Marrow Stimulation and Augmentation

  • Michael L. Redondo
  • Brian R. Waterman
  • Jack M. Bert
  • Brian J. ColeEmail author


Hyaline cartilage is an essential component for the form and function of articulating joints, such as the knee. With the annual incidence on the rise, there are between an estimated 30,000 and 100,000 chondral repair procedures that are performed yearly in the United States. Marrow stimulation is a commonly used technique for articular cartilage repair. Marrow stimulation involves the perforation of the subchondral bone plate, most commonly with an arthroscopic microfracture awl, for the release of marrow elements. The marrow elements fill the articular cartilage defect forming a fibrocartilage repair. Though arthroscopic microfracture is considered by some as the gold standard therapy for cartilage repair, short-term outcomes have been shown to be unreliable and unsustainable. Some experts now opine that marrow stimulation as it currently exists should be outright abandoned.

Recently, however, there has been a push for new innovations in the augmentation of the marrow stimulation techniques in order to attain more sustainable outcomes and decrease associated complications. The augmentation of microfracture via the addition of post-microfracture intra-articular platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and adipose-derived stem cells (ASCs) is an exciting advancement in marrow stimulation. Also, the recent introduction of the nanofracture, “rebirth” of drilling, and BioCartilage techniques offer promising technological advancement in the field of marrow stimulation. This chapter focuses on clinical indications, surgical technique, and the outcomes of marrow stimulation procedures and the augmentation of these procedures.


Marrow stimulation Cartilage restoration Biologics Microfracture Platelet-rich plasma Bone marrow aspirate concentrate Adipose-derived mesenchymal stem cells Subchondral drilling 


  1. 1.
    Dowthwaite G, Bishop J, Redman S, et al. The surface of articular cartilage contains a progenitor cell population. J Cell Sci. 2004;117(6):889–97. Scholar
  2. 2.
    Alford JW. Cartilage restoration, Part 1: basic science, historical perspective, patient evaluation, and treatment options. Am J Sports Med. 2005;33(2):295–306. Scholar
  3. 3.
    Richter DL, Tanksley JA, Miller MD. Osteochondral autograft transplantation: a review of the surgical technique and outcomes. Sports Med Arthrosc Rev. 2016;24(2):74–8. Scholar
  4. 4.
    Montgomery SR, Foster BD, Ngo SS, et al. Trends in the surgical treatment of articular cartilage defects of the knee in the United States. Knee Surg Sports Traumatol Arthrosc. 2014;22(9):2070–5. Scholar
  5. 5.
    McCormick F, Harris JD, Abrams GD, et al. Trends in the surgical treatment of articular cartilage lesions in the United States: an analysis of a large private-payer database over a period of 8 years. Arthrosc – J Arthrosc Relat Surg. 2014;30(2):222–6. Scholar
  6. 6.
    Aroen A, Loken S, Heir S, et al. Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sport Med. 2004;32(1):211–5. Scholar
  7. 7.
    Ciccotti MC, Kraeutler MJ, Austin LS, et al. The prevalence of articular cartilage changes in the knee joint in patients undergoing arthroscopy for meniscal pathology. Arthrosc – J Arthrosc Relat Surg. 2012;28(10):1437–44. Scholar
  8. 8.
    Steinwachs MR, Guggi T, Kreuz PC. Marrow stimulation techniques. Injury. 2008;39(1 SUPPL):26–31. Scholar
  9. 9.
    Brady K, Dickinson SC, Hollander AP. Changes in chondrogenic progenitor populations associated with aging and osteoarthritis. Cartilage. 2015;6(2 Suppl):30S–5S. Scholar
  10. 10.
    Erickson IE, Van Veen SC, Sengupta S, Kestle SR, Mauck RL. Cartilage matrix formation by bovine mesenchymal stem cells in three-dimensional culture is age-dependent. Clin Orthop Relat Res. 2011;469:2744–53. Scholar
  11. 11.
    Filardo G, Perdisa F, Roffi A, Marcacci M, Kon E. Stem cells in articular cartilage regeneration. J Orthop Surg Res. 2016;11:42. Scholar
  12. 12.
    Madry H, Gao L, Eichler H, Orth P, Cucchiarini M. Bone marrow aspirate concentrate-enhanced marrow stimulation of chondral defects. Stem Cells Int. 2017;2017.
  13. 13.
    Ficat RP, Ficat C, Gedeon P, Toussaint JB. Spongialization: a new treatment for diseased patellae. Clin Orthop Relat Res. 1979;144:74–83. Google Scholar
  14. 14.
    Johnson LL. Arthroscopic abrasion arthroplasty historical and pathologic perspective: present status. Arthroscopy. 1986;2(1):54–69. Scholar
  15. 15.
    Bert JM. Abandoning microfracture of the knee: has the time come? Arthroscopy. 2015;31(3):501–5. Scholar
  16. 16.
    Rand JA. Role of arthroscopy in osteoarthritis of the knee. Arthrosc J Arthrosc Relat Surg. 1991;7(4):358–63. Scholar
  17. 17.
    Sansone V, de Girolamo L, Pascale W, Melato M, Pascale V. Long-term results of abrasion arthroplasty for full-thickness cartilage lesions of the medial femoral condyle. Arthroscopy. 2015;31(3):396–403. Scholar
  18. 18.
    Steadman JR, Miller BS, Karas SG, Schlegel TF, Briggs KK, Hawkins RJ. The microfracture technique in the treatment of full-thickness chondral lesions of the knee in National Football League players. J Knee Surg. 2003;16(2):83–6. Accessed August 17, 2017.PubMedGoogle Scholar
  19. 19.
    Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sport Med. 2009;37(10):2053–63. Scholar
  20. 20.
    Erggelet C, Vavken P. Microfracture for the treatment of cartilage defects in the knee joint – a golden standard? J Clin Orthop Trauma. 2016;7(3):145–52. Scholar
  21. 21.
    Eldracher M, Orth P, Cucchiarini M, Pape D, Madry H. Small subchondral drill holes improve marrow stimulation of articular cartilage defects. Am J Sports Med. 2014;42(11):2741–50. Scholar
  22. 22.
    Gianakos AL, Yasui Y, Fraser EJ, et al. The effect of different bone marrow stimulation techniques on human talar subchondral bone: a micro–computed tomography evaluation. Arthrosc – J Arthrosc Relat Surg. 2016;32(10):2110–7. Scholar
  23. 23.
    Chen H, Sun J, Hoemann CD, et al. Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair. J Orthop Res. 2009;27(11):1432–8. Scholar
  24. 24.
    Chen H, Hoemann CD, Sun J, et al. Depth of subchondral perforation influences the outcome of bone marrow stimulation cartilage repair. J Orthop Res. 2011;29(8):1178–84. Scholar
  25. 25.
    Lee YHD, Suzer F, Thermann H. Autologous matrix-induced chondrogenesis in the knee. Cartilage. 2014;5(3):145–53. Scholar
  26. 26.
    Kreuz PC, Steinwachs MR, Erggelet C, et al. Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthr Cartil. 2006;14(11):1119–25. Scholar
  27. 27.
    Frisbie DD, Trotter GW, Powers BE, et al. Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses. Vet Surg. 1999;28(4):242–55. Scholar
  28. 28.
    Demange MK, Minas T, von Keudell A, Sodha S, Bryant T, Gomoll AH. Intralesional osteophyte regrowth following autologous chondrocyte implantation after previous treatment with marrow stimulation technique. Cartilage. 2017;8(2):131–8. Scholar
  29. 29.
    Cole BJ, Farr J, Winalski CS, et al. Outcomes after a single-stage procedure for cell-based cartilage repair a prospective clinical safety trial with 2-year follow-up. Am J Sports Med. 2011;39(6):1170–9. Scholar
  30. 30.
    Orth P, Goebel L, Wolfram U, et al. Effect of subchondral drilling on the microarchitecture of subchondral bone. Am J Sports Med. 2012;40(4):828–36. Scholar
  31. 31.
    Beck A, Murphy DJ, Carey-Smith R, Wood DJ, Zheng MH. Treatment of articular cartilage defects with microfracture and autologous matrix-induced chondrogenesis leads to extensive subchondral bone cyst formation in a sheep model. Am J Sports Med. 2016:363546516652619.
  32. 32.
    Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG. Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthrosc – J Arthrosc Relat Surg. 2003;19(5):477–84. Scholar
  33. 33.
    Gobbi A, Nunag P, Malinowski K. Treatment of full thickness chondral lesions of the knee with microfracture in a group of athletes. Knee Surg Sports Traumatol Arthrosc. 2005;13(3):213–21. Scholar
  34. 34.
    Steadman J, Hanson C, Briggs K, Matheny L, James E, Guillet A. Outcomes after knee microfracture of chondral defects in alpine ski racers. J Knee Surg. 2014;27(5):407–10. Scholar
  35. 35.
    Scillia AJ, Aune KT, Andrachuk JS, et al. Return to play after chondroplasty of the knee in national football league athletes. Am J Sports Med. 2015;43(3):663–8. Scholar
  36. 36.
    Cerynik DL, Lewullis GE, Joves BC, Palmer MP, Tom JA. Outcomes of microfracture in professional basketball players. Knee Surg Sports Traumatol Arthrosc. 2009;17(9):1135–9. Scholar
  37. 37.
    Namdari S, Baldwin K, Anakwenze O, Park M-J, Huffman GR, Sennett BJ. Results and performance after microfracture in national basketball association athletes. Am J Sports Med. 2009;37(5):943–8. Scholar
  38. 38.
    Gudas R, Kalesinskas RJ, Kimtys V, et al. A prospective randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint in young athletes. Arthrosc – J Arthrosc Relat Surg. 2005;21(9):1066–75. Scholar
  39. 39.
    Gudas R, Gudaitė A, Pocius A, et al. Ten-year follow-up of a prospective, randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint of athletes. Am J Sports Med. 2012;40(11):2499–508. Scholar
  40. 40.
    Harris JD, Brophy RH, Siston RA, Flanigan DC. Treatment of chondral defects in the athlete’s knee. Arthroscopy. 2010;26(6):841–52. Scholar
  41. 41.
    Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015;16(1):321. Scholar
  42. 42.
    Strauss EJ, Barker JU, Kercher JS, Cole BJ, Mithoefer K. Augmentation strategies following the microfracture technique for repair of focal chondral defects. Cartilage. 2010;1(2):145–52. Scholar
  43. 43.
    Miyakoshi N, Kobayashi M, Nozaka K, Okada K, Shimada Y, Itoi E. Effects of intraarticular administration of basic fibroblast growth factor with hyaluronic acid on osteochondral defects of the knee in rabbits. Arch Orthop Trauma Surg. 2005;125(10):683–92. Scholar
  44. 44.
    Gunes T, Bostan B, Erdem M, Koseoglu RD, Asci M, Sen C. Intraarticular hyaluronic acid injection after microfracture technique for the management of full-thickness cartilage defects does not improve the quality of repair tissue. Cartilage. 2012;3(1):20–6. Scholar
  45. 45.
    Doral MN, Bilge O, Batmaz G, et al. Treatment of osteochondral lesions of the talus with microfracture technique and postoperative hyaluronan injection. Knee Surg Sport Traumatol Arthrosc. 2012;20(7):1398–403. Scholar
  46. 46.
    Shang XL, Tao HY, Chen SY, Li YX, Hua YH. Clinical and MRI outcomes of HA injection following arthroscopic microfracture for osteochondral lesions of the talus. Knee Surg Sport Traumatol Arthrosc. 2016;24(4):1243–9. Scholar
  47. 47.
    Abrams GD, Frank RM, Fortier LA, Cole BJ. Platelet-rich plasma for articular cartilage repair. Sports Med Arthrosc. 2013;21(4):213–9. Scholar
  48. 48.
    Mascarenhas R, Saltzman BM, Fortier LA, Cole BJ. Role of platelet-rich plasma in articular cartilage injury and disease. J Knee Surg. 2015;28(1):3–10. Scholar
  49. 49.
    Laver L, Marom N, Dnyanesh L, Mei-Dan O, Espregueira-Mendes J, Gobbi A. PRP for degenerative cartilage disease. Cartilage. 2016:194760351667070.
  50. 50.
    Krüger JP, Hondke S, Endres M, Pruss A, Siclari A, Kaps C. Human platelet-rich plasma stimulates migration and chondrogenic differentiation of human subchondral progenitor cells. J Orthop Res. 2012;30(6):845–52. Scholar
  51. 51.
    Mancò A, Goderecci R, Rughetti A, et al. Microfracture versus microfracture and platelet-rich plasma: arthroscopic treatment of knee chondral lesions. A two-year follow-up study. Joints. 2016;4(3):142–7. Scholar
  52. 52.
    Manunta AF, Manconi A. The treatment of chondral lesions of the knee with the microfracture technique and platelet-rich plasma. Joints. 2013;1(4):167–70. Scholar
  53. 53.
    Gormeli G, Karakaplan M, Gormeli CA, Sar kaya B, Elmal N, Ersoy Y. Clinical effects of platelet-rich plasma and hyaluronic acid as an additional therapy for talar osteochondral lesions treated with microfracture surgery: a prospective randomized clinical trial. Foot Ankle Int. 2015;36(8):891–900. Scholar
  54. 54.
    Guney A, Akar M, Karaman I, Oner M, Guney B. Clinical outcomes of platelet rich plasma (PRP) as an adjunct to microfracture surgery in osteochondral lesions of the talus. Knee Surg Sport Traumatol Arthrosc. 2015;23(8):2384–9. Scholar
  55. 55.
    Jazzo SF, Scribner D, Shay S, Kim K-M. Patient-reported outcomes following platelet-rich plasma injections in treating osteochondral lesions of the talus: a critically appraised topic. J Sport Rehabil. 2016;10(1):1–23. Scholar
  56. 56.
    Castillo TN, Pouliot MA, Kim HJ, Dragoo JL. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med. 2011;39(2):266–71. Scholar
  57. 57.
    Braun HJ, Kim HJ, Chu CR, Dragoo JL. The effect of platelet-rich plasma formulations and blood products on human synoviocytes: implications for intra-articular injury and therapy. Am J Sports Med. 2014;42(5):1204–10. Scholar
  58. 58.
    Gigante A, Cecconi S, Calcagno S, Busilacchi A, Enea D. Arthroscopic knee cartilage repair with covered microfracture and bone marrow concentrate. Arthrosc Tech. 2012;1(2):e175–80. Scholar
  59. 59.
    Kasten P. Instant stem cell therapy: characterization and concentration of human mesenchymal stem cells in vitro. Europe. 2008;16:47–55. Scholar
  60. 60.
    Scarpone M, Chambers A, Kuebler D. Bone marrow aspirates obtained using a novel needle system contain high numbers of mesenchymal stem cells. Int Orthop. 2018.; In PressGoogle Scholar
  61. 61.
    Chahla J, Dean CS, Moatshe G, Pascual-Garrido C, Serra Cruz R, LaPrade RF. Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: a systematic review of outcomes. Orthop J Sport Med. 2016;4(1):2325967115625481. Scholar
  62. 62.
    Huh SW, Shetty AA, Ahmed S, Lee DH, Kim SJ. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC). J Clin Orthop Trauma. 2016;7(3):153–6. Scholar
  63. 63.
    Fukumoto T, Sperling JW, Sanyal A, et al. Combined effects of insulin-like growth factor-1 and transforming growth factor-beta1 on periosteal mesenchymal cells during chondrogenesis in vitro. Osteoarthr Cartil. 2003;11(1):55–64. Scholar
  64. 64.
    Kuo AC, Rodrigo JJ, Reddi AH, Curtiss S, Grotkopp E, Chiu M. Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair. Osteoarthr Cartil. 2006;14(11):1126–35. Scholar
  65. 65.
    Fortier LA, Potter HG, Rickey EJ, et al. Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am. 2010;92(10):1927–37. Scholar
  66. 66.
    Saw KY, Hussin P, Loke SC, et al. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: an experimental study in a goat model. Arthrosc – J Arthrosc Relat Surg. 2009;25(12):1391–400. Scholar
  67. 67.
    De Girolamo L, Bertolini G, Cervellin M, Sozzi G, Volpi P. Treatment of chondral defects of the knee with one step matrix-assisted technique enhanced by autologous concentrated bone marrow: in vitro characterisation of mesenchymal stem cells from iliac crest and subchondral bone. Injury. 2010;41(11):1172–7. Scholar
  68. 68.
    Gobbi A, Whyte GP. One-stage cartilage repair using a hyaluronic acid-based scaffold with activated bone marrow-derived mesenchymal stem cells compared with microfracture: five-year follow-up. Am J Sports Med. 2016;44(11):2846–54. Scholar
  69. 69.
    Hannon CP, Ross KA, Murawski CD, et al. Arthroscopic bone marrow stimulation and concentrated bone marrow aspirate for osteochondral lesions of the talus: a case-control study of functional and magnetic resonance observation of cartilage repair tissue outcomes. Arthroscopy. 2016;32(2):339–47. Scholar
  70. 70.
    Kasir R, Vernekar VN, Laurencin CT. Regenerative engineering of cartilage using adipose-derived stem cells. Regen Eng Transl Med. 2015;1(1–4):42–9. Scholar
  71. 71.
    Wu L, Cai X, Zhang S, Karperien M, Lin Y. Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine. J Cell Physiol. 2013;228(5):938–44. Scholar
  72. 72.
    Huang S, Fu R, Shyu W. Adipose-derived stem cells: isolation, characterization, and differentiation potential. Cell Transplant. 2013;22:701–9. Scholar
  73. 73.
    Lai JH, Rogan H, Kajiyama G, et al. Interaction between osteoarthritic chondrocytes and adipose-derived stem cells is dependent on cell distribution in three-dimension and transforming growth factor-β3 induction. Tissue Eng Part A. 2015;21(5–6):992–1002. Scholar
  74. 74.
    Dragoo JL, Carlson G, McCormick F, et al. Healing full-thickness cartilage defects using adipose-derived stem cells. Tissue Eng. 2007;13(7):1615–21. Scholar
  75. 75.
    Nathan S, Das De S, Thambyah A, Fen C, Goh J, Lee EH. Cell-based therapy in the repair of osteochondral defects: a novel use for adipose tissue. Tissue Eng. 2003;9(4):733–44. Scholar
  76. 76.
    Dragoo JL, Chang W. Arthroscopic harvest of adipose-derived mesenchymal stem cells from the infrapatellar fat pad. Am J Sports Med. 2017:36354651771945.
  77. 77.
    Kim YS, Koh YG. Injection of mesenchymal stem cells as a supplementary strategy of marrow stimulation improves cartilage regeneration after lateral sliding calcaneal osteotomy for varus ankle osteoarthritis: clinical and second-look arthroscopic results. Arthrosc – J Arthrosc Relat Surg. 2016;32(5):878–89. Scholar
  78. 78.
    Kim YS, Lee HJ, Choi YJ, Kim YI, Koh YG. Does an injection of a stromal vascular fraction containing adipose-derived mesenchymal stem cells influence the outcomes of marrow stimulation in osteochondral lesions of the talus? A clinical and magnetic resonance imaging study. Am J Sports Med. 2014;42(10):2424–34. Scholar
  79. 79.
    Koh Y-G, Kwon O-R, Kim Y-S, Choi Y-J, Tak D-H. Adipose-derived mesenchymal stem cells with microfracture versus microfracture alone: 2-year follow-up of a prospective randomized trial. Arthrosc J Arthrosc Relat Surg. 2016;32(1):97–109. Scholar
  80. 80.
    Benthien JP, Behrens P. Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling: a technical note. Int Orthop. 2013;37(11):2139–45. Scholar
  81. 81.
    Zedde P, Cudoni S, Giachetti G, et al. Subchondral bone remodeling: comparing nanofracture with microfracture. An ovine in vivo study. Joints. 2016;4(2):87–93. Scholar
  82. 82.
    Tahta M, Akkaya M, Gursoy S, Isik C, Bozkurt M. Arthroscopic treatment of osteochondral lesions of the talus: nanofracture versus hyaluronic acid-based cell-free scaffold with concentration of autologous bone marrow aspirate. J Orthop Surg. 2017.
  83. 83.
    Hirahara AM, Mueller KW. BioCartilage: a new biomaterial to treat chondral lesions. Sports Med Arthrosc. 2015;23(3):143–8. Scholar
  84. 84.
    Fortier LA, Chapman HS, Pownder SL, et al. BioCartilage improves cartilage repair compared with microfracture alone in an equine model of full-thickness cartilage loss. Am J Sports Med. 2016;44(9):2366–74. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Michael L. Redondo
    • 1
  • Brian R. Waterman
    • 1
  • Jack M. Bert
    • 2
  • Brian J. Cole
    • 1
    Email author
  1. 1.Department of Orthopedic SurgeryCartilage Restoration Center at Rush University Medical Center Midwest Orthopedic at RushChicagoUSA
  2. 2.Minnesota Bone & Joint Specialists, LtdSt. PaulUSA

Personalised recommendations