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J Knee Surg 2016; 29(05): 379-386
DOI: 10.1055/s-0036-1584194
Special Focus Section
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Use of Biologic Agents in Athletes with Knee Injuries

Michaela Kopka
1   Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
,
James P. Bradley
1   Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
› Author Affiliations
Further Information

Publication History

14 December 2015

28 March 2016

Publication Date:
20 May 2016 (online)

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Erratum: The Use of Biologic Agents in Athletes with Knee InjuriesJ Knee Surg 2016; 29(05): e4-e4
DOI: 10.1055/s-0037-1599135

Abstract

Biologic agents are gaining popularity in the management of bony and soft tissue conditions about the knee. They are becoming the mainstay of nonoperative therapy in the high-demand athletic population. The most well-studied agents include platelet-rich plasma (PRP) and stem cells—both of which have shown promise in the treatment of various conditions. Animal and clinical studies have demonstrated improved outcomes following PRP treatment in early osteoarthritis of the knee, as well as in chronic patellar tendinopathy. Early clinical evidence also lends support for PRP in the augmentation of anterior cruciate ligament (ACL) reconstruction. Research investigating the role of biologic agents in collateral ligament and meniscal injuries is ongoing. Studies assessing the utility of stem cells have shown encouraging results in the setting of osteoarthritis. Unfortunately, strict regulations by the FDA continue to restrict their application in clinical practice. A major limitation in the interpretation of current data is the significant variability in the harvesting and preparation of both PRP and stem cells. As the volume and quality of evidence continue to grow, biologic agents are poised to become an integral component of comprehensive patient care throughout all orthopedic specialties.

Keywords

biologic agents - platelet-rich plasma - stem cells - athletes
 

  • References

  • 1 Liddle AD, Rodríguez-Merchán EC. Platelet-rich plasma in the treatment of patellar tendinopathy: a systematic review. Am J Sports Med 2015; 43 (10) 2583-2590
    CrossrefPubMedSearch in Google Scholar
  • 2 Charousset C, Zaoui A, Bellaiche L, Bouyer B. Are multiple platelet-rich plasma injections useful for treatment of chronic patellar tendinopathy in athletes? A prospective study. Am J Sports Med 2014; 42 (4) 906-911
    CrossrefPubMedSearch in Google Scholar
  • 3 Vangsness Jr CTJ, Farr II J, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am 2014; 96 (2) 90-98
    CrossrefPubMedSearch in Google Scholar
  • 4 Dragoo JL, Wasterlain AS, Braun HJ, Nead KT. Platelet-rich plasma as a treatment for patellar tendinopathy: a double-blind, randomized controlled trial. Am J Sports Med 2014; 42 (3) 610-618
    CrossrefPubMedSearch in Google Scholar
  • 5 Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy 2016; 32 (3) 495-505
    CrossrefPubMedSearch in Google Scholar
  • 6 Anz AW, Hackel JG, Nilssen EC, Andrews JR. Application of biologics in the treatment of the rotator cuff, meniscus, cartilage, and osteoarthritis. J Am Acad Orthop Surg 2014; 22 (2) 68-79
    CrossrefPubMedSearch in Google Scholar
  • 7 Williams PN, Moran G, Bradley JP, S. ElAttrache N, Dines JS. Platelet-rich plasma and other cellular strategies in orthopedic surgery. Curr Rev Musculoskelet Med 2015; 8 (1) 32-39
    CrossrefPubMedSearch in Google Scholar
  • 8 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) 266-271
    CrossrefPubMedSearch in Google Scholar
  • 9 Choi BH, Zhu SJ, Kim BY, Huh JY, Lee SH, Jung JH. Effect of platelet-rich plasma (PRP) concentration on the viability and proliferation of alveolar bone cells: an in vitro study. Int J Oral Maxillofac Surg 2005; 34 (4) 420-424
    CrossrefPubMedSearch in Google Scholar
  • 10 Graziani F, Cei S, Ducci F, Giuca MR, Donos N, Gabriele M. In vitro effects of different concentration of PRP on primary bone and gingival cell lines. Preliminary results. Minerva Stomatol 2005; 54 (1–2) 15-22
    PubMedSearch in Google Scholar
  • 11 Dragoo JL, Braun HJ, Durham JL , et al. Comparison of the acute inflammatory response of two commercial platelet-rich plasma systems in healthy rabbit tendons. Am J Sports Med 2012; 40 (6) 1274-1281
    CrossrefPubMedSearch in Google Scholar
  • 12 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) 1204-1210
    CrossrefPubMedSearch in Google Scholar
  • 13 DeLong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: the PAW classification system. Arthroscopy 2012; 28 (7) 998-1009
    CrossrefPubMedSearch in Google Scholar
  • 14 Caplan AI, Correa D. PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs. J Orthop Res 2011; 29 (12) 1795-1803
    CrossrefPubMedSearch in Google Scholar
  • 15 Cesselli D, Beltrami AP, Rigo S , et al. Multipotent progenitor cells are present in human peripheral blood. Circ Res 2009; 104 (10) 1225-1234
    CrossrefPubMedSearch in Google Scholar
  • 16 US Department of Health and Human Services Web site. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/ucm427795.htm . Updated February 2015
    PubMed
  • 17 US Department of Health and Human Services website. http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-bio-gen/documents/document/ucm469751.pdf . Updated October 2015.
    PubMed
  • 18 Ardern CL, Webster KE, Taylor NF, Feller JA. Return to sport following anterior cruciate ligament reconstruction surgery: a systematic review and meta-analysis of the state of play. Br J Sports Med 2011; 45 (7) 596-606
    CrossrefPubMedSearch in Google Scholar
  • 19 Kamath GV, Murphy T, Creighton RA, Viradia N, Taft TN, Spang JT. Anterior cruciate ligament injury, return to play, and reinjury in the elite collegiate athlete: analysis of an NCAA Division I Cohort. Am J Sports Med 2014; 42 (7) 1638-1643
    CrossrefPubMedSearch in Google Scholar
  • 20 Orrego M, Larrain C, Rosales J , et al. Effects of platelet concentrate and a bone plug on the healing of hamstring tendons in a bone tunnel. Arthroscopy 2008; 24 (12) 1373-1380
    CrossrefPubMedSearch in Google Scholar
  • 21 Figueroa D, Melean P, Calvo R , et al. Magnetic resonance imaging evaluation of the integration and maturation of semitendinosus-gracilis graft in anterior cruciate ligament reconstruction using autologous platelet concentrate. Arthroscopy 2010; 26 (10) 1318-1325
    CrossrefPubMedSearch in Google Scholar
  • 22 Nin JR, Gasque GM, Azcárate AV, Beola JD, Gonzalez MH. Has platelet-rich plasma any role in anterior cruciate ligament allograft healing?. Arthroscopy 2009; 25 (11) 1206-1213
    CrossrefPubMedSearch in Google Scholar
  • 23 Vogrin M, Rupreht M, Dinevski D , et al. Effects of a platelet gel on early graft revascularization after anterior cruciate ligament reconstruction: a prospective, randomized, double-blind, clinical trial. Eur Surg Res 2010; 45 (2) 77-85
    CrossrefPubMedSearch in Google Scholar
  • 24 Figueroa D, Figueroa F, Calvo R, Vaisman A, Ahumada X, Arellano S. Platelet-rich plasma use in anterior cruciate ligament surgery: systematic review of the literature. Arthroscopy 2015; 31 (5) 981-988
    CrossrefPubMedSearch in Google Scholar
  • 25 Lui PP, Wong OT, Lee YW. Application of tendon-derived stem cell sheet for the promotion of graft healing in anterior cruciate ligament reconstruction. Am J Sports Med 2014; 42 (3) 681-689
    CrossrefPubMedSearch in Google Scholar
  • 26 Bedi A, Kelly NH, Baad M , et al. Dynamic contact mechanics of the medial meniscus as a function of radial tear, repair, and partial meniscectomy. J Bone Joint Surg Am 2010; 92 (6) 1398-1408
    CrossrefPubMedSearch in Google Scholar
  • 27 Bedi A, Kelly N, Baad M , et al. Dynamic contact mechanics of radial tears of the lateral meniscus: implications for treatment. Arthroscopy 2012; 28 (3) 372-381
    CrossrefPubMedSearch in Google Scholar
  • 28 McDermott I. Meniscal tears, repairs and replacement: their relevance to osteoarthritis of the knee. Br J Sports Med 2011; 45 (4) 292-297
    CrossrefPubMedSearch in Google Scholar
  • 29 Hutchinson ID, Moran CJ, Potter HGW, Warren RF, Rodeo SA. Restoration of the meniscus: form and function. Am J Sports Med 2014; 42 (4) 987-998
    CrossrefPubMedSearch in Google Scholar
  • 30 Makris EA, Hadidi P, Athanasiou KA. The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials 2011; 32 (30) 7411-7431
    CrossrefPubMedSearch in Google Scholar
  • 31 Ionescu LC, Lee GC, Huang KL, Mauck RL. Growth factor supplementation improves native and engineered meniscus repair in vitro. Acta Biomater 2012; 8 (10) 3687-3694
    CrossrefPubMedSearch in Google Scholar
  • 32 Ishida K, Kuroda R, Miwa M , et al. The regenerative effects of platelet-rich plasma on meniscal cells in vitro and its in vivo application with biodegradable gelatin hydrogel. Tissue Eng 2007; 13 (5) 1103-1112
    CrossrefPubMedSearch in Google Scholar
  • 33 Griffin JW, Hadeed MM, Werner BC, Diduch DR, Carson EW, Miller MD. Platelet-rich plasma in meniscal repair: does augmentation improve surgical outcomes?. Clin Orthop Relat Res 2015; 473 (5) 1665-1672
    CrossrefPubMedSearch in Google Scholar
  • 34 Pujol N, Salle De Chou E, Boisrenoult P, Beaufils P. Platelet-rich plasma for open meniscal repair in young patients: any benefit?. Knee Surg Sports Traumatol Arthrosc 2015; 23 (1) 51-58
    CrossrefPubMedSearch in Google Scholar
  • 35 Angele P, Johnstone B, Kujat R , et al. Stem cell based tissue engineering for meniscus repair. J Biomed Mater Res A 2008; 85 (2) 445-455
    PubMedSearch in Google Scholar
  • 36 Zellner J, Mueller M, Berner A , et al. Role of mesenchymal stem cells in tissue engineering of meniscus. J Biomed Mater Res A 2010; 94 (4) 1150-1161
    PubMedSearch in Google Scholar
  • 37 Kettunen JA, Kvist M, Alanen E, Kujala UM. Long-term prognosis for jumper's knee in male athletes. A prospective follow-up study. Am J Sports Med 2002; 30 (5) 689-692
    CrossrefPubMedSearch in Google Scholar
  • 38 Ferretti A, Conteduca F, Camerucci E, Morelli F. Patellar tendinosis: a follow-up study of surgical treatment. J Bone Joint Surg Am 2002; 84-A (12) 2179-2185
    PubMedSearch in Google Scholar
  • 39 Kaeding CC, Pedroza AD, Powers BC. Surgical treatment of chronic patellar tendinosis: a systematic review. Clin Orthop Relat Res 2007; 455 (455) 102-106
    CrossrefPubMedSearch in Google Scholar
  • 40 Vetrano M, Castorina A, Vulpiani MC, Baldini R, Pavan A, Ferretti A. Platelet-rich plasma versus focused shock waves in the treatment of jumper's knee in athletes. Am J Sports Med 2013; 41 (4) 795-803
    CrossrefPubMedSearch in Google Scholar
  • 41 Filardo G, Kon E, Della Villa S, Vincentelli F, Fornasari PMM, Marcacci M. Use of platelet-rich plasma for the treatment of refractory jumper's knee. Int Orthop 2010; 34 (6) 909-915
    CrossrefPubMedSearch in Google Scholar
  • 42 Kon E, Filardo G, Delcogliano M , et al. Platelet-rich plasma: new clinical application: a pilot study for treatment of jumper's knee. Injury 2009; 40 (6) 598-603
    CrossrefPubMedSearch in Google Scholar
  • 43 Pascual-Garrido C, Rolón A, Makino A. Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells: a 5-year-followup. Stem Cells Int 2012; 2012: 953510
    PubMedSearch in Google Scholar
  • 44 Yoshioka T, Kanamori A, Washio T , et al. The effects of plasma rich in growth factors (PRGF-Endoret) on healing of medial collateral ligament of the knee. Knee Surg Sports Traumatol Arthrosc 2013; 21 (8) 1763-1769
    CrossrefPubMedSearch in Google Scholar
  • 45 Eirale C, Mauri E, Hamilton B. Use of platelet rich plasma in an isolated complete medial collateral ligament lesion in a professional football (soccer) player: a case report. Asian J Sports Med 2013; 4 (2) 158-162
    PubMedSearch in Google Scholar
  • 46 Saether EE, Chamberlain CS, Leiferman EM , et al. Enhanced medial collateral ligament healing using mesenchymal stem cells: dosage effects on cellular response and cytokine profile. Stem Cell Rev 2014; 10 (1) 86-96
    CrossrefPubMedSearch in Google Scholar
  • 47 Smyth NA, Murawski CD, Fortier LA, Cole BJ, Kennedy JG. Platelet-rich plasma in the pathologic processes of cartilage: review of basic science evidence. Arthroscopy 2013; 29 (8) 1399-1409
    CrossrefPubMedSearch in Google Scholar
  • 48 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) 845-852
    CrossrefPubMedSearch in Google Scholar
  • 49 Kon E, Buda R, Filardo G , et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 2010; 18 (4) 472-479
    CrossrefPubMedSearch in Google Scholar
  • 50 Filardo G, Kon E, Buda R , et al. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2011; 19 (4) 528-535
    CrossrefPubMedSearch in Google Scholar
  • 51 Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med 2013; 41 (2) 356-364
    CrossrefPubMedSearch in Google Scholar
  • 52 Filardo G, Kon E, Di Martino A , et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord 2012; 13: 229
    CrossrefPubMedSearch in Google Scholar
  • 53 Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole BJ. Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis. Am J Sports Med 2016; 44 (3) 792-800
    CrossrefPubMedSearch in Google Scholar
  • 54 Wakitani S, Goto T, Pineda SJ , et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 1994; 76 (4) 579-592
    CrossrefPubMedSearch in Google Scholar
  • 55 Chang CH, Kuo TF, Lin FH , et al. Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model. J Orthop Res 2011; 29 (12) 1874-1880
    CrossrefPubMedSearch in Google Scholar
  • 56 McIlwraith CW, Frisbie DD, Rodkey WG , et al. Evaluation of intra-articular mesenchymal stem cells to augment healing of microfractured chondral defects. Arthroscopy 2011; 27 (11) 1552-1561
    CrossrefPubMedSearch in Google Scholar
  • 57 Koh YG, Choi YJ, Kwon OR, Kim YS. Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. Am J Sports Med 2014; 42 (7) 1628-1637
    CrossrefPubMedSearch in Google Scholar
  • 58 Jo CH, Lee YG, Shin WH , et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 2014; 32 (5) 1254-1266
    CrossrefPubMedSearch in Google Scholar
  • 59 Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 2010; 38 (6) 1110-1116
    CrossrefPubMedSearch in Google Scholar
  • 60 Saw KY, Anz A, Siew-Yoke Jee C , et al. Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy 2013; 29 (4) 684-694
    CrossrefPubMedSearch in Google Scholar
  • 61 Kim YS, Choi YJ, Koh YG. Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes. Am J Sports Med 2015; 43 (9) 2293-2301
    CrossrefPubMedSearch in Google Scholar
  • 62 Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med 2011; 39 (10) 2135-2140
    CrossrefPubMedSearch in Google Scholar