.I. Xu X. Li L. A review on biodegradable polymeric materials for bone tissue engineering applications J. Mater. Sci. 44 2009 5713 5724
  41. [49]Dhandayuthapani B. Yoshida Y. Maekawa T. Kumar D.S. Polymeric scaffolds in tissue engineering application: a review International Journal of Polymer Science 2011 2011 1 19
  42. [50]Lee K.Y. Alsberg E. Mooney D.J. Degradable and injectable poly(aldehyde guluronate) hydrogels for bone tissue engineering J. Biomed. Mater. Res. 56 2001 228 233 11340593
  43. [51]Wang W. Deng L. Liu S. Li X. Zhao X. Hu R. Zhang J. Han H. Dong A. Adjustable degradation and drug release of a thermosensitive hydrogel based on a pendant cyclic ether modified poly(epsilon-caprolactone) and poly(ethylene glycol)co-polymer Acta Biomater. 8 2012 3963 3973 22835677
  44. [52]Dey R.E. Wimpenny I. Gough J.E. Watts D.C. Budd P.M. Poly (vinylphosphonic acid-co-acrylic acid) hydrogels: the effect of copolymer composition on osteoblast adhesion and proliferation J. Biomed. Mater. Res. 106 2018 255 264 PMC5725815 28891249
  45. [53]Dawson E. Mapili G. Erickson K. Taqvi S. Roy K. Biomaterials for stem cell differentiation Adv. Drug Deliv. Rev. 60 2008 215 228 17997187
  46. [54]Thoma D.S. Weber F.E. Bienz S.P. Ge Y. Hämmerle C.H. Jung R.E. Biodegradation and tissue integration of various polyethylene glycol matrices: a comparative study in rabbits Clin. Oral Implants Res. 28 11 2017 e244 e251 28111809
  47. [55]Sugaya S. Miyama A. Yamada M. Seki M. Fabrication of Functional Hydrogel Microbeads Utilizing Non-equilibrium Microfluidics for Biological Applications 2011 International Symposium on Micro-NanoMechatronics and Human Science, IEEE 2011 75 78
  48. [56]Sugaya S. Yamada M. Seki M. Manipulation of cells and cell spheroids using collagen hydrogel microbeads prepared by microfluidic devices 2012 International Symposium on Micro-NanoMechatronics and Human Science, IEEE 2012 435 438
  49. [57]Moshaverinia A. Chen C. Akiyama K. Xu X. Chee W.W.L. Schricker S.R. Shi S. Encapsulated dental-derived mesenchymal stem cells in an injectable and biodegradable scaffold for applications in bone tissue engineering J. Biomed. Mater. Res. 101 2013 3285 3294 23983201
  50. [58]Leslie S.K. Cohen D.J. Sedlaczek J. Pinsker E.J. Boyan B.D. Schwartz Z. Controlled release of rat adipose-derived stem cells from alginate microbeads Biomaterials 34 2013 8172 8184 23906513
  51. [59]Wang L. Rao R.R. Stegemann J.P. Delivery of mesenchymal stem cells in chitosan/collagen microbeads for orthopedic tissue repair Cells Tissues Organs 197 2013 333 343 23571151 PMC3711684
  52. [60]Wise J.K. Alford A.I. Goldstein S.A. Stegemann J.P. Synergistic enhancement of ectopic bone formation by supplementation of freshly isolated marrow cells with purified MSC in collagen-chitosan hydrogel microbeads Connect. Tissue Res. 57 2016 516 525 26337827 PMC4864208
  53. [61]Vinogradov S.V. Bronich T.K. Kabanov A.V. Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells Adv. Drug Deliv. Rev. 54 2002 135 147 11755709
  54. [62]Zhang H. Zhai Y.J. Wang J. Zhai G.X. New progress and prospects: the application of nanogel in drug delivery Mat. S. Eng. C-Mat. Biol. Appl. 60 2016 560 568 26706564
  55. [63]Themistocleous G.S. Katopodis H.A. Khaldi L. Papalois A. Doillon C. Sourla A. Soucacos P.N. Koutsilieris M. Implants of type I collagen gel containing MG-63 osteoblast-like cells can act as stable scaffolds stimulating the bone healing process at the sites of the surgically-produced segmental diaphyseal defects in male rabbits In Vivo 21 2007 69 76 17354616
  56. [64]Fujioka-Kobayashi M. Ota M.S. Shimoda A. Nakahama K.-i. Akiyoshi K. Miyamoto Y. Iseki S. Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering Biomaterials 33 2012 7613 7620 22800537
  57. [65]Miyahara T. Nyan M. Shimoda A. Yamamoto Y. Kuroda S. Shiota M. Akiyoshi K. Kasugai S. Exploitation of a novel polysaccharide nanogel cross-linking membrane for guided bone regeneration (GBR) Regen. Med. Tissue Eng. 6 2012 666 672 22095663
  58. [67]Young D.A. Pimentel M.B. Lima L.D. Custodio A.F. Lo W.C. Chen S.C. Teymour F. Papavasiliou G. Design and characterization of hydrogel nanoparticles with tunable network characteristics for sustained release of a VEGF-mimetic peptide Biomater. Sci. 5 2017 2079 2092 28744527
  59. [68]Seo B.B. Choi H. Koh J.T. Song S.C. Sustained BMP-2 delivery and injectable bone regeneration using thermosensitive polymeric nanoparticle hydrogel bearing dual interactions with BMP-2 J. Contr. Release 209 2015 67 76 25910579
  60. [69]Ignatova M. Manolova N. Markova N. Rashkov I. Electrospun non-woven nanofibrous hybrid mats based on chitosan and PLA for wound-dressing applications Macromol. Biosci. 9 2009 102 111 18855947
  61. [70]Guvendiren M. Burdick J.A. Engineering synthetic hydrogel microenvironments to instruct stem cells Curr. Opin. Biotechnol. 24 2013 841 846 23545441 PMC3783596
  62. [71]Sugaya S. Yamada M. Hori A. Seki M. Microfluidic production of single micrometer-sized hydrogel beads utilizing droplet dissolution in a polar solvent Biomicrofluidics 7 2013 054120 PMC3820636 24396529
  63. [72]Cheng J. Jun Y. Qin J. Lee S.H. Electrospinning versus microfluidic spinning of functional fibers for biomedical applications Biomaterials 114 2017 121 143 27880892
  64. [73]Tang M. Chen W. Weir M.D. Thein-Han W. Xu H.H.K. Human embryonic stem cell encapsulation in alginate microbeads in macroporous calcium phosphate cement for bone tissue engineering Acta Biomater. 8 2012 3436 3445 22633970 PMC3408764
  65. [74]Lin H.Y. Peng C.W. Wu W.W. Fibrous hydrogel scaffolds with cells embedded in the fibers as a potential tissue scaffold for skin repair J. Mater. Sci. Mater. Med. 25 2014 259 269 24101186
  66. [75]Hu M. Deng R. Schumacher K.M. Kurisawa M. Ye H. Purnamawati K. Ying J.Y. Hydrodynamic spinning of hydrogel fibers Biomaterials 31 2010 863 869 19878994
  67. [76]Heo Y.J. Shibata H. Okitsu T. Kawanishi T. Takeuchi S. Long-term in vivo glucose monitoring using fluorescent hydrogel fibers Proc. Natl. Acad. Sci. U. S. A. 108 2011 13399 13403 21808049 PMC3158145
  68. [78]Perez R.A. Kim J.H. Buitrago J.O. Wall I.B. Kim H.W. Novel therapeutic core-shell hydrogel scaffolds with sequential delivery of cobalt and bone morphogenetic protein-2 for synergistic bone regeneration Acta Biomater. 23 2015 295 308 26054564
  69. [79]Hu M. Kurisawa M. Deng R. Teo C.M. Schumacher A. Thong Y.X. Wang L. Schumacher K.M. Ying J.Y. Cell immobilization in gelatin-hydroxyphenylpropionic acid hydrogel fibers Biomaterials 30 2009 3523 3531 19328545
  70. [80]Im J.S. Yun J. Lim Y.M. Kim H.I. Lee Y.S. Fluorination of electrospun hydrogel fibers for a controlled release drug delivery system Acta Biomater. 6 2010 102 109 19531386
  71. [81]Wang L. Wang P. Weir M.D. Reynolds M.A. Zhao L. Xu H.H. Hydrogel fibers encapsulating human stem cells in an injectable calcium phosphate scaffold for bone tissue engineering Biomed. Mater. 11 2016 065008 PMC5382017 27811389
  72. [82]Lee K. Silva E.A. Mooney D.J. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments J. R. Soc. Interface 8 2011 153 170 20719768 PMC3033020
  73. [83]Tessmar J.K. Gopferich A.M. Matrices and scaffolds for protein delivery in tissue engineering Adv. Drug Deliv. Rev. 59 2007 274 291 17544542
  74. [84]Yun Y.R. Jang J.H. Jeon E. Kang W. Lee S. Won J.E. Kim H.W. Wall I. Administration of growth factors for bone regeneration Regen. Med. 7 2012 369 385 22594329
  75. [85]Bai Z. Guo X.H. Tang C. Yue S.T. Shi L. Qiang B. Effects of artesunate on the expressions of insulin-like growth Factor-1, osteopontin and C-Telopeptides of type II collagen in a rat model of osteoarthritis Pharmacology 101 2018 1 8 28898893
  76. [86]Street J. Bao M. Bunting S. Peale F.V. Ferrara N. Steinmetz H. Hoeffel J. Cleland J.L. Daugherty A. van Bruggen N. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover Proc. Natl. Acad. Sci. Unit. States Am. 99 2002 9656 9661 PMC124965 12118119
  77. [87]Mi L. Liu H. Gao Y. Miao H. Ruan J. Injectable nanoparticles/hydrogels composite as sustained release system with stromal cell-derived factor-1alpha for calvarial bone regeneration Int. J. Biol. Macromol. 101 2017 341 347 28330754
  78. [88]Fujioka-Kobayashi M. Ota M.S. Shimoda A. Nakahama K. Akiyoshi K. Miyamoto Y. Iseki S. Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering Biomaterials 33 2012 7613 7620 22800537
  79. [89]Zara J.N. Siu R.K. Zhang X. Shen J. Ngo R. Lee M. Li W. Chiang M. Chung J. Kwak J. Wu B.M. Ting K. Soo C. High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo Tissue Eng. 17 2011 1389 1399 PMC3079169 21247344
  80. [90]Moshaverinia A. Chen C. Akiyama K. Xu X. Chee W.W. Schricker S.R. Shi S. Encapsulated dental-derived mesenchymal stem cells in an injectable and biodegradable scaffold for applications in bone tissue engineering J. Biomed. Mater. Res. 101 2013 3285 3294 23983201
  81. [91]Shekaran A. Garcia J.R. Clark A.Y. Kavanaugh T.E. Lin A.S. Guldberg R.E. Garcia A.J. Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle Biomaterials 35 2014 5453 5461 24726536 PMC4033404
  82. [92]Shirakura T. Smith C. Hopkins T.J.J. Koo Lee Y.E. Lazaridis F. Argyrakis P. Kopelman R. Matrix density engineering of hydrogel nanoparticles with simulation-guided synthesis for tuning drug release and cellular uptake ACS Omega 2 2017 3380 3389 28782048 PMC5537717
  83. [93]Seo B.B. Koh J.T. Song S.C. Tuning physical properties and BMP-2 release rates of injectable hydrogel systems for an optimal bone regeneration effect Biomaterials 122 2017 91 104 28110173
  84. [94]Holloway J.L. Ma H. Rai R. Burdick J.A. Modulating hydrogel crosslink density and degradation to control bone morphogenetic protein delivery and in vivo bone formation J. Contr. Release 191 2014 63 70 PMC4156908 24905414
  85. [95]Tremolada C. Palmieri G. Ricordi C. Adipocyte transplantation and stem cells: plastic surgery meets regenerative medicine Cell Transplant. 19 2010 1217 1223 20444320
  86. [96]Li Z. Han Z. Wu J.C. Transplantation of human embryonic stem cell-derived endothelial cells for vascular diseases J. Cell. Biochem. 106 2009 194 199 19097085 PMC2866109
  87. [97]Gimble J.M. Katz A.J. Bunnell B.A. Adipose-derived stem cells for regenerative medicine Circ. Res. 100 2007 1249 1260 17495232 PMC5679280
  88. [98]Kern S. Eichler H. Stoeve J. Kluter H. Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue Stem Cell. 24 2006 1294 1301 16410387
  89. [99]Jones E. Yang X. Mesenchymal stem cells and bone regeneration: current status Injury 42 2011 562 568 21489533
  90. [100]Zhao L. Weir M.D. Xu H.H. An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering Biomaterials 31 2010 6502 6510 20570346 PMC3001248
  91. [101]Niemeyer P. Fechner K. Milz S. Richter W. Suedkamp N.P. Mehlhorn A.T. Pearce S. Kasten P. Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma Biomaterials 31 2010 3572 3579 20153047
  92. [102]Agung M. Ochi M. Yanada S. Adachi N. Izuta Y. Yamasaki T. Toda K. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration Knee Surg. Sports Traumatol. Arthrosc. 14 2006 1307 1314 16788809
  93. [103]Burdick J.A. Mauck R.L. Gerecht S. To serve and protect: hydrogels to improve stem cell-based therapies Cell Stem Cell 18 2016 13 15 26748751
  94. [105]Huebsch N. Lippens E. Lee K. Mehta M. Koshy S.T. Darnell M.C. Desai R.M. Madl C.M. Xu M. Zhao X. Chaudhuri O. Verbeke C. Kim W.S. Alim K. Mammoto A. Ingber D.E. Duda G.N. Mooney D.J. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation Nat. Mater. 14 2015 1269 1277 26366848 PMC4654683
  95. [107]Huebsch N. Arany P.R. Mao A.S. Shvartsman D. Ali O.A. Bencherif S.A. Rivera-Feliciano J. Mooney D.J. Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate Nat. Mater. 9 2010 518 526 20418863 PMC2919753
  96. [108]Chaudhuri O. Gu L. Klumpers D. Darnell M. Bencherif S.A. Weaver J.C. Huebsch N. Lee H.P. Lippens E. Duda G.N. Mooney D.J. Hydrogels with tunable stress relaxation regulate stem cell fate and activity Nat. Mater. 15 2016 326 334 26618884 PMC4767627
  97. [109]Benoit D.S. Schwartz M.P. Durney A.R. Anseth K.S. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells Nat. Mater. 7 2008 816 823 18724374 PMC2929915
  98. [110]Baroli B. From natural bone grafts to tissue engineering therapeutics: brainstorming on pharmaceutical formulative requirements and challenges J. Pharmaceut. Sci. 98 2009 1317 1375 18729202
  99. [111]Short A.R. Koralla D. Deshmukh A. Wissel B. Stocker B. Calhoun M. Dean D. Winter J.O. Hydrogels that allow and facilitate bone repair, remodeling, and regeneration J. Mater. Chem. B 3 2015 7818 7830 26693013 PMC4675359
  100. [112]Chuah Y.J. Peck Y. Lau J.E.J. Heec H.T. Wang D.A. Hydrogel based cartilaginous tissue regeneration: recent insights and technologies Biomater. Sci. 5 2017 613 631 28233881
  101. [114]Yung-Hao T. Khoneisser J. Ping-Chun H. Xiaoyang X. Hydrogel as a bioactive material to regulate stem cell fate Bioact. Mater. (Netherlands) 1 2016 39 55 PMC5883979 29744394
  102. [115]He B. Ou Y.S. Zhou A. Chen S. Zhao W.K. Zhao J.Q. Li H. Zhu Y. Zhao Z.H. Jiang D.M. Functionalized D-form self-assembling peptide hydrogels for bone regeneration Drug Des. Dev. Ther. 10 2016 1379 1388 PMC4833366 27114701
  103. [116]Ni P. Ding Q. Fan M. Liao J. Qian Z. Luo J. Li X. Luo F. Yang Z. Wei Y. Injectable thermosensitive PEG-PCL-PEG hydrogel/acellular bone matrix composite for bone regeneration in cranial defects Biomaterials 35 2014 236 248 24138826
  104. [117]Milani A.H. Freemont A.J. Hoyland J.A. Adlam D.J. Saunders B.R. Injectable doubly cross-linked microgels for improving the mechanical properties of degenerated intervertebral discs Biomacromolecules 13 2012 2793 2801 22877136
  105. [118]Anjum F. Lienemann P.S. Metzger S. Biernaskie J. Kallos M.S. Ehrbar M. Enzyme responsive GAG-based natural-synthetic hybrid hydrogel for tunable growth factor delivery and stem cell differentiation Biomaterials 87 2016 104 117 26914701
  106. [119]Yang F. Wang J. Cao L.Y. Chen R. Tang L.J. Liu C.S. Injectable and redox-responsive hydrogel with adaptive degradation rate for bone regeneration J. Mater. Chem. B 2 2014 295 304 32261508

Cited by

Sorted by citations

Authors
Bai, X., Gao, M., Syed, S., Zhuang, J., Xu, X., & Zhang, X.-Q.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • New Jersey Institute of Technology (US)
Corresponding author
  • Xu, Xiaoyang
  • Zhang, Xue-Qing
ORCID
Venue
Bioactive Materials
Publisher
Elsevier BV
Published
2018-12
Volume
3
Issue
4
Pages
401-417
ISSN
  • 2097-1192 (ISSN-L)
  • 2452-199X
DOI
10.1016/j.bioactmat.2018.05.006
PMC
PMC6038268
OpenAlex
W2806965041
Cited by
556
References
2
Citations by year
2026: 18 · 2025: 60 · 2024: 96 · 2023: 92 · 2022: 86 · 2021: 95 · 2020: 65 · 2019: 36 · 2018: 7
FWCI
4.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioactive Materials (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • New Jersey Institute of Technology (NJIT)
  • New Jersey Health Foundation (PC102-17, PC25-18)
  • NSF Innovation Corps (1723667)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
bioactive hydrogels, bone regeneration, bone defects, polymer scaffolds, hydrogel synthesis, drug delivery methods, calcium phosphate cement, hydroxyapatite, biomaterials

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review