Advertisement

Enhanced microfracture using acellular scaffolds improves results after treatment of symptomatic focal grade III/IV knee cartilage lesions but current clinical evidence does not allow unequivocal recommendation

  • Cristiana Branco da CunhaEmail author
  • Renato Andrade
  • Tiago Rafael Veloso
  • David A. Learmonth
  • João Espregueira-Mendes
  • Rui A. Sousa
KNEE
  • 29 Downloads

Abstract

Purpose

To systematically analyse post-operative outcomes following enhanced microfracture procedures in focal cartilage injuries of the knee.

Methods

Database searches were conducted in PubMed, EMBASE and Cochrane Library databases up to 30 November 2018, for clinical studies in humans that assessed surgical outcomes of enhanced microfracture procedures in focal cartilage injuries of the knee. The clinical, functional and imaging outcomes were assessed and summarized. The MINORS scale was used to assess the methodological quality of the studies included.

Results

Ten studies were included comprising a total of 331 patients (mean age of 37.0 ± 5.5 years, body mass 25.2 ± 1.7 kg m2, 56% male and 42% left knee), 278 femoral condyle chondral defects (147 medial, 35 lateral and 78 undefined) and 43 chondral defects distributed by the tibial plateau, patella and femoral trochlea. The chondral defects were mostly Outerbridge grade III or IV and the mean defect size was 3.2 ± 0.6 cm2. Studies consistently demonstrated significant improvement in the patient-reported outcome measures from baseline to final follow-up. Overall, imaging outcomes showed inconsistent results. Treatment-related adverse events were poorly reported.

Conclusion

Enhanced microfracture techniques significantly result in improved patient-reported outcome measures over the MCID, but provide inconsistent imaging results. Current clinical evidence does not allow for unequivocal recommendation of enhanced microfracture to treat symptomatic focal grade III/IV knee cartilage lesions.

Level of evidence

IV.

Keywords

Enhanced microfracture Microfracture Cartilage Chondral Osteochondral 

Abbreviations

MFX

Microfracture

MCID

Minimal clinically important difference

AMIC

The autologous matrix-induced chondrogenesis

CS

Chondroitin sulphate

MRI

Magnetic resonance imaging

MOCART

Magnetic Resonance Observation of Cartilage Repair Tissue

IKDC

International Knee Documentation Committee Subjective Knee Form

WOMAC

Western Ontario and McMaster Universities Arthritis Index

KOOS

Knee Injury and Osteoarthritis Outcome Score

VAS

Visual Analogue Scale

Notes

Authors’ contributions

CBC, TRV and RA designed and implemented the systematic review protocol, CBC, TRV and RA collected, analyzed and interpreted the data collected, CBC, TRV and RA critically reviewed the scientific content of the manuscript, CBC, RA, JEM and RAS drafted the manuscript, and all authors (CBC, RA, TRV, DAL, JEM and RAS) have read, reviewed and given final approval for the version to be published.

Funding

The authors declare that there was no funding for this study.

Compliance with ethical standards

Conflict of interest

JEM and RAS are shareholders, and CBC, TRV, DAL and RAS are current employees of Stemmatters, Biotecnologia e Medicina Regenerativa SA. Stemmatters is currently developing a proprietary medical device to be used in the context of enhanced microfracture surgical treatment. Stemmatters is actively pursuing patents related to the content of the manuscript. This manuscript was not influenced by personal or financial relationship with Stemmatters or any other third party.

Ethical approval

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

Supplementary material

167_2019_5832_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 kb)
167_2019_5832_MOESM2_ESM.docx (18 kb)
Supplementary material 2 (DOCX 17 kb)

References

  1. 1.
    Anders S (2013) A randomized, controlled trial comparing autologous matrix-induced chondrogenesis (AMIC®) to microfracture: analysis of 1- and 2-year follow-up data of 2 centers. Open Orthop J 3:133–143CrossRefGoogle Scholar
  2. 2.
    Arshi A, Fabricant PD, Go DE, Williams RJ, McAllister DR, Jones KJ (2018) Can biologic augmentation improve clinical outcomes following microfracture for symptomatic cartilage defects of the knee? A systematic review. Cartilage 9:146–155PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Benthien JP, Behrens P (2010) Autologous matrix-induced chondrogenesis (AMIC): combining microfracturing and a collagen I/III Matrix for articular cartilage resurfacing. Cartilage 1:65–68PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Bertho P, Pauvert A, Pouderoux T, Robert H (2018) Treatment of large deep osteochondritis lesions of the knee by autologous matrix-induced chondrogenesis (AMIC): preliminary results in 13 patients. Orthop Traumatol Surg Res 104:695–700PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Brown WE, Potter HG, Marx RG, Wickiewicz TL, Warren RF (2004) Magnetic resonance imaging appearance of cartilage repair in the knee. Clin Orthop Relat Res 422:214–223CrossRefGoogle Scholar
  6. 6.
    Chevrier A, Hoemann CD, Sun J, Buschmann MD (2007) Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularization and subchondral bone remodeling in drilled cartilage defects. Osteoarthr Cartil 15:316–327PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Chuah YJ, Peck Y, Lau JEJ, Hee HT, Wang D-A (2017) Hydrogel based cartilaginous tissue regeneration: recent insights and technologies. Biomater Sci 5:613–631PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Chung JY, Lee DH, Kim TH, Kwack KS, Yoon KH, Min BH (2014) Cartilage extra-cellular matrix biomembrane for the enhancement of microfractured defects. Knee Surg Sport Traumatol Arthrosc 22:1249–1259CrossRefGoogle Scholar
  9. 9.
    D’Antimo C, Biggi F, Borean A, Di Fabio S, Pirola I (2017) Combining a novel leucocyte-platelet-concentrated membrane and an injectable collagen scaffold in a single-step AMIC procedure to treat chondral lesions of the knee: a preliminary retrospective study. Eur J Orthop Surg Traumatol 27:673–681PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Devitt BM, Bell SW, Webster KE, Feller JA, Whitehead TS (2017) Surgical treatments of cartilage defects of the knee: systematic review of randomised controlled trials. Knee 24:508–517PubMedCrossRefGoogle Scholar
  11. 11.
    Gao L, Orth P, Cucchiarini M, Madry H (2019) Autologous matrix-induced chondrogenesis: a systematic review of the clinical evidence. Am J Sports Med 47:222–231PubMedCrossRefGoogle Scholar
  12. 12.
    Gille J, Behrens P, Volpi P, de Girolamo L, Reiss E, Zoch W, Anders S (2013) Outcome of Autologous Matrix Induced Chondrogenesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch Orthop Trauma Surg 133:87–93PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Goyal D, Keyhani S, Lee EH, Hui JHP (2013) Evidence-based status of microfracture technique: a systematic review of level I and II studies. Arthroscopy 29:1579–1588PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Hancock KJ, Westermann RR, Shamrock AG, Duchman KR, Wolf BR, Amendola A (2019) Trends in knee articular cartilage treatments: an american board of orthopaedic surgery database study. J Knee Surg 32:85–90PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Heijink A, Gomoll AH, Madry H, Drobnic M, Filardo G, Espregueira-Mendes J, Van Dijk CN (2012) Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 20:423–435PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Hoemann CD, Hurtig M, Rossomacha E, Sun J, Chevrier A, Shive MS, Buschmann MD (2005) Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. J Bone Joint Surg Am 87:2671–2686PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Hoemann CD, Sun J, McKee MD, Chevrier A, Rossomacha E, Rivard G-E, Hurtig M, Buschmann MD (2007) Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects. Osteoarthritis Cartilage 15:78–89PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Hoemann CD, Tran-Khanh N, Chevrier A, Chen G, Lascau-Coman V, Mathieu C, Changoor A, Yaroshinsky A, McCormack RG, Stanish WD, Buschmann MD (2015) Chondroinduction Is the Main Cartilage Repair Response to Microfracture and Microfracture With BST-CarGel: results as Shown by ICRS-II Histological Scoring and a Novel Zonal Collagen Type Scoring Method of Human Clinical Biopsy Specimens. Am J Sports Med 43:2469–2480PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Ioannidis JPA (2005) Why most published research findings are false. PLoS Med 2:e124PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Irrgang J (2012) Summary of clinical outcome measures for sports-related knee injuries. AOSSM Outcomes Task Force. http://www.privatehomepage.com. Accessed 03 Oct 2019
  21. 21.
    Jones KJ, Kelley BV, Arshi A, McAllister DR, Fabricant PD (2019) Comparative effectiveness of cartilage repair with respect to the minimal clinically important difference. Am J Sports Med.  https://doi.org/10.1177/0363546518824552 CrossRefPubMedGoogle Scholar
  22. 22.
    Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O (2007) A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am 89:2105–2112PubMedCrossRefGoogle Scholar
  23. 23.
    Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O (2004) Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 86:455–464PubMedCrossRefGoogle Scholar
  24. 24.
    Kusano T, Jakob RP, Gautier E, Magnussen RA, Hoogewoud H, Jacobi M (2012) Treatment of isolated chondral and osteochondral defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Knee Surg Sport Traumatol Arthrosc 20:2109–2115CrossRefGoogle Scholar
  25. 25.
    Lee YHD, Suzer F, Thermann H (2014) Autologous matrix-induced chondrogenesis in the knee: a review. Cartilage 5:145–153PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA (2014) Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 11:21–34PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Methot S, Changoor A, Tran-Khanh N, Hoemann CD, Stanish WD, Restrepo A, Shive MS, Buschmann MD (2016) Osteochondral biopsy analysis demonstrates that BST-CarGel treatment improves structural and cellular characteristics of cartilage repair tissue compared with microfracture. Cartilage 7:16–28PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR (2009) Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 37:2053–2063PubMedCrossRefGoogle Scholar
  29. 29.
    Mithoefer K, Venugopal V, Manaqibwala M (2016) Incidence, degree, and clinical effect of subchondral bone overgrowth after microfracture in the knee. Am J Sports Med 44:2057–2063PubMedCrossRefGoogle Scholar
  30. 30.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(264–9):W64Google Scholar
  31. 31.
    Montgomery SR, Foster BD, Ngo SS, Terrell RD, Wang JC, Petrigliano FA, McAllister DR (2014) Trends in the surgical treatment of articular cartilage defects of the knee in the United States. Knee Surg Sports Traumatol Arthrosc 22:2070–2075PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Moyad TF (2011) Cartilage injuries in the adult knee: evaluation and management. Cartilage 2:226–236PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Orth P, Gao L, Madry H (2019) Microfracture for cartilage repair in the knee: a systematic review of the contemporary literature. Knee Surg Sports Traumatol Arthrosc.  https://doi.org/10.1007/s00167-019-05359-9 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Pascarella A, Ciatti R, Pascarella F, Latte C, Di Salvatore MG, Liguori L, Iannella G (2010) Treatment of articular cartilage lesions of the knee joint using a modified AMIC technique. Knee Surg Sport Traumatol Arthrosc 18:509–513CrossRefGoogle Scholar
  35. 35.
    Patrascu JM, Freymann U, Kaps C, Poenaru DV (2010) Repair of a post-traumatic cartilage defect with a cell-free polymer-based cartilage implant: a follow-up at two years by MRI and histological review. J Bone Joint Surg Br 92:1160–1163PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Pipino G, Risitano S, Alviano F, Wu EJ, Bonsi L, Vaccarisi DC, Indelli PF (2019) Microfractures and hydrogel scaffolds in the treatment of osteochondral knee defects: a clinical and histological evaluation. J Clin Orthop Trauma 10:67–75PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Roos EMLL (2003) The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Heal Qual Life Outcomes 1:64CrossRefGoogle Scholar
  38. 38.
    Saltzman BM, Redondo ML, Beer A, Cotter EJ, Frank RM, Yanke AB, Cole BJ (2018) Wide variation in methodology in Level I and II studies on cartilage repair: a systematic review of available clinical trials comparing patient demographics, treatment means, and outcomes reporting. Cartilage.  https://doi.org/10.1177/1947603518809398 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Schiavone A, Chiara P, Regno D, Mazzitelli G, Apolito RD, Corona K, Vasso M (2017) Good clinical results with autologous matrix-induced chondrogenesis (Amic) technique in large knee chondral defects. Knee Surg Sport Traumatol Arthrosc 26:1130–1136Google Scholar
  40. 40.
    Schneider U (2016) Controlled, randomized multicenter study to compare compatibility and safety of ChondroFiller liquid (cell free 2-component collagen gel) with microfracturing of patients with focal cartilage defects of the knee joint. Video J Orthop Surg 1:1–8Google Scholar
  41. 41.
    Shaikh N, Seah MKT, Khan WS (2017) Systematic review on the use of autologous matrix-induced chondrogenesis for the repair of articular cartilage defects in patients. World J Orthop 8:588–601PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Sharma B, Fermanian S, Gibson M, Unterman S, Herzka DA, Cascio B, Coburn J, Hui AY, Marcus N, Gold GE, Elisseeff JH (2013) Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci Transl Med 5:1676CrossRefGoogle Scholar
  43. 43.
    Shimozono Y, Yasui Y, Ross AW, Miyamoto W, Kennedy JG (2017) Scaffolds based therapy for osteochondral lesions of the talus: a systematic review. World J Orthop 8:798–808PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Shive MS, Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Méthot S, Vehik K, Restrepo A (2015) BST-CarGel® treatment maintains cartilage repair superiority over microfracture at 5 years in a multicenter randomized controlled trial. Cartilage 6:62–72PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Siclari A, Mascaro G, Gentili C, Cancedda R, Boux E (2012) A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year. Clin Orthop Relat Res 470:910–919PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Siclari A, Mascaro G, Gentili C, Kaps C, Cancedda R, Boux E (2014) Cartilage repair in the knee with subchondral drilling augmented with a platelet-rich plasma-immersed polymer-based implant. Knee Surg Sports Traumatol Arthrosc 22:1225–1234PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Siclari A, Mascaro G, Kaps C, Boux E (2014) A 5-year follow-up after cartilage repair in the knee using a platelet-rich plasma-immersed polymer-based implant. Open Orthop J 8:346–354PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J (2003) Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg 73:712–716PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Sofu H, Camurcu Y, Ucpunar H, Ozcan S, Yurten H, Sahin V (2019) Clinical and radiographic outcomes of chitosan-glycerol phosphate/blood implant are similar with hyaluronic acid-based cell-free scaffold in the treatment of focal osteochondral lesions of the knee joint. Knee Surg Sports Traumatol Arthrosc 27:773–781PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Solheim E, Hegna J, Inderhaug E (2017) Long-term clinical follow-up of microfracture versus mosaicplasty in articular cartilage defects of medial femoral condyle. Knee 24:1402–1407PubMedCrossRefGoogle Scholar
  51. 51.
    Solheim E, Hegna J, Inderhaug E (2018) Long-term survival after microfracture and mosaicplasty for knee articular cartilage repair: a comparative study between two treatments cohorts. Cartilage.  https://doi.org/10.1177/1947603518783482 CrossRefPubMedGoogle Scholar
  52. 52.
    Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Restrepo A, Shive MS (2013) Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. J Bone Joint Surg Am 95:1640–1650PubMedCrossRefGoogle Scholar
  53. 53.
    Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG (2003) Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19:477–484PubMedCrossRefGoogle Scholar
  54. 54.
    Steinwachs M, Cavalcanti N, Mauuva Venkatesh Reddy S, Werner C, Tschopp D, Choudur HN (2019) Arthroscopic and open treatment of cartilage lesions with BST-CARGEL scaffold and microfracture: a cohort study of consecutive patients. Knee 26:174–184PubMedCrossRefGoogle Scholar
  55. 55.
    Wolf MT, Zhang H, Sharma B, Marcus NA, Pietzner U, Fickert S, Lueth A, Albers GHR, Elisseeff JH (2018) Two-year follow-Up and remodeling kinetics of ChonDux hydrogel for full-thickness cartilage defect repair in the knee. Cartilage.  https://doi.org/10.1177/1947603518800547 CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2020

Authors and Affiliations

  1. 1.Stemmatters, Biotecnologia e Medicina Regenerativa SABarco, GuimarãesPortugal
  2. 2.Clínica do Dragão, Espregueira-Mendes Sports Centre-FIFA Medical Centre of ExcellencePortoPortugal
  3. 3.Dom Henrique Research CentrePortoPortugal
  4. 4.Faculty of SportsUniversity of PortoPortoPortugal
  5. 5.ICVS/3B’s-PT Government Associate LaboratoryBraga/GuimarãesPortugal
  6. 6.Life and Health Sciences Research Institute (ICVS), School of MedicineUniversity of MinhoBragaPortugal

Personalised recommendations