Basic science of anterior cruciate ligament injury and repair

A M Kiapour, M M Murray, A M Kiapour, M M Murray

Abstract

Injury to the anterior cruciate ligament (ACL) is one of the most devastating and frequent injuries of the knee. Surgical reconstruction is the current standard of care for treatment of ACL injuries in active patients. The widespread adoption of ACL reconstruction over primary repair was based on early perception of the limited healing capacity of the ACL. Although the majority of ACL reconstruction surgeries successfully restore gross joint stability, post-traumatic osteoarthritis is commonplace following these injuries, even with ACL reconstruction. The development of new techniques to limit the long-term clinical sequelae associated with ACL reconstruction has been the main focus of research over the past decades. The improved knowledge of healing, along with recent advances in tissue engineering and regenerative medicine, has resulted in the discovery of novel biologically augmented ACL-repair techniques that have satisfactory outcomes in preclinical studies. This instructional review provides a summary of the latest advances made in ACL repair. Cite this article: Bone Joint Res 2014;3:20-31.

Keywords: Anterior cruciate ligament; Injury; Repair.

Conflict of interest statement

ICMJE Conflict of Interest: None declared

Figures

Fig. 1
Fig. 1
Schematic showing the multi-planar loading mechanism of non-contact injury to the anterior cruciate ligament (Adapted and modified with permission from Levine et al).
Fig. 2
Fig. 2
Diagrams showing the differences in intrinsic healing response of the anterior cruciate ligament (ACL; top) and medial collateral ligament (MCL; bottom), highlighting the lack of provisional scaffold (blood clot) formation within the ACL wound site as the key mechanism for ACL healing failure (reproduced with permission from Murray and Fleming).
Fig. 3
Fig. 3
Representative photomicrographs of patellar ligament wounds (extra-articular, EA), untreated anterior cruciate ligament (ACL) wounds (intra-articular, IA) and treated ACL with collagen-platelet scaffold (IA Tx) at 21 days after injury (10x). Treated ACLs show similar distribution of protein presence as the patellar ligament. The untreated ACL wounds remain with almost no substratum (PDGF-A: platelet-derived growth factor; TGF-β: transforming growth factor; FGF: fibroblast growth factor) (adapted and modified with permission from Murray et al).
Fig. 4
Fig. 4
Schematic of bio-enhanced anterior cruciate ligament (ACL) repair method (adapted and modified with permission from Murray and Fleming).
Fig. 5
Fig. 5
Bar chart showing identical mechanical properties of bio-enhanced repaired anterior cruciate ligament (ACL) (Repair) compared with the surgically reconstructed samples (ACLR) (p > 0.6 for all comparisons), with significantly lower mechanical properties (*) within the untreated ACL rupture group (Tx) (reproduced with permission from Murray and Fleming).
Fig. 6
Fig. 6
Photographs showing the distal femoral cartilage at one year after a) an untreated anterior cruciate ligament (ACL) rupture, b) after conventional ACL reconstruction, and c) bio-enhanced ACL repair. Note the damage to the medial femoral condyle in the untreated and ACL-reconstructed knee (black arrows). No damage to the medial femoral condyle in the bio-enhanced ACL-repair knee (white arrow) was observed (adapted and modified with permission from Murray and Fleming ).

References

    1. Butler DL, Noyes FR, Grood ES. Ligamentous restraints to anterior-posterior drawer in the human knee: a biomechanical study. J Bone Joint Surg [Am] 1980;62-A:259–270
    1. Kiapour AM, Wordeman SC, Paterno MV, et al. Diagnostic value of knee arthrometry in the prediction of anterior cruciate ligament strain during landing. Am J Sports Med 2013;Epub.
    1. Levine JW, Kiapour AM, Quatman CE, et al. Clinically relevant injury patterns after an anterior cruciate ligament injury provide insight into injury mechanisms. Am J Sports Med 2013;41:385–395
    1. Quatman CE, Kiapour AM, Demetropoulos CK, et al. Preferential loading of the ACL compared with the MCL during landing: a novel in sim approach yields the multiplanar mechanism of dynamic valgus during ACL injuries. Am J Sports Med 2014;42:177–186
    1. Hewett TE, Di Stasi SL, Myer GD. Current concepts for injury prevention in athletes after anterior cruciate ligament reconstruction. Am J Sports Med 2013;41:216–224
    1. Chu CR, Beynnon BD, Buckwalter JA, et al. Closing the gap between bench and bedside research for early arthritis therapies (EARTH): report from the AOSSM/NIH U-13 Post-Joint Injury Osteoarthritis Conference II. Am J Sports Med 2011;39:1569–1578
    1. Lohmander LS, Ostenberg A, Englund M, Roos H. High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury. Arthritis Rheum 2004;50:3145–3152
    1. Nebelung W, Wuschech H. Thirty-five years of follow-up of anterior cruciate ligament-deficient knees in high-level athletes. Arthroscopy 2005;21:696–702
    1. von Porat A, Roos EM, Roos H. High prevalence of osteoarthritis 14 years after an anterior cruciate ligament tear in male soccer players: a study of radiographic and patient relevant outcomes. Ann Rheum Dis 2004;63:269–273
    1. Quatman CE, Kiapour A, Myer GD, et al. Cartilage pressure distributions provide a footprint to define female anterior cruciate ligament injury mechanisms. Am J Sports Med 2011;39:1706–1713
    1. Feagin JA Jr, Curl WW. Isolated tear of the anterior cruciate ligament: 5-year follow-up study. Am J Sports Med 1976;4:95–100
    1. Kaplan N, Wickiewicz TL, Warren RF. Primary surgical treatment of anterior cruciate ligament ruptures: a long-term follow-up study. Am J Sports Med 1990;18:354–358
    1. Marshall JL, Warren RF, Wickiewicz TL, Reider B. The anterior cruciate ligament: a technique of repair and reconstruction. Clin Orthop Relat Res 1979;143:97–106
    1. O’Donoghue DH, Frank GR, Jeter GL, et al. Repair and reconstruction of the anterior cruciate ligament in dogs: factors influencing long-term results. J Bone Joint Surg [Am] 1971;53-A:710–718
    1. Sandberg R, Balkfors B, Nilsson B, Westlin N. Operative versus non-operative treatment of recent injuries to the ligaments of the knee: a prospective randomized study. J Bone Joint Surg [Am] 1987;69-A:1120–1126
    1. Sherman MF, Bonamo JR. Primary repair of the anterior cruciate ligament. Clin Sports Med 1988;7:739–750
    1. Strand T, Molster A, Hordvik M, Krukhaug Y. Long-term follow-up after primary repair of the anterior cruciate ligament: clinical and radiological evaluation 15-23 years postoperatively. Arch Orthop Trauma Surg 2005;125:217–221
    1. Musahl V, Becker R, Fu FH, Karlsson J. New trends in ACL research. Knee Surg Sports Traumatol Arthrosc 2011;19(Suppl 1):S1–S3
    1. Murray JR, Lindh AM, Hogan NA, et al. Does anterior cruciate ligament reconstruction lead to degenerative disease?: thirteen-year results after bone-patellar tendon-bone autograft. Am. J Sports Med 2012;40:404–413
    1. Ardern CL, Webster KE, Taylor NF, Feller JA. Return to the preinjury level of competitive sport after anterior cruciate ligament reconstruction surgery: two-thirds of patients have not returned by 12 months after surgery. Am J Sports Med 2011;39:538–543
    1. Shelbourne KD, Gray T, Haro M. Incidence of subsequent injury to either knee within 5 years after anterior cruciate ligament reconstruction with patellar tendon autograft. Am J Sports Med 2009;37:246–251
    1. Spindler KP, Huston LJ, Wright RW, et al. The prognosis and predictors of sports function and activity at minimum 6 years after anterior cruciate ligament reconstruction: a population cohort study. Am J Sports Med 2011;39:348–359
    1. Kim S, Bosque J, Meehan JP, Jamali A, Marder R. Increase in outpatient knee arthroscopy in the United States: a comparison of National Surveys of Ambulatory Surgery, 1996 and 2006. J Bone Joint Surg [Am] 2011;93-A:994–1000
    1. Arendt E, Dick R. Knee injury patterns among men and women in collegiate basketball and soccer: NCAA data and review of literature. Am J Sports Med 1995;23:694–701
    1. Arendt EA, Agel J, Dick R. Anterior cruciate ligament injury patterns among collegiate men and women. J Athl Train 1999;34:86–92
    1. Gwinn DE, Wilckens JH, McDevitt ER, Ross G, Kao TC. The relative incidence of anterior cruciate ligament injury in men and women at the United States Naval Academy. Am J Sports Med 2000;28:98–102
    1. Lindenfeld TN, Schmitt DJ, Hendy MP, Mangine RE, Noyes FR. Incidence of injury in indoor soccer. Am J Sports Med 1994;22:364–371
    1. Messina DF, Farney WC, DeLee JC. The incidence of injury in Texas high school basketball. A prospective study among male and female athletes. Am J Sports Med 1999;27:294–299
    1. Myklebust G, Maehlum S, Holm I, Bahr R. A prospective cohort study of anterior cruciate ligament injuries in elite Norwegian team handball. Scand J Med Sci Sports 1998;8:149–153
    1. Renstrom P, Ljungqvist A, Arendt E, et al. Non-contact ACL injuries in female athletes: an International Olympic Committee current concepts statement. Br J Sports Med 2008;42:394–412
    1. Stevenson H, Webster J, Johnson R, Beynnon B. Gender differences in knee injury epidemiology among competitive alpine ski racers. Iowa Orthop J 1998;18:64–66
    1. Mather RC 3rd, Koenig L, Kocher MS, et al. Societal and economic impact of anterior cruciate ligament tears. J Bone Joint Surg [Am] 2013;95-A:1751–1759
    1. Griffin LY, Albohm MJ, Arendt EA, et al. Understanding and preventing noncontact anterior cruciate ligament injuries: a review of the Hunt Valley II meeting, January 2005. Am J Sports Med 2006;34:1512–1532
    1. Kiapour A, Kiapour AM, Kaul V, et al. Finite element model of the knee for investigation of injury mechanisms: development and validation. J Biomech Eng 2013;136:011002
    1. Kiapour AM, Kaul V, Kiapour A, et al. The effect of ligament modeling technique on knee joint kinematics: a finite element study. Appl Mathematics 2013;4:91–97
    1. Kiapour AM, Quatman CE, Goel VK, et al. Timing sequence of multi-planar knee kinematics revealed by physiologic cadaveric simulation of landing: Implications for ACL injury mechanism. Clin Biomech (Bristol, Avon) 2014:29:75–82
    1. Robson AW. VI: ruptured crucial ligaments and their repair by operation. Ann Surg 1903;37:716–718
    1. O’Donoghue DH, Rockwood CA Jr, Frank GR, Jack SC, Kenyon R. Repair of the anterior cruciate ligament in dogs. J Bone Joint Surg [Am] 1966;48-A:503–519
    1. Cabaud HE, Feagin JA, Rodkey WG. Acute anterior cruciate ligament injury and augmented repair: experimental studies. Am J Sports Med 1980;8:395–401
    1. Cabaud HE, Rodkey WG, Feagin JA. Experimental studies of acute anterior cruciate ligament injury and repair. Am J Sports Med 1979;7:18–22
    1. Hall M, Stevermer CA, Gillette JC. Gait analysis post anterior cruciate ligament reconstruction: knee osteoarthritis perspective. Gait Posture 2012;36:56–60
    1. Hoshino Y, Fu FH, Irrgang JJ, Tashman S. Can joint contact dynamics be restored by anterior cruciate ligament reconstruction? Clin Orthop Relat Res 2013;471:2924–2931
    1. Jansson KA, Harilainen A, Sandelin J, et al. Bone tunnel enlargement after anterior cruciate ligament reconstruction with the hamstring autograft and endobutton fixation technique. A clinical, radiographic and magnetic resonance imaging study with 2 years follow-up. Knee Surg Sports Traumatol Arthrosc 1999;7:290–295
    1. Kartus J, Magnusson L, Stener S, et al. Complications following arthroscopic anterior cruciate ligament reconstruction. A 2-5-year follow-up of 604 patients with special emphasis on anterior knee pain. Knee Surg Sports Traumatol Arthrosc 1999;7:2–8
    1. Shelbourne KD, Wilckens JH, Mollabashy A, DeCarlo M. Arthrofibrosis in acute anterior cruciate ligament reconstruction. The effect of timing of reconstruction and rehabilitation. Am J Sports Med 1991;19:332–336
    1. Beard DJ, Murray DW, Gill HS, et al. Reconstruction does not reduce tibial translation in the cruciate-deficient knee: an in vivo study. J Bone Joint Surg [Br] 2001;83-B:1098–1103
    1. Georgoulis AD, Papadonikolakis A, Papageorgiou CD, Mitsou A, Stergiou N. Three-dimensional tibiofemoral kinematics of the anterior cruciate ligament-deficient and reconstructed knee during walking. Am J Sports Med 2003;31:75–79
    1. Papannagari R, Gill TJ, Defrate LE, Moses JM, Petruska AJ, Li G. In vivo kinematics of the knee after anterior cruciate ligament reconstruction: a clinical and functional evaluation. Am J Sports Med 2006;34:2006–2012
    1. Tashman S, Kolowich P, Collon D, Anderson K, Anderst W. Dynamic function of the ACL-reconstructed knee during running. Clin Orthop Relat Res 2007;454:66–73
    1. Lohmander LS, Roos H. Knee ligament injury, surgery and osteoarthrosis: truth or consequences? Acta Orthop Scand 1994;65:605–609
    1. Muller B, Hofbauer M, Wongcharoenwatana J, Fu FH. Indications and contraindications for double-bundle ACL reconstruction. Int Orthop 2013;37:239–246
    1. Rabuck SJ, Middleton KK, Maeda S, et al. Individualized anatomic anterior cruciate ligament reconstruction. Arthrosc Tech 2012;1:23–29
    1. Kondo E, Yasuda K, Azuma H, Tanabe Y, Yagi T. Prospective clinical comparisons of anatomic double-bundle versus single-bundle anterior cruciate ligament reconstruction procedures in 328 consecutive patients. Am J Sports Med 2008;36:1675–1687
    1. Nagai T, Heebner NR, Sell TC, et al. Restoration of sagittal and transverse plane proprioception following anatomic double-bundle ACL reconstruction. Knee Surg Sports Traumatol Arthrosc 2013;21:2048–2056
    1. Seon JK, Gadikota HR, Wu JL, et al. Comparison of single- and double-bundle anterior cruciate ligament reconstructions in restoration of knee kinematics and anterior cruciate ligament forces. Am J Sports Med 2010;38:1359–1367
    1. Yagi M, Kuroda R, Nagamune K, Yoshiya S, Kurosaka M. Double-bundle ACL reconstruction can improve rotational stability. Clin Orthop Relat Res 2007;454:100–107
    1. Fu FH, Shen W, Starman JS, Okeke N, Irrgang JJ. Primary anatomic double-bundle anterior cruciate ligament reconstruction: a preliminary 2-year prospective study. Am J Sports Med 2008;36:1263–1274
    1. Gobbi A, Mahajan V, Karnatzikos G, Nakamura N. Single- versus double-bundle ACL reconstruction: is there any difference in stability and function at 3-year followup? Clin Orthop Relat Res 2012;470:824–834
    1. Hussein M, van Eck CF, Cretnik A, Dinevski D, Fu FH. Prospective randomized clinical evaluation of conventional single-bundle, anatomic single-bundle, and anatomic double-bundle anterior cruciate ligament reconstruction: 281 cases with 3- to 5-year follow-up. Am J Sports Med 2012;40:512–520
    1. Meredick RB, Vance KJ, Appleby D, Lubowitz JH. Outcome of single-bundle versus double-bundle reconstruction of the anterior cruciate ligament: a meta-analysis. Am J Sports Med 2008;36:1414–1421
    1. Song EK, Seon JK, Yim JH, et al. Progression of osteoarthritis after double- and single-bundle anterior cruciate ligament reconstruction. Am J Sports Med 2013;41:2340–2346
    1. Suomalainen P, Jarvela T, Paakkala A, Kannus P, Järvinen M. Double-bundle versus single-bundle anterior cruciate ligament reconstruction: a prospective randomized study with 5-year results. Am J Sports Med 2012;40:1511–1518
    1. Murray MM, Fleming BC. Biology of anterior cruciate ligament injury and repair: Kappa delta ann doner vaughn award paper 2013. J Orthop Res 2013;31:1501–1506
    1. Robayo LM, Moulin VJ, Tremblay P, et al. New ligament healing model based on tissue-engineered collagen scaffolds. Wound Repair Regen 2011;19:38–48
    1. Fisher MB, Liang R, Jung HJ, et al. Potential of healing a transected anterior cruciate ligament with genetically modified extracellular matrixbioscaffolds in a goat model. Knee Surg Sports Traumatol Arthrosc 2012;20:1357–1365
    1. Woo SL, Vogrin TM, Abramowitch SD. Healing and repair of ligament injuries in the knee. J Am Acad Orthop Surg 2000;8:364–372
    1. Xie J, Jiang J, Huang W, et al. TNF-alpha induced down-regulation of lysyl oxidase family in anterior cruciate ligament and medial collateral ligament fibroblasts. Knee 2013:Epub.
    1. Xie J, Jiang J, Zhang Y, et al. Up-regulation expressions of lysyl oxidase family in anterior cruciate ligament and medial collateral ligament fibroblasts induced by Transforming Growth Factor-Beta 1. Int Orthop 2012;36:207–213
    1. Xie J, Wang C, Huang DY, et al. TGF-beta1 induces the different expressions of lysyl oxidases and matrix metalloproteinases in anterior cruciate ligament and medial collateral ligament fibroblasts after mechanical injury. J Biomech 2013;46:890–898
    1. Xie J, Wang C, Yin L, et al. Interleukin-1 beta influences on lysyl oxidases and matrix metalloproteinases profile of injured anterior cruciate ligament and medial collateral ligament fibroblasts. Int Orthop 2013;37:495–505
    1. Zhang J, Yang L, Tang Z, et al. Expression of MMPs and TIMPs family in human ACL and MCL fibroblasts. Connect Tissue Res 2009;50:7–13
    1. Zhou D, Lee HS, Villarreal F, et al. Differential MMP-2 activity of ligament cells under mechanical stretch injury: an in vitro study on human ACL and MCL fibroblasts. J Orthop Res 2005;23:949–957
    1. Andrish J, Holmes R. Effects of synovial fluid on fibroblasts in tissue culture. Clin Orthop Relat Res 1979;279–283
    1. Barlow Y, Willoughby J. Pathophysiology of soft tissue repair. Br Med Bull 1992;48:698–711
    1. Murray MM, Spindler KP, Ballard P, et al. Enhanced histologic repair in a central wound in the anterior cruciate ligament with a collagen-platelet-rich plasma scaffold. J Orthop Res 2007;25:1007–1017
    1. Amiel D, Ishizue KK, Harwood FL, Kitabayashi L, Akeson WH. Injury of the anterior cruciate ligament: the role of collagenase in ligament degeneration. J Orthop Res 1989;7:486–493
    1. Beye JA, Hart DA, Bray RC, McDougall JJ, Salo PT. Injury-induced changes in mRNA levels differ widely between anterior cruciate ligament and medial collateral ligament. Am J Sports Med 2008;36:1337–1346
    1. Lee J, Harwood FL, Akeson WH, Amiel D. Growth factor expression in healing rabbit medial collateral and anterior cruciate ligaments. Iowa Orthop J 1998;18:19–25
    1. Menetrey J, Laumonier T, Garavaglia G, et al. alpha-Smooth muscle actin and TGF-beta receptor I expression in the healing rabbit medial collateral and anterior cruciate ligaments. Injury 2011;42:735–741
    1. Saris DB, Dhert WJ, Verbout AJ. Joint homeostasis: the discrepancy between old and fresh defects in cartilage repair. J Bone Joint Surg [Br] 2003;85-B:1067–1076
    1. Schreck PJ, Kitabayashi LR, Amiel D, Akeson WH, Woods VL Jr. Integrin display increases in the wounded rabbit medial collateral ligament but not the wounded anterior cruciate ligament. J Orthop Res 1995;13:174–183
    1. Sung KL, Kwan MK, Maldonado F, Akeson WH. Adhesion strength of human ligament fibroblasts. J Biomech Eng 1994;116:237–242
    1. Tang Z, Yang L, Wang Y, et al. Contributions of different intraarticular tissues to the acute phase elevation of synovial fluid MMP-2 following rat ACL rupture. J Orthop Res 2009;27:243–248
    1. Tang Z, Yang L, Xue R, et al. Differential expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in anterior cruciate ligament and medial collateral ligament fibroblasts after a mechanical injury: involvement of the p65 subunit of NF-kappaB. Wound Repair Regen 2009;17:709–716
    1. Gesink DS, Pacheco HO, Kuiper SD, et al. Immunohistochemical localization of beta 1-integrins in anterior cruciate and medial collateral ligaments of human and rabbit. J Orthop Res 1992;10:596–599
    1. Kobayashi K, Healey RM, Sah RL, et al. Novel method for the quantitative assessment of cell migration: a study on the motility of rabbit anterior cruciate (ACL) and medial collateral ligament (MCL) cells. Tissue Eng 2000;6:29–38
    1. Lo IK, Ou Y, Rattner JP, et al. The cellular networks of normal ovine medial collateral and anterior cruciate ligaments are not accurately recapitulated in scar tissue. J Anat 2002;200:283–296
    1. Lyon RM, Akeson WH, Amiel D, Kitabayashi LR, Woo SL. Ultrastructural differences between the cells of the medical collateral and the anterior cruciate ligaments. Clin Orthop Relat Res 1991;272:279–286
    1. McKean JM, Hsieh AH, Sung KL. Epidermal growth factor differentially affects integrin-mediated adhesion and proliferation of ACL and MCL fibroblasts. Biorheology 2004;41:139–152
    1. Nagineni CN, Amiel D, Green MH, Berchuck M, Akeson WH. Characterization of the intrinsic properties of the anterior cruciate and medial collateral ligament cells: an in vitro cell culture study. J Orthop Res 1992;10:465–475
    1. Wiig ME, Amiel D, Ivarsson M, et al. Type I procollagen gene expression in normal and early healing of the medial collateral and anterior cruciate ligaments in rabbits: an in situ hybridization study. J Orthop Res 1991;9:374–382
    1. Yoshida M, Fujii K. Differences in cellular properties and responses to growth factors between human ACL and MCL cells. J Orthop Sci 1999;4:293–298
    1. Bray RC, Leonard CA, Salo PT. Vascular physiology and long-term healing of partial ligament tears. J Orthop Res 2002;20:984–989
    1. Bray RC, Leonard CA, Salo PT. Correlation of healing capacity with vascular response in the anterior cruciate and medial collateral ligaments of the rabbit. J Orthop Res 2003;21:1118–1123
    1. Andersen HN, Amis AA. Review on tension in the natural and reconstructed anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc 1994;2:192–202
    1. Steadman J, Cameron M, Briggs K, Rodkey W. Healing-response treatment for ACL injuries. Orthop Tech Rev 2002;3:7
    1. Gobbi A, Bathan L, Boldrini L. Primary repair combined with bone marrow stimulation in acute anterior cruciate ligament lesions: results in a group of athletes. Am J Sports Med 2009;37:571–578
    1. Steadman JR, Cameron-Donaldson ML, Briggs KK, Rodkey WG. A minimally invasive technique (“healing response”) to treat proximal ACL injuries in skeletally immature athletes. J Knee Surg 2006;19:8–13
    1. Steadman JR, Matheny LM, Briggs KK, Rodkey WG, Carreira DS. Outcomes following healing response in older, active patients: a primary anterior cruciate ligament repair technique. J Knee Surg 2012;25:255–260
    1. Wasmaier J, Kubik-Huch R, Pfirrmann C, et al. Proximal anterior cruciate ligament tears: the healing response technique versus conservative treatment. J Knee Surg 2013;26:263–271
    1. Caplan AI. Mesenchymal stem cells. J Orthop Res 1991;9:641–650
    1. Caplan AI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 2007;213:341–347
    1. Caplan AI. Mesenchymal stem cells: the past, the present, the future. Cartilage 2010;1:6–9
    1. Awad HA, Boivin GP, Dressler MR, et al. Repair of patellar tendon injuries using a cell-collagen composite. J Orthop Res 2003;21:420–431
    1. Awad HA, Butler DL, Boivin GP, et al. Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng 1999;5:267–277
    1. 106 Bruder SP, Jaiswal N, Haynesworth SE. Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cell Biochem 1997;64:278–294
    1. Ge Z, Goh JC, Lee EH. The effects of bone marrow-derived mesenchymal stem cells and fascia wrap application to anterior cruciate ligament tissue engineering. Cell Transplant 2005;14:763–773
    1. Haynesworth SE, Goshima J, Goldberg VM, Caplan AI. Characterization of cells with osteogenic potential from human marrow. Bone 1992;13:81–88
    1. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 1998;238:265–272
    1. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–147
    1. Young RG, Butler DL, Weber W, et al. Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res 1998;16:406–413
    1. Kanaya A, Deie M, Adachi N, et al. Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model. Arthroscopy 2007;23:610–617
    1. Lim JK, Hui J, Li L, et al. Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction. Arthroscopy 2004;20:899–910
    1. Soon MY, Hassan A, Hui JH, Goh JC, Lee EH. An analysis of soft tissue allograft anterior cruciate ligament reconstruction in a rabbit model: a short-term study of the use of mesenchymal stem cells to enhance tendon osteointegration. Am J Sports Med 2007;35:962–971
    1. Oe K, Kushida T, Okamoto N, et al. New strategies for anterior cruciate ligament partial rupture using bone marrow transplantation in rats. Stem Cells Dev 2011;20:671–679
    1. Gerich TG, Kang R, Fu FH, Robbins PD, Evans CH. Gene transfer to the rabbit patellar tendon: potential for genetic enhancement of tendon and ligament healing. Gene Ther 1996;3:1089–1093
    1. Hildebrand KA, Frank CB, Hart DA. Gene intervention in ligament and tendon: current status, challenges, future directions. Gene Ther 2004;11:368–378
    1. Huard J, Li Y, Peng H, Fu FH. Gene therapy and tissue engineering for sports medicine. J Gene Med 2003;5:93–108
    1. Madry H, Kohn D, Cucchiarini M. Direct FGF-2 gene transfer via recombinant adeno-associated virus vectors stimulates cell proliferation, collagen production, and the repair of experimental lesions in the human ACL. Am J Sports Med 2013;41:194–202
    1. Menetrey J, Kasemkijwattana C, Day CS, et al. Direct-, fibroblast- and myoblast-mediated gene transfer to the anterior cruciate ligament. Tissue Eng 1999;5:435–442
    1. Nixon AJ, Watts AE, Schnabel LV. Cell- and gene-based approaches to tendon regeneration. J Shoulder Elbow Surg 2012;21:278–294
    1. Pascher A, Steinert AF, Palmer GD, et al. Enhanced repair of the anterior cruciate ligament by in situ gene transfer: evaluation in an in vitro model. Mol Ther 2004;10:327–336
    1. Steinert AF, Weber M, Kunz M, et al. In situ IGF-1 gene delivery to cells emerging from the injured anterior cruciate ligament. Biomaterials 2008;29:904–916
    1. Woo SL, Jia F, Zou L, Gabriel MT. Functional tissue engineering for ligament healing: potential of antisense gene therapy. Ann Biomed Eng 2004;32:342–351
    1. Attia E, Brown H, Henshaw R, George S, Hannafin JA. Patterns of gene expression in a rabbit partial anterior cruciate ligament transection model: the potential role of mechanical forces. Am J Sports Med 2010;38:348–356
    1. Wang Y, Tang Z, Xue R, et al. TGF-beta1 promoted MMP-2 mediated wound healing of anterior cruciate ligament fibroblasts through NF-kappaB. Connect Tissue Res 2011;52:218–225
    1. Hildebrand KA, Deie M, Allen CR, et al. Early expression of marker genes in the rabbit medial collateral and anterior cruciate ligaments: the use of different viral vectors and the effects of injury. J Orthop Res 1999;17:37–42
    1. Bonniaud P, Margetts PJ, Kolb M, et al. Adenoviral gene transfer of connective tissue growth factor in the lung induces transient fibrosis. Am J Respir Crit Care Med 2003;168:770–778
    1. Crystal RG. Transfer of genes to humans: early lessons and obstacles to success. Science 1995;270:404–410
    1. Amiel D, Nagineni CN, Choi SH, Lee J. Intrinsic properties of ACL and MCL cells and their responses to growth factors. Med Sci Sports Exerc 1995;27:844–851
    1. Azuma H, Yasuda K, Tohyama H, et al. Timing of administration of transforming growth factor-beta and epidermal growth factor influences the effect on material properties of the in situ frozen-thawed anterior cruciate ligament. J Biomech 2003;36:373–381
    1. Kondo E, Yasuda K, Yamanaka M, Minami A, Tohyama H. Effects of administration of exogenous growth factors on biomechanical properties of the elongation-type anterior cruciate ligament injury with partial laceration. Am J Sports Med 2005;33:188–196
    1. Meaney Murray M, Rice K, Wright RJ, Spector M. The effect of selected growth factors on human anterior cruciate ligament cell interactions with a three-dimensional collagen-GAG scaffold. J Orthop Res 2003;21:238–244
    1. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med 2003;33:381–394
    1. Moreau JE, Chen J, Bramono DS, et al. Growth factor induced fibroblast differentiation from human bone marrow stromal cells in vitro. J Orthop Res 2005;23:164–174
    1. Nagumo A, Yasuda K, Numazaki H, et al. Effects of separate application of three growth factors (TGF-beta1, EGF, and PDGF-BB) on mechanical properties of the in situ frozen-thawed anterior cruciate ligament. Clin Biomech (Bristol, Avon) 2005;20:283–290
    1. Sakai T, Yasuda K, Tohyama H, et al. Effects of combined administration of transforming growth factor-beta1 and epidermal growth factor on properties of the in situ frozen anterior cruciate ligament in rabbits. J Orthop Res 2002;20:1345–1351
    1. Scherping SC Jr, Schmidt CC, Georgescu HI, et al. Effect of growth factors on the proliferation of ligament fibroblasts from skeletally mature rabbits. Connect Tissue Res 1997;36:1–8
    1. Spindler KP, Murray MM, Detwiler KB, et al. The biomechanical response to doses of TGF-beta 2 in the healing rabbit medial collateral ligament. J Orthop Res 2003;21:245–249
    1. Vavken P, Saad FA, Fleming BC, Murray MM. VEGF receptor mRNA expression by ACL fibroblasts is associated with functional healing of the ACL. Knee Surg Sports Traumatol Arthrosc 2011;19:1675–1682
    1. Marui T, Niyibizi C, Georgescu HI, et al. Effect of growth factors on matrix synthesis by ligament fibroblasts. J Orthop Res 1997;15:18–23
    1. Kobayashi D, Kurosaka M, Yoshiya S, Mizuno K. Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc 1997;5:189–194
    1. Cole BJ, Seroyer ST, Filardo G, Bajaj S, Fortier LA. Platelet-rich plasma: where are we now and where are we going? Sports Health 2010;2:203–210
    1. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004;114:1502–1508
    1. McCarrel T, Fortier L. Temporal growth factor release from platelet-rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression. J Orthop Res 2009;27:1033–1042
    1. Mishra A, Woodall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med 2009;28:113–125
    1. Schnabel LV, Mohammed HO, Miller BJ, et al. Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons. J Orthop Res 2007;25:230–240
    1. Vavken P, Sadoghi P, Murray MM. The effect of platelet concentrates on graft maturation and graft-bone interface healing in anterior cruciate ligament reconstruction in human patients: a systematic review of controlled trials. Arthroscopy 2011;27:1573–1583
    1. Weibrich G, Kleis WK, Hafner G, Hitzler WE. Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. J Craniomaxillofac Surg 2002;30:97–102
    1. Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 1997;89:3503–3521
    1. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009;37:1528–1542
    1. Nin JR, Gasque GM, Azcarate AV, Beola JD, Gonzalez MH. Has platelet-rich plasma any role in anterior cruciate ligament allograft healing? Arthroscopy 2009;25:1206–1213
    1. 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;24:1373–1380
    1. Sanchez M, Anitua E, Azofra J, et al. Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology. Arthroscopy 2010;26:470–480
    1. Silva A, Sampaio R. Anatomic ACL reconstruction: does the platelet-rich plasma accelerate tendon healing? Knee Surg Sports Traumatol Arthrosc 2009;17:676–682
    1. 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;45:77–85
    1. Joshi SM, Mastrangelo AN, Magarian EM, Fleming BC, Murray MM. Collagen-platelet composite enhances biomechanical and histologic healing of the porcine anterior cruciate ligament. Am J Sports Med 2009;37:2401–2410
    1. Murray MM, Spindler KP, Abreu E, et al. Collagen-platelet rich plasma hydrogel enhances primary repair of the porcine anterior cruciate ligament. J Orthop Res 2007;25:81–91
    1. Murray MM, Spindler KP, Devin C, et al. Use of a collagen-platelet rich plasma scaffold to stimulate healing of a central defect in the canine ACL. J Orthop Res 2006;24:820–830
    1. Spindler KP, Murray MM, Devin C, Nanney LB, Davidson JM. The central ACL defect as a model for failure of intra-articular healing. J Orthop Res 2006;24:401–406
    1. Drury JL, Mooney DJ. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 2003;24:4337–4351
    1. Kim BS, Putnam AJ, Kulik TJ, Mooney DJ. Optimizing seeding and culture methods to engineer smooth muscle tissue on biodegradable polymer matrices. Biotechnol Bioeng 1998;57:46–54
    1. Berry SM, Green MH. Hyaluronan: a potential carrier for growth factors for the healing of ligamentous tissues. Wound Repair Regen 1997;5:33–38
    1. Wiig ME, Amiel D, VandeBerg J, et al. The early effect of high molecular weight hyaluronan (hyaluronic acid) on anterior cruciate ligament healing: an experimental study in rabbits. J Orthop Res 1990;8:425–434
    1. Dunn MG, Liesch JB, Tiku ML, Zawadsky JP. Development of fibroblast-seeded ligament analogs for ACL reconstruction. J Biomed Mater Res 1995;29:1363–1371
    1. Badylak S, Arnoczky S, Plouhar P, et al. Naturally occurring extracellular matrix as a scaffold for musculoskeletal repair. Clin Orthop Relat Res 1999;367(Suppl):S333–S343
    1. Badylak SF, Park K, Peppas N, McCabe G, Yoder M. Marrow-derived cells populate scaffolds composed of xenogeneic extracellular matrix. Exp Hematol 2001;29:1310–1318
    1. Badylak SF, Tullius R, Kokini K, et al. The use of xenogeneic small intestinal submucosa as a biomaterial for Achilles tendon repair in a dog model. J Biomed Mater Res 1995;29:977–985
    1. Dejardin LM, Arnoczky SP, Ewers BJ, Haut RC, Clarke RB. Tissue-engineered rotator cuff tendon using porcine small intestine submucosa: histologic and mechanical evaluation in dogs. Am J Sports Med 2001;29:175–184
    1. McDevitt CA, Wildey GM, Cutrone RM. Transforming growth factor-beta1 in a sterilized tissue derived from the pig small intestine submucosa. J Biomed Mater Res A 2003;67:637–640
    1. Musahl V, Abramowitch SD, Gilbert TW, et al. The use of porcine small intestinal submucosa to enhance the healing of the medial collateral ligament: a functional tissue engineering study in rabbits. J Orthop Res 2004;22:214–220
    1. Fisher MB, Liang R, Jung HJ, et al. Potential of healing a transected anterior cruciate ligament with genetically modified extracellular matrix bioscaffolds in a goat model. Knee Surg Sports Traumatol Arthrosc 2012;20:1357–1365
    1. Fleming BC, Magarian EM, Harrison SL, Paller DJ, Murray MM. Collagen scaffold supplementation does not improve the functional properties of the repaired anterior cruciate ligament. J Orthop Res 2010;28:703–709
    1. Vavken P, Fleming BC, Mastrangelo AN, Machan JT, Murray MM. Biomechanical outcomes after bioenhanced anterior cruciate ligament repair and anterior cruciate ligament reconstruction are equal in a porcine model. Arthroscopy 2012;28:672–680
    1. Murray MM, Palmer M, Abreu E, et al. Platelet-rich plasma alone is not sufficient to enhance suture repair of the ACL in skeletally immature animals: an in vivo study. J Orthop Res 2009;27:639–645
    1. Frank C, Amiel D, Akeson WH. Healing of the medial collateral ligament of the knee: a morphological and biochemical assessment in rabbits. Acta Orthop Scand 1983;54:917–923
    1. Lo IK, Marchuk LL, Hart DA, Frank CB. Comparison of mRNA levels for matrix molecules in normal and disrupted human anterior cruciate ligaments using reverse transcription-polymerase chain reaction. J Orthop Res 1998;16:421–428
    1. Murray MM, Martin SD, Martin TL, Spector M. Histological changes in the human anterior cruciate ligament after rupture. J Bone Joint Surg [Am] 2000;82-A:1387–1397
    1. Spindler KP, Clark SW, Nanney LB, Davidson JM. Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament: an in situ hybridization study. J Orthop Res 1996;14:857–861
    1. Witonski D, Wagrowska-Danilewicz M. Distribution of substance-P nerve fibers in intact and ruptured human anterior cruciate ligament: a semi-quantitative immunohistochemical assessment. Knee Surg Sports Traumatol Arthrosc 2004;12:497–502
    1. Magarian EM, Fleming BC, Harrison SL, et al. Delay of 2 or 6 weeks adversely affects the functional outcome of augmented primary repair of the porcine anterior cruciate ligament. Am J Sports Med 2010;38:2528–2534
    1. Murray MM, Fleming BC. Use of a bioactive scaffold to stimulate anterior cruciate ligament healing also minimizes posttraumatic osteoarthritis after surgery. Am J Sports Med 2013;41:1762–1770
    1. Vavken P, Proffen B, Peterson C, et al. Effects of suture choice on biomechanics and physeal status after bioenhanced anterior cruciate ligament repair in skeletally immature patients: a large-animal study. Arthroscopy 2013;29:122–132

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