Skip to main content

Advertisement

Log in

Progress of Regenerative Therapy in Orthopedics

  • Regenerative Biology and Medicine in Osteoporosis (T Webster, Section Editor)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To conduct a thorough appraisal of recent and inventive advances in the field of bone tissue engineering using biomaterials, cell-based research, along with the incorporation of biomimetic properties using surface modification of scaffolds.

Recent Findings

This paper will provide an overview on different biomaterials and emerging techniques involved in the fabrication of scaffolds, brief description of signaling pathways involved in osteogenesis, and the effect of surface modification on the fate of progenitor cells.

Summary

The current strategies used for regenerative medicine like cell therapy, gene transfer, and tissue engineering have opened numerous therapeutic avenues for the treatment of various disabling orthopedic disorders. Precise strategy utilized for the reconstruction, restoration, or repair of the bone-related tissues exploits cells, biomaterials, morphogenetic signals, and appropriate mechanical environment to provide the basic constituents required for creating new tissue. Combining all the above strategies in clinical trials would pave the way for successful “bench to bedside” transformation in bone healing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance, ••Of major importance

  1. Black CR, Goriainov V, Gibbs D, Kanczler J, Tare RS, Oreffo RO. Bone tissue engineering. Curr Mol Biol Rep. 2015;1(3):132–40.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Polo-Corrales L, Latorre-Esteves M, Ramirez-Vick JE. Scaffold design for bone regeneration. J Nanosci Nanotechnol. 2014;14(1):15–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mackie E, Ahmed Y, Tatarczuch L, Chen K-S, Mirams M. Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol. 2008;40(1):46–62.

    Article  CAS  PubMed  Google Scholar 

  4. Soltanoff CS, Chen W, Yang S, Li Y-P. Signaling networks that control the lineage commitment and differentiation of bone cells. Crit Rev Eukaryot Gene Expr. 2009;19(1):1–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yu X, Tang X, Gohil SV, Laurencin CT. Biomaterials for bone regenerative engineering. Adv Healthc Mater. 2015;4(9):1268–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. O’brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today. 2011;14(3):88–95.

    Article  CAS  Google Scholar 

  7. Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng. 2012;40(5):363–408.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ferreira AM, Gentile P, Chiono V, Ciardelli G. Collagen for bone tissue regeneration. Acta Biomater. 2012;8(9):3191–200.

    Article  CAS  PubMed  Google Scholar 

  9. Titorencu I, Georgiana Albu M, Nemecz M, Jinga V. Natural polymer-cell bioconstructs for bone tissue engineering. Curr Stem Cell Res Ther. 2017;12(2):165–74.

    Article  CAS  PubMed  Google Scholar 

  10. Liu X, Ma PX. Polymeric scaffolds for bone Tissue Eng 2004.

  11. Bose S, Roy M, Bandyopadhyay A. Recent advances in bone tissue engineering scaffolds. Trends Biotechnol. 2012;30(10):546–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Alvarez K, Nakajima H. Metallic scaffolds for bone regeneration. Materials. 2009;2(3):790–832.

    Article  CAS  PubMed Central  Google Scholar 

  13. Matassi F, Nistri L, Paez DC, Innocenti M. New biomaterials for bone regeneration. Clinical cases in mineral and bone. Metabolism. 2011;8(1):21.

    Google Scholar 

  14. Tanner K. Bioactive composites for bone tissue engineering. Proc Inst Mech Eng H J Eng Med. 2010;224(12):1359–72.

    Article  CAS  Google Scholar 

  15. Boccaccini AR, Blaker JJ. Bioactive composite materials for tissue engineering scaffolds. Expert Rev Med Devices. 2005;2(3):303–17.

    Article  CAS  PubMed  Google Scholar 

  16. Mano JF, Sousa RA, Boesel LF, Neves NM, Reis RL. Bioinert, biodegradable and injectable polymeric matrix composites for hard tissue replacement: state of the art and recent developments. Compos Sci Technol. 2004;64(6):789–817.

    Article  CAS  Google Scholar 

  17. Wang M. Composite scaffolds for bone tissue engineering. Am J Biochem Biotechnol 2006.

  18. Chen Q, Zhu C, Thouas GA. Progress and challenges in biomaterials used for bone tissue engineering: bioactive glasses and elastomeric composites. Progress Biomater. 2012;1(1):2.

    Article  Google Scholar 

  19. Navarro M, Michiardi A, Castano O, Planell J. Biomaterials in orthopaedics. J R Soc Interface. 2008;5(27):1137–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Coombes A, Meikle M. Resorbable synthetic polymers s replacements for bone graft. Clin Mater. 1994;17(1):35–67.

    Article  CAS  PubMed  Google Scholar 

  21. Samavedi S, Whittington AR, Goldstein AS. Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater. 2013;9(9):8037–45.

    Article  CAS  PubMed  Google Scholar 

  22. Srinivasan K, Naula DP, Mijares DQ, Janal MN, LeGeros RZ, Zhang Y. Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats. J Biomed Mater Res A. 2016;104(7):1622–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Radha R, Sreekanth D. Insight of magnesium alloys and composites for orthopedic implant applications—a review. J Magnes Alloys. 2017;5:286–312.

    Article  CAS  Google Scholar 

  24. Prasad A, Sankar MR, Katiyar V. State of art on solvent casting particulate leaching method for orthopedic scaffoldsfabrication. Materials Today: Proceedings. 2017;4(2):898–907.

    Article  Google Scholar 

  25. Lv Q, Feng Q. Preparation of 3-D regenerated fibroin scaffolds with freeze drying method and freeze drying/foaming technique. J Mater Sci Mater Med. 2006;17(12):1349–56.

    Article  CAS  PubMed  Google Scholar 

  26. Roseti L, Parisi V, Petretta M, Cavallo C, Desando G, Bartolotti I, et al. Scaffolds for bone tissue engineering: state of the art and new perspectives. Mater Sci Eng C. 2017;78:1246–62.

    Article  CAS  Google Scholar 

  27. Cirllo V, Guarino V, Ambrosio L. Design of bioactive electrospun scaffolds for bone tissue engineering. J Appl Biomater Funct Mater. 2012;10(3)

  28. • Wen Y, Xun S, Haoye M, Baichuan S, Peng C, Xuejian L, et al. 3D printed porous ceramic scaffolds for bone tissue engineering: a review. Biomater Sci. 2017;5(9):1690–8. Influence 3D-printed ceramic scaffold was evaluated.

    Article  CAS  PubMed  Google Scholar 

  29. Yang J, Wang J, Yuan T, Zhu X, Xiang Z, Fan Y, et al. The enhanced effect of surface microstructured porous titanium on adhesion and osteoblastic differentiation of mesenchymal stem cells. J Mater Sci Mater Med. 2013;24(9):2235–46.

    Article  CAS  PubMed  Google Scholar 

  30. Do AV, Khorsand B, Geary SM, Salem AK. 3D printing of scaffolds for tissue regeneration applications. Adv Healthc Mater. 2015;4(12):1742–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wu G-H, Hsu S-H. Polymeric-based 3D printing for tissue engineering. J Med Biol Eng. 2015;35(3):285–92.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Stegen S, van Gastel N, Carmeliet G. Bringing new life to damaged bone: the importance of angiogenesis in bone repair and regeneration. Bone. 2015;70:19–27.

    Article  CAS  PubMed  Google Scholar 

  33. Hasan A, Paul A, Vrana NE, Zhao X, Memic A, Hwang Y-S, et al. Microfluidic techniques for development of 3D vascularized tissue. Biomaterials. 2014;35(26):7308–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hadjipanayi E, Schilling AF. Hypoxia-based strategies for angiogenic induction: the dawn of a new era for ischemia therapy and tissue regeneration. Organ. 2013;9(4):261–72.

    Google Scholar 

  35. Yavropoulou M, Yovos J. The molecular basis of bone mechanotransduction. J Musculoskelet Neuronal Interact. 2016;16(3):221–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Ramirez-Vick JE. Biophysical stimulation for bone regeneration. JSM Biotechnol Biomed Eng. 2013;1(2):1014.

    PubMed  PubMed Central  Google Scholar 

  37. Victoria G, Petrisor B, Drew B, Dick D. Bone stimulation for fracture healing: what’s all the fuss? Indian J Orthop. 2009;43(2):117–20.

    Article  PubMed  PubMed Central  Google Scholar 

  38. •• Yong Y, Ming ZD, Feng L, Chun ZW, Hua W. Electromagnetic fields promote osteogenesis of rat mesenchymal stem cells through the PKA and ERK1/2 pathways. Journal of tissue engineering and regenerative medicine. 2016;10(10). EMF was able to influence the fate of progenitor cells.

  39. Huang W, Yang S, Shao J, Li Y-P. Signaling and transcriptional regulation in osteoblast commitment and differentiation. Frontiers in bioscience: a journal and virtual Library. 2007;12:3068.

    Article  CAS  Google Scholar 

  40. Zhang C. Transcriptional regulation of bone formation by the osteoblast-specific transcription factor Osx. J Orthop Surg Res. 2010;5(1):37.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Chen LF. Tumor suppressor function of RUNX3 in breast cancer. J Cell Biochem. 2012;113(5):1470–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. 2005;8(5):727–38. https://doi.org/10.1016/j.devcel.2005.02.013.

    Article  CAS  PubMed  Google Scholar 

  43. Yuan Z, Li Q, Luo S, Liu Z, Luo D, Zhang B, et al. PPARγ and Wnt signaling in adipogenic and osteogenic differentiation of mesenchymal stem cells. Curr Stem Cell Res Ther. 2016;11(3):216–25.

    Article  CAS  PubMed  Google Scholar 

  44. Glass DA, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005;8(5):751–64.

    Article  CAS  PubMed  Google Scholar 

  45. Suzuki A, Guicheux J, Palmer G, Miura Y, Oiso Y, Bonjour J-P, et al. Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation. Bone. 2002;30(1):91–8.

    Article  CAS  PubMed  Google Scholar 

  46. Ge C, Xiao G, Jiang D, Yang Q, Hatch NE, Roca H, et al. Identification and functional characterization of ERK/MAPK phosphorylation sites in the Runx2 transcription factor. J Biol Chem. 2009;284(47):32533–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Chen Z, Luo Q, Lin C, Kuang D, Song G. Simulated microgravity inhibits osteogenic differentiation of mesenchymal stem cells via depolymerizing F-actin to impede TAZ nuclear translocation. Sci Rep 2016;6.

  48. Marie P. Fibroblast growth factor signaling controlling osteoblast differentiation. Gene. 2003;316:23–32.

    Article  CAS  PubMed  Google Scholar 

  49. Su N, Jin M, Chen L. Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models. Bone research. 2014;2:14003.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Miao D, He B, Karaplis AC, Goltzman D. Parathyroid hormone is essential for normal fetal bone formation. J Clin Invest. 2002;109(9):1173–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mihai R, Farndon J. Parathyroid disease and calcium metabolism. Br J Anaesth. 2000;85(1):29–43.

    Article  CAS  PubMed  Google Scholar 

  52. Pinheiro PL, Cardoso JC, Power DM, Canário AV. Functional characterization and evolution of PTH/PTHrP receptors: insights from the chicken. BMC Evol Biol. 2012;12(1):110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lupp A, Klenk C, Röcken C, Evert M, Mawrin C, Schulz S. Immunohistochemical identification of the PTHR1 parathyroid hormone receptor in normal and neoplastic human tissues. Eur J Endocrinol. 2010;162(5):979–86.

    Article  CAS  PubMed  Google Scholar 

  54. Greenspan SL, Bone HG, Ettinger MP, Hanley DA, Lindsay R, Zanchetta JR, et al. Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial treatment of postmenopausal osteoporotic women with parathyroid hormone (1-84). Ann Intern Med. 2007;146(5):326–39.

    Article  PubMed  Google Scholar 

  55. Sone T, Fukunaga M, Ono S, Nishiyama T. A small dose of human parathyroid hormone (1-34) increased bone mass in the lumbar vertebrae in patients with senile osteoporosis. Miner Electrolyte Metab. 1994;21(1–3):232–5.

    Google Scholar 

  56. Ma YL, Cain RL, Halladay DL, Yang X, Zeng Q, Miles RR, et al. Catabolic effects of continuous human PTH (1–38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation. Endocrinology. 2001;142(9):4047–54.

    Article  CAS  PubMed  Google Scholar 

  57. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89(5):755–64.

    Article  CAS  PubMed  Google Scholar 

  58. Åberg T, Cavender A, Gaikwad JS, Bronckers AL, Wang X, Waltimo-Sirén J, et al. Phenotypic changes in dentition of Runx2 homozygote-null mutant mice. J Histochem Cytochem. 2004;52(1):131–9.

    Article  PubMed  Google Scholar 

  59. Jena N, Martı́n-Seisdedos C, McCue P, Croce CM. BMP7 null mutation in mice: developmental defects in skeleton, kidney, and eye. Exp Cell Res. 1997;230(1):28–37.

    Article  CAS  PubMed  Google Scholar 

  60. Tseng Y-H, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature. 2008;454(7207):1000–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kim RY, Robertson EJ, Solloway MJ. Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Dev Biol. 2001;235(2):449–66.

    Article  CAS  PubMed  Google Scholar 

  62. Dudley AT, Robertson EJ. Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Dev Dyn. 1997;208(3):349–62.

    Article  CAS  PubMed  Google Scholar 

  63. Katagiri T, Boorla S, Frendo J-L, Hogan BL, Karsenty G. Skeletal abnormalities in doubly heterozygous Bmp4 and Bmp7 mice. Dev Genet. 1998;22(4):340–8.

    Article  CAS  PubMed  Google Scholar 

  64. Chen D, Harris M, Rossini G, Dunstan C, Dallas S, Feng J, et al. Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in culturesof fetal rat calvarial osteoblasts. Calcif Tissue Int. 1997;60(3):283–90.

    Article  CAS  PubMed  Google Scholar 

  65. Ma L, Lu M-F, Schwartz RJ, Martin JF. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development. 2005;132(24):5601–11.

    Article  CAS  PubMed  Google Scholar 

  66. Wang E, Israel D, Kelly S, Luxenberg D. Bone morphogenetic protein-2 causes commitment and differentiation in C3Hl0T1/2 and 3T3 cells. Growth Factors. 1993;9(1):57–71.

    Article  CAS  PubMed  Google Scholar 

  67. Sumanasinghe RD, Bernacki SH, Loboa EG. Osteogenic differentiation of human mesenchymal stem cells in collagen matrices: effect of uniaxial cyclic tensile strain on bone morphogenetic protein (BMP-2) mRNA expression. Tissue Eng. 2006;12(12):3459–65.

    Article  CAS  PubMed  Google Scholar 

  68. Lieberman JR, Le LQ, Wu L, Finerman GA, Berk A, Witte ON, et al. Regional gene therapy with a BMP-2-producing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents. J Orthop Res. 1998;16(3):330–9.

    Article  CAS  PubMed  Google Scholar 

  69. Yamamoto N, Akiyama S, Katagiri T, Namiki M, Kurokawa T, Suda T. Smad1 and smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts. Biochem Biophys Res Commun. 1997;238(2):574–80.

    Article  CAS  PubMed  Google Scholar 

  70. Chang H, Huylebroeck D, Verschueren K, Guo Q, Matzuk MM, Zwijsen A. Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development. 1999;126(8):1631–42.

    CAS  PubMed  Google Scholar 

  71. Denhardt DT, Noda M, O’Regan AW, Pavlin D, Berman JS. Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Investig. 2001;107(9):1055–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C et al. Increased bone formation in osteocalcin-deficient mice. 1996.

  73. Patterson-Buckendahl P, Sowinska A, Yee S, Patel D, Pagkalinawan S, Shahid M, et al. Decreased sensory responses in osteocalcin null mutant mice imply neuropeptide function. Cell Mol Neurobiol. 2012;32(5):879–89.

    Article  CAS  PubMed  Google Scholar 

  74. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108(1):17–29.

    Article  CAS  PubMed  Google Scholar 

  75. Samee N, Geoffroy V, Marty C, Schiltz C, Vieux-Rochas M, Levi G, et al. Dlx5, a positive regulator of osteoblastogenesis, is essential for osteoblast-osteoclast coupling. Am J Pathol. 2008;173(3):773–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Karaplis AC, Luz A, Glowacki J, Bronson RT, Tybulewicz V, Kronenberg HM, et al. Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev. 1994;8(3):277–89.

    Article  CAS  PubMed  Google Scholar 

  77. Miao D, He B, Lanske B, Bai X-Y, Tong X-K, Hendy GN, et al. Skeletal abnormalities in Pth-null mice are influenced by dietary calcium. Endocrinology. 2004;145(4):2046–53.

    Article  CAS  PubMed  Google Scholar 

  78. Datta NS, Abou-Samra AB. PTH and PTHrP signaling in osteoblasts. Cell Signal. 2009;21(8):1245–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Qiu T, Wu X, Zhang F, Clemens TL, Wan M, Cao X. TGF-β type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling. Nat Cell Biol. 2010;12(3):224–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Greenblatt MB, Shim J-H, Zou W, Sitara D, Schweitzer M, Hu D, et al. The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice. J Clin Invest. 2010;120(7):2457–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Chang J, Liu F, Lee M, Wu B, Ting K, Zara JN, et al. NF-κB inhibits osteogenic differentiation of mesenchymal stem cells by promoting β-catenin degradation. Proc Natl Acad Sci. 2013;110(23):9469–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Gilbert L, He X, Farmer P, Rubin J, Drissi H, Van Wijnen AJ, et al. Expression of the osteoblast differentiation factor RUNX2 (Cbfa1/AML3/Pebp2αA) is inhibited by tumor necrosis factor-α. J Biol Chem. 2002;277(4):2695–701.

    Article  CAS  PubMed  Google Scholar 

  83. Tarapore RS, Lim J, Tian C, Pacios S, Xiao W, Reid D, et al. NF-κB has a direct role in inhibiting Bmp-and Wnt-induced matrix protein expression. J Bone Miner Res. 2016;31(1):52–64.

    Article  CAS  PubMed  Google Scholar 

  84. Hie M, Tsukamoto I. Increased expression of the receptor for activation of NF-κB and decreased runt-related transcription factor 2 expression in bone of rats with streptozotocin-induced diabetes. Int J Mol Med. 2010;26(4):611–8.

    CAS  PubMed  Google Scholar 

  85. Lacefield WR. Materials characteristics of uncoated/ceramic-coated implant materials. Adv Dent Res. 1999;13(1):21–6.

    Article  CAS  PubMed  Google Scholar 

  86. •• Hwang J-H, Lee D-H, Byun MR, Kim AR, Kim KM, Park JI, et al. Nanotopological plate stimulates osteogenic differentiation through TAZ activation. Sci Rep. 2017;7(1):3632. Pathway through which topology influences osteogenesis.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Boyan BD, Hummert TW, Dean DD, Schwartz Z. Role of material surfaces in regulating bone and cartilage cell response. Biomaterials. 1996;17(2):137–46.

    Article  CAS  PubMed  Google Scholar 

  88. Gittens RA, Olivares-Navarrete R, McLachlan T, Cai Y, Hyzy SL, Schneider JM, et al. Differential responses of osteoblast lineage cells to nanotopographically-modified, microroughened titanium–aluminum–vanadium alloy surfaces. Biomaterials. 2012;33(35):8986–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Datta N, Holtorf HL, Sikavitsas VI, Jansen JA, Mikos AG. Effect of bone extracellular matrix synthesized in vitro on the osteoblastic differentiation of marrow stromal cells. Biomaterials. 2005;26(9):971–7.

    Article  CAS  PubMed  Google Scholar 

  90. Cheng A, Cohen DJ, Boyan BD, Schwartz Z. Laser-sintered constructs with bio-inspired porosity and surface micro/nano-roughness enhance mesenchymal stem cell differentiation and matrix mineralization in vitro. Calcif Tissue Int. 2016;99(6):625–37.

    Article  CAS  PubMed  Google Scholar 

  91. Chen W, Tian B, Lei Y, Ke Q-F, Zhu Z-A, Guo Y-P. Hydroxyapatite coatings with oriented nanoplate and nanorod arrays: fabrication, morphology, cytocompatibility and osteogenic differentiation. Mater Sci Eng C. 2016;67:395–408.

    Article  CAS  Google Scholar 

  92. Olivares-Navarrete R, Raines AL, Hyzy SL, Park JH, Hutton DL, Cochran DL, et al. Osteoblast maturation and new bone formation in response to titanium implant surface features are reduced with age. J Bone Miner Res. 2012;27(8):1773–83.

    Article  PubMed  Google Scholar 

  93. Olivares-Navarrete R, Hyzy SL, Park JH, Dunn GR, Haithcock DA, Wasilewski CE, et al. Mediation of osteogenic differentiation of human mesenchymal stem cells on titanium surfaces by a Wnt-integrin feedback loop. Biomaterials. 2011;32(27):6399–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Gomes ME, Holtorf HL, Reis RL, Mikos AG. Influence of the porosity of starch-based fiber mesh scaffolds on the proliferation and osteogenic differentiation of bone marrow stromal cells cultured in a flow perfusion bioreactor. Tissue Eng. 2006;12(4):801–9.

    Article  CAS  PubMed  Google Scholar 

  95. Faghihi F, Eslaminejad MB, Nekookar A, Najar M, Salekdeh G. The effect of purmorphamine and sirolimus on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Biomed Pharmacother. 2013;67(1):31–8.

    Article  CAS  PubMed  Google Scholar 

  96. Park KW, Waki H, Kim W-K, Davies BS, Young SG, Parhami F, et al. The small molecule phenamil induces osteoblast differentiation and mineralization. Mol Cell Biol. 2009;29(14):3905–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Yu W-L, Sun T-W, Qi C, Zhao H-K, Ding Z-Y, Zhang Z-W, et al. Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration. Sci Rep. 2017;7:srep44129.

    Article  CAS  Google Scholar 

  98. Park S-J, Lee KW, Lim D-S, Lee S. The sulfated polysaccharide fucoidan stimulates osteogenic differentiation of human adipose-derived stem cells. Stem Cells Dev. 2011;21(12):2204–11.

    Article  PubMed  CAS  Google Scholar 

  99. • Du K, Li Z, Fang X, Cao T, Xu Y. Ferulic acid promotes osteogenesis of bone marrow-derived mesenchymal stem cells by inhibiting microRNA-340 to induce β-catenin expression through hypoxia. Eur J Cell Biol. 2017;96(6):496–503. Targeted osteogenesis using ferulic acid and its signaling pathway.

    Article  CAS  PubMed  Google Scholar 

  100. Rogina A, Antunović M, Pribolšan L, Caput Mihalić K, Vukasović A, Ivković A, et al. Human mesenchymal stem cells differentiation regulated by hydroxyapatite content within chitosan-based scaffolds under perfusion conditions. Polymers. 2017;9(9):387.

    Article  CAS  Google Scholar 

  101. Huan Z, Chang J. Novel bioactive composite bone cements based on the β-tricalcium phosphate–monocalcium phosphate monohydrate composite cement system. Acta Biomater. 2009;5(4):1253–64.

    Article  CAS  PubMed  Google Scholar 

  102. Bohner M. Design of ceramic-based cements and putties for bone graft substitution. Eur Cell Mater. 2010;20(1):3–10.

    Google Scholar 

  103. Shelton R, Liu Y, Cooper P, Gbureck U, German M, Barralet J. Bone marrow cell gene expression and tissue construct assembly using octacalcium phosphate microscaffolds. Biomaterials. 2006;27(14):2874–81.

    Article  CAS  PubMed  Google Scholar 

  104. Harris C, Cooper L. Comparison of bone graft matrices for human mesenchymal stem cell-directed osteogenesis. J Biomed Mater Res A. 2004;68(4):747–55.

    Article  CAS  PubMed  Google Scholar 

  105. Kon E, Muraglia A, Corsi A, Bianco P, Marcacci M, Martin I, et al. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res. 2000;49(3):328–37.

    Article  CAS  PubMed  Google Scholar 

  106. Kasten P, Luginbühl R, Van Griensven M, Barkhausen T, Krettek C, Bohner M, et al. Comparison of human bone marrow stromal cells seeded on calcium-deficient hydroxyapatite, β-tricalcium phosphate and demineralized bone matrix. Biomaterials. 2003;24(15):2593–603.

    Article  CAS  PubMed  Google Scholar 

  107. Henkel J, Woodruff MA, Epari DR, Steck R, Glatt V, Dickinson IC, et al. Bone regeneration based on tissue engineering conceptions—a 21st century perspective. Bone Res. 2013;1(3):216–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. • Dong L, Wang S-J, Zhao X-R, Zhu Y-F, Yu J-K. 3D-printed poly (ε-caprolactone) scaffold integrated with cell-laden chitosan hydrogels for bone tissue engineering. Sci Rep. 2017;7(1):13412. Novel cell-based hydrogel scaffolds.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Zheng P, Yao Q, Mao F, Liu N, Xu Y, Wei B, et al. Adhesion, proliferation and osteogenic differentiation of mesenchymal stem cells in 3D printed poly-ε-caprolactone/hydroxyapatite scaffolds combined with bone marrow clots. Mol Med Rep. 2017;16(4):5078–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Murphy C, Kolan K, Li W, Semon J, Day D, Leu M. 3D bioprinting of stem cells and polymer/bioactive glass composite scaffolds for bone tissue engineering. International Journal of Bioprinting. 2017;3(1):1–11.

    Article  Google Scholar 

  111. Qi X, Pei P, Zhu M, Du X, Xin C, Zhao S, et al. Three dimensional printing of calcium sulfate and mesoporous bioactive glass scaffolds for improving bone regeneration in vitro and in vivo. Sci Rep. 2017;7:42556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Barbeck M, Serra T, Booms P, Stojanovic S, Najman S, Engel E, et al. Analysis of the in vitro degradation and the in vivo tissue response to bi-layered 3D-printed scaffolds combining PLA and biphasic PLA/bioglass components—guidance of the inflammatory response as basis for osteochondral regeneration. Bioactive Mater. 2017;2:208–23.

    Article  Google Scholar 

  113. Kanthan S, Kavitha G, Addi S, Choon D, Kamarul T. Platelet-rich plasma (PRP) enhances bone healing in non-united critical-sized defects: a preliminary study involving rabbit models. Injury. 2011;42(8):782–9.

    Article  CAS  PubMed  Google Scholar 

  114. Latalski M, Elbatrawy YA, Thabet AM, Gregosiewicz A, Raganowicz T, Fatyga M. Enhancing bone healing during distraction osteogenesis with platelet-rich plasma. Injury. 2011;42(8):821–4.

    Article  PubMed  Google Scholar 

  115. • Mcgoldrick R, Chattopadhyay A, Crowe C, Chiou G, Hui K, Farnebo S et al. The tissue engineered tendon bone Interface: in vitro and in vivo synergistic effects of adipo-derived stem cells, platelet rich plasma and extracellular matrix hydrogel. Plast Reconstr Surg. 2017. PRP and extracellular matrix hydrogel promote bone repair.

Download references

Acknowledgements

The authors thank A. Revathi for carefully proof-reading the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Geetha Manivasagam or Dwaipayan Sen.

Ethics declarations

Conflict of Interest

Pearlin, Sunita Nayak, Geetha Manivasgam and Dwaipayan Sen declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Regenerative Biology and Medicine in Osteoporosis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pearlin, Nayak, S., Manivasagam, G. et al. Progress of Regenerative Therapy in Orthopedics. Curr Osteoporos Rep 16, 169–181 (2018). https://doi.org/10.1007/s11914-018-0428-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-018-0428-x

Keywords

Navigation