ACL Injury and Its Treatment pp 537-548 | Cite as
Strategies to Enhance Biological Tendon-Bone Healing in Anterior Cruciate Ligament Reconstruction
Abstract
Tissue engineering techniques to enhance tendon-bone healing in anterior cruciate ligament (ACL) reconstruction, including stem cells and growth factors/cytokines, are gaining wide acceptance, and their clinical feasibility has also been recognized. Among them, vascular stem cells at the site of ruptured ACL, which have high proliferation and multi-differentiation potential, accelerate tendon-bone healing by enhancing angiogenesis and osteogenesis in human-rat xenotransplantation and canine autologous transplantation model of ACL reconstruction. A pilot clinical study, which used ruptured tissue for ACL reconstruction, indicated reduction of tunnel enlargement despite no improvement in clinical scores. However, for effective clinical application in future, detailed analysis is required regarding enrolled patient demographic parameters, such as age, sex, surgical timing, and type of ACL injury. This chapter highlights effectiveness of vascular stem cells application for early tendon-bone healing in ACL reconstruction, providing an insight for future strategies.
Keywords
Tendon-bone healing Stem cells Ruptured tissue Angiogenesis OsteogenesisReferences
- 1.Beynnon BD, Johnson RJ, Abate JA, Fleming BC, Nichols CE (2005) Treatment of anterior cruciate ligament injuries, part I. Am J Sports Med 33(10):1579–1602. doi: 10.1177/0363546505279913 PubMedCrossRefGoogle Scholar
- 2.Sundar S, Pendegrass CJ, Blunn GW (2009) Tendon bone healing can be enhanced by demineralized bone matrix: a functional and histological study. J Biomed Mater Res B Appl Biomater 88(1):115–122. doi: 10.1002/jbm.b.31157 PubMedCrossRefGoogle Scholar
- 3.Aglietti P, Giron F, Buzzi R, Biddau F, Sasso F (2004) Anterior cruciate ligament reconstruction: bone-patellar tendon-bone compared with double semitendinosus and gracilis tendon grafts. A prospective, randomized clinical trial. J Bone Joint Surg Am 86-A(10):2143–2155. doi:86/10/2143 [pii]PubMedGoogle Scholar
- 4.Bach BR Jr, Tradonsky S, Bojchuk J, Levy ME, Bush-Joseph CA, Khan NH (1998) Arthroscopically assisted anterior cruciate ligament reconstruction using patellar tendon autograft. Five- to nine-year follow-up evaluation. Am J Sports Med 26(1):20–29PubMedGoogle Scholar
- 5.Beynnon BD, Johnson RJ, Fleming BC, Kannus P, Kaplan M, Samani J, Renstrom P (2002) Anterior cruciate ligament replacement: comparison of bone-patellar tendon-bone grafts with two-strand hamstring grafts. A prospective, randomized study. J Bone Joint Surg Am 84-A(9):1503–1513PubMedGoogle Scholar
- 6.Fu FH, Shen W, Starman JS, Okeke N, Irrgang JJ (2008) Primary anatomic double-bundle anterior cruciate ligament reconstruction: a preliminary 2-year prospective study. Am J Sports Med 36(7):1263–1274. doi: 10.1177/0363546508314428 PubMedCrossRefGoogle Scholar
- 7.Fujita N, Kuroda R, Matsumoto T, Yamaguchi M, Yagi M, Matsumoto A, Kubo S, Matsushita T, Hoshino Y, Nishimoto K, Araki D, Kurosaka M (2011) Comparison of the clinical outcome of double-bundle, anteromedial single-bundle, and posterolateral single-bundle anterior cruciate ligament reconstruction using hamstring tendon graft with minimum 2-year follow-up. Arthroscopy 27(7):906–913. doi: 10.1016/j.arthro.2011.02.015 PubMedCrossRefGoogle Scholar
- 8.Muneta T, Koga H, Mochizuki T, Ju YJ, Hara K, Nimura A, Yagishita K, Sekiya I (2007) A prospective randomized study of 4-strand semitendinosus tendon anterior cruciate ligament reconstruction comparing single-bundle and double-bundle techniques. Arthroscopy 23(6):618–628. doi: 10.1016/j.arthro.2007.04.010 PubMedCrossRefGoogle Scholar
- 9.Yasuda K, Kondo E, Ichiyama H, Kitamura N, Tanabe Y, Tohyama H, Minami A (2004) Anatomic reconstruction of the anteromedial and posterolateral bundles of the anterior cruciate ligament using hamstring tendon grafts. Arthroscopy 20(10):1015–1025. doi: 10.1016/j.arthro.2004.08.010 PubMedCrossRefGoogle Scholar
- 10.Ballock RT, Woo SL, Lyon RM, Hollis JM, Akeson WH (1989) Use of patellar tendon autograft for anterior cruciate ligament reconstruction in the rabbit: a long-term histologic and biomechanical study. J Orthop Res 7(4):474–485. doi: 10.1002/jor.1100070404 PubMedCrossRefGoogle Scholar
- 11.Grana WA, Egle DM, Mahnken R, Goodhart CW (1994) An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med 22(3):344–351PubMedCrossRefGoogle Scholar
- 12.Weiss JA, Woo SL, Ohland KJ, Horibe S, Newton PO (1991) Evaluation of a new injury model to study medial collateral ligament healing: primary repair versus nonoperative treatment. J Orthop Res 9(4):516–528PubMedCrossRefGoogle Scholar
- 13.Woo SL, Inoue M, McGurk-Burleson E, Gomez MA (1987) Treatment of the medial collateral ligament injury. II: structure and function of canine knees in response to differing treatment regimens. Am J Sports Med 15(1):22–29PubMedCrossRefGoogle Scholar
- 14.Fauno P, Kaalund S (2005) Tunnel widening after hamstring anterior cruciate ligament reconstruction is influenced by the type of graft fixation used: a prospective randomized study. Arthroscopy 21(11):1337–1341. doi:S0749-8063(05)01186-2 [pii] 10.1016/j.arthro.2005.08.023 PubMedCrossRefGoogle Scholar
- 15.L’Insalata JC, Klatt B, Fu FH, Harner CD (1997) Tunnel expansion following anterior cruciate ligament reconstruction: a comparison of hamstring and patellar tendon autografts. Knee Surg Sports Traumatol Arthrosc 5(4):234–238PubMedCrossRefGoogle Scholar
- 16.Ekdahl M, Nozaki M, Ferretti M, Tsai A, Smolinski P, Fu FH (2009) The effect of tunnel placement on bone-tendon healing in anterior cruciate ligament reconstruction in a goat model. Am J Sports Med 37(8):1522–1530. doi:0363546509332503 [pii] 10.1177/0363546509332503 PubMedCrossRefGoogle Scholar
- 17.Getelman MH, Friedman MJ (1999) Revision anterior cruciate ligament reconstruction surgery. J Am Acad Orthop Surg 7(3):189–198PubMedCrossRefGoogle Scholar
- 18.Petrigliano FA, McAllister DR, Wu BM (2006) Tissue engineering for anterior cruciate ligament reconstruction: a review of current strategies. Arthroscopy 22(4):441–451. doi:S0749-8063(06)00109-5 [pii] 10.1016/j.arthro.2006.01.017 PubMedCrossRefGoogle Scholar
- 19.Chen CH, Chen WJ, Shih CH, Yang CY, Liu SJ, Lin PY (2003) Enveloping the tendon graft with periosteum to enhance tendon-bone healing in a bone tunnel: a biomechanical and histologic study in rabbits. Arthroscopy 19(3):290–296. doi: 10.1053/jars.2003.50014 PubMedCrossRefGoogle Scholar
- 20.Karaoglu S, Celik C, Korkusuz P (2009) The effects of bone marrow or periosteum on tendon-to-bone tunnel healing in a rabbit model. Knee Surg Sports Traumatol Arthrosc 17(2):170–178. doi: 10.1007/s00167-008-0646-3 PubMedCrossRefGoogle Scholar
- 21.Ouyang HW, Goh JC, Lee EH (2004) Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model. Am J Sports Med 32(2):321–327PubMedCrossRefGoogle Scholar
- 22.Lim JK, Hui J, Li L, Thambyah A, Goh J, Lee EH (2004) Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction. Arthroscopy 20(9):899–910. doi: 10.1016/j.arthro.2004.06.035 PubMedCrossRefGoogle Scholar
- 23.Huangfu X, Zhao J (2007) Tendon-bone healing enhancement using injectable tricalcium phosphate in a dog anterior cruciate ligament reconstruction model. Arthroscopy 23(5):455–462. doi: 10.1016/j.arthro.2006.12.031 PubMedCrossRefGoogle Scholar
- 24.Anderson K, Seneviratne AM, Izawa K, Atkinson BL, Potter HG, Rodeo SA (2001) Augmentation of tendon healing in an intraarticular bone tunnel with use of a bone growth factor. Am J Sports Med 29(6):689–698PubMedGoogle Scholar
- 25.Nakase J, Kitaoka K, Matsumoto K, Tomita K (2010) Facilitated tendon-bone healing by local delivery of recombinant hepatocyte growth factor in rabbits. Arthroscopy 26(1):84–90. doi: 10.1016/j.arthro.2009.06.029 PubMedCrossRefGoogle Scholar
- 26.Rodeo SA, Suzuki K, Deng XH, Wozney J, Warren RF (1999) Use of recombinant human bone morphogenetic protein-2 to enhance tendon healing in a bone tunnel. Am J Sports Med 27(4):476–488PubMedGoogle Scholar
- 27.Sasaki K, Kuroda R, Ishida K, Kubo S, Matsumoto T, Mifune Y, Kinoshita K, Tei K, Akisue T, Tabata Y, Kurosaka M (2008) Enhancement of tendon-bone osteointegration of anterior cruciate ligament graft using granulocyte colony-stimulating factor. Am J Sports Med 36(8):1519–1527. doi: 10.1177/0363546508316282 PubMedCrossRefGoogle Scholar
- 28.Yoshikawa T, Tohyama H, Katsura T, Kondo E, Kotani Y, Matsumoto H, Toyama Y, Yasuda K (2006) Effects of local administration of vascular endothelial growth factor on mechanical characteristics of the semitendinosus tendon graft after anterior cruciate ligament reconstruction in sheep. Am J Sports Med 34(12):1918–1925PubMedCrossRefGoogle Scholar
- 29.Frank CB, Jackson DW (1997) The science of reconstruction of the anterior cruciate ligament. J Bone Joint Surg Am 79(10):1556–1576PubMedGoogle Scholar
- 30.Murray MM, Martin SD, Martin TL, Spector M (2000) Histological changes in the human anterior cruciate ligament after rupture. J Bone Joint Surg Am 82-A(10):1387–1397PubMedGoogle Scholar
- 31.Fujimoto E, Sumen Y, Ochi M, Ikuta Y (2002) Spontaneous healing of acute anterior cruciate ligament (ACL) injuries – conservative treatment using an extension block soft brace without anterior stabilization. Arch Orthop Trauma Surg 122(4):212–216PubMedCrossRefGoogle Scholar
- 32.Kurosaka M, Yoshiya S, Mizuno T, Mizuno K (1998) Spontaneous healing of a tear of the anterior cruciate ligament. A report of two cases. J Bone Joint Surg Am 80(8):1200–1203PubMedGoogle Scholar
- 33.Sandberg R, Balkfors B, Nilsson B, Westlin N (1987) Operative versus non-operative treatment of recent injuries to the ligaments of the knee. A prospective randomized study. J Bone Joint Surg Am 69(8):1120–1126PubMedGoogle Scholar
- 34.Drogset JO, Grontvedt T, Robak OR, Molster A, Viset AT, Engebretsen L (2006) A sixteen-year follow-up of three operative techniques for the treatment of acute ruptures of the anterior cruciate ligament. J Bone Joint Surg Am 88(5):944–952. doi:88/5/944 [pii] 10.2106/JBJS.D.02876 PubMedCrossRefGoogle Scholar
- 35.Marshall JL, Warren RF, Wickiewicz TL (1982) Primary surgical treatment of anterior cruciate ligament lesions. Am J Sports Med 10(2):103–107PubMedCrossRefGoogle Scholar
- 36.Marshall JL, Warren RF, Wickiewicz TL, Reider B (1979) The anterior cruciate ligament: a technique of repair and reconstruction. Clin Orthop Relat Res 143:97–106PubMedGoogle Scholar
- 37.Strand T, Molster A, Hordvik M, Krukhaug Y (2005) Long-term follow-up after primary repair of the anterior cruciate ligament: clinical and radiological evaluation 15–23 years postoperatively. Arch Orthop Trauma Surg 125(4):217–221. doi: 10.1007/s00402-004-0766-2 PubMedCrossRefGoogle Scholar
- 38.Lee IC, Wang JH, Lee YT, Young TH (2007) Development of a useful technique to discriminate anterior cruciate ligament cells and mesenchymal stem cells-the application of cell electrophoresis. J Biomed Mater Res A 82(1):230–237. doi: 10.1002/jbm.a.31163 PubMedCrossRefGoogle Scholar
- 39.Lee SY, Miwa M, Sakai Y, Kuroda R, Matsumoto T, Iwakura T, Fujioka H, Doita M, Kurosaka M (2007) In vitro multipotentiality and characterization of human unfractured traumatic hemarthrosis-derived progenitor cells: a potential cell source for tissue repair. J Cell Physiol 210(3):561–566. doi: 10.1002/jcp.20890 PubMedCrossRefGoogle Scholar
- 40.Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313. doi:S1934-5909(08)00337-8 [pii] 10.1016/j.stem.2008.07.003 PubMedCrossRefGoogle Scholar
- 41.Howson KM, Aplin AC, Gelati M, Alessandri G, Parati EA, Nicosia RF (2005) The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture. Am J Physiol Cell Physiol 289(6):C1396–C1407. doi:00168.2005 [pii] 10.1152/ajpcell.00168.2005 PubMedCrossRefGoogle Scholar
- 42.Tavian M, Zheng B, Oberlin E, Crisan M, Sun B, Huard J, Peault B (2005) The vascular wall as a source of stem cells. Ann N Y Acad Sci 1044:41–50PubMedCrossRefGoogle Scholar
- 43.Zengin E, Chalajour F, Gehling UM, Ito WD, Treede H, Lauke H, Weil J, Reichenspurner H, Kilic N, Ergun S (2006) Vascular wall resident progenitor cells: a source for postnatal vasculogenesis. Development 133(8):1543–1551. doi:dev.02315 [pii] 10.1242/dev.02315 PubMedCrossRefGoogle Scholar
- 44.Matsumoto T, Ingham SM, Mifune Y, Osawa A, Logar A, Usas A, Kuroda R, Kurosaka M, Fu FH, Huard J (2012) Isolation and characterization of human anterior cruciate ligament-derived vascular stem cells. Stem Cells Dev 21(6):859–872. doi: 10.1089/scd.2010.0528 PubMedCrossRefGoogle Scholar
- 45.Covas DT, Panepucci RA, Fontes AM, Silva WA Jr, Orellana MD, Freitas MC, Neder L, Santos AR, Peres LC, Jamur MC, Zago MA (2008) Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts. Exp Hematol 36(5):642–654. doi:S0301-472X(08)00005-2 [pii] 10.1016/j.exphem.2007.12.015 PubMedCrossRefGoogle Scholar
- 46.Iwasaki H, Kawamoto A, Ishikawa M, Oyamada A, Nakamori S, Nishimura H, Sadamoto K, Horii M, Matsumoto T, Murasawa S, Shibata T, Suehiro S, Asahara T (2006) Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction. Circulation 113(10):1311–1325PubMedCrossRefGoogle Scholar
- 47.Yeh ET, Zhang S, Wu HD, Korbling M, Willerson JT, Estrov Z (2003) Transdifferentiation of human peripheral blood CD34 + −enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 108(17):2070–2073. doi: 10.1161/01.CIR.0000099501.52718.70 01.CIR.0000099501.52718.70 [pii]PubMedCrossRefGoogle Scholar
- 48.Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147PubMedCrossRefGoogle Scholar
- 49.Martinek V, Latterman C, Usas A, Abramowitch S, Woo SL, Fu FH, Huard J (2002) Enhancement of tendon-bone integration of anterior cruciate ligament grafts with bone morphogenetic protein-2 gene transfer: a histological and biomechanical study. J Bone Joint Surg Am 84-A(7):1123–1131PubMedGoogle Scholar
- 50.Mihelic R, Pecina M, Jelic M, Zoricic S, Kusec V, Simic P, Bobinac D, Lah B, Legovic D, Vukicevic S (2004) Bone morphogenetic protein-7 (osteogenic protein-1) promotes tendon graft integration in anterior cruciate ligament reconstruction in sheep. Am J Sports Med 32(7):1619–1625PubMedCrossRefGoogle Scholar
- 51.Yasuda K, Tomita F, Yamazaki S, Minami A, Tohyama H (2004) The effect of growth factors on biomechanical properties of the bone-patellar tendon-bone graft after anterior cruciate ligament reconstruction: a canine model study. Am J Sports Med 32(4):870–880PubMedCrossRefGoogle Scholar
- 52.Tei K, Matsumoto T, Mifune Y, Ishida K, Sasaki K, Shoji T, Kubo S, Kawamoto A, Asahara T, Kurosaka M, Kuroda R (2008) Administrations of peripheral blood CD34-positive cells contribute to medial collateral ligament healing via vasculogenesis. Stem Cells 26(3):819–830. doi: 10.1634/stemcells.2007-0671 PubMedCrossRefGoogle Scholar
- 53.Matsumoto T, Kawamoto A, Kuroda R, Ishikawa M, Mifune Y, Iwasaki H, Miwa M, Horii M, Hayashi S, Oyamada A, Nishimura H, Murasawa S, Doita M, Kurosaka M, Asahara T (2006) Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. Am J Pathol 169(4):1440–1457. doi: 10.2353/ajpath.2006.060064 PubMedPubMedCentralCrossRefGoogle Scholar
- 54.Mifune Y, Matsumoto T, Kawamoto A, Kuroda R, Shoji T, Iwasaki H, Kwon SM, Miwa M, Kurosaka M, Asahara T (2008) Local delivery of granulocyte colony stimulating factor-mobilized CD34-positive progenitor cells using bioscaffold for modality of unhealing bone fracture. Stem Cells 26(6):1395–1405. doi: 10.1634/stemcells.2007-0820 PubMedCrossRefGoogle Scholar
- 55.Mifune Y, Matsumoto T, Ota S, Nishimori M, Usas A, Kopf S, Kuroda R, Kurosaka M, Fu FH, Huard J (2012) Therapeutic potential of anterior cruciate ligament-derived stem cells for anterior cruciate ligament reconstruction. Cell Transplant 21(8):1651–1665. doi: 10.3727/096368912X647234 PubMedCrossRefGoogle Scholar
- 56.Matsumoto T, Kubo S, Sasaki K, Kawakami Y, Oka S, Sasaki H, Takayama K, Tei K, Matsushita T, Mifune Y, Kurosaka M, Kuroda R (2012) Acceleration of tendon-bone healing of anterior cruciate ligament graft using autologous ruptured tissue. Am J Sports Med 40(6):1296–1302. doi: 10.1177/0363546512439026 PubMedCrossRefGoogle Scholar
- 57.Matsumoto T, Kuroda R, Matsushita T, Araki D, Hoshino Y, Nagamune K, Kurosaka M (2014) Reduction of tunnel enlargement with use of autologous ruptured tissue in anterior cruciate ligament reconstruction: a pilot clinical trial. Arthroscopy 30(4):468–474. doi: 10.1016/j.arthro.2013.12.014 PubMedCrossRefGoogle Scholar
- 58.Chen CH, Chang CH, Su CI, Wang KC, Liu HT, Yu CM, Wong CB, Wang IC (2010) Arthroscopic single-bundle anterior cruciate ligament reconstruction with periosteum-enveloping hamstring tendon graft: clinical outcome at 2 to 7 years. Arthroscopy 26(7):907–917. doi: 10.1016/j.arthro.2009.11.011 PubMedCrossRefGoogle Scholar
- 59.Li H, Jiang J, Wu Y, Chen S (2012) Potential mechanisms of a periosteum patch as an effective and favourable approach to enhance tendon-bone healing in the human body. Int Orthop 36(3):665–669. doi: 10.1007/s00264-011-1346-z PubMedCrossRefGoogle Scholar
- 60.Robert H, Es-Sayeh J (2004) The role of periosteal flap in the prevention of femoral widening in anterior cruciate ligament reconstruction using hamstring tendons. Knee Surg Sports Traumatol Arthrosc 12(1):30–35. doi: 10.1007/s00167-003-0380-9 PubMedCrossRefGoogle Scholar
- 61.Adachi N, Ochi M, Uchio Y, Iwasa J, Ryoke K, Kuriwaka M (2002) Mechanoreceptors in the anterior cruciate ligament contribute to the joint position sense. Acta Orthop Scand 73(3):330–334. doi: 10.1080/000164702320155356 PubMedCrossRefGoogle Scholar
- 62.Ochi M, Abouheif MM, Kongcharoensombat W, Nakamae A, Adachi N, Deie M (2011) Double bundle arthroscopic anterior cruciate ligament reconstruction with remnant preserving technique using a hamstring autograft. Sports Med Arthrosc Rehabil Ther Technol 3:30. doi: 10.1186/1758-2555-3-30 PubMedPubMedCentralCrossRefGoogle Scholar
- 63.Ochi M, Adachi N, Deie M, Kanaya A (2006) Anterior cruciate ligament augmentation procedure with a 1-incision technique: anteromedial bundle or posterolateral bundle reconstruction. Arthroscopy 22(4):463 e461–463 e465. doi: 10.1016/j.arthro.2005.06.034 CrossRefGoogle Scholar
- 64.Ochi M, Adachi N, Uchio Y, Deie M, Kumahashi N, Ishikawa M, Sera S (2009) A minimum 2-year follow-up after selective anteromedial or posterolateral bundle anterior cruciate ligament reconstruction. Arthroscopy 25(2):117–122. doi: 10.1016/j.arthro.2008.10.011 PubMedCrossRefGoogle Scholar
- 65.Yasuda K, Kondo E, Kitamura N, Kawaguchi Y, Kai S, Tanabe Y (2012) A pilot study of anatomic double-bundle anterior cruciate ligament reconstruction with ligament remnant tissue preservation. Arthroscopy 28(3):343–353. doi: 10.1016/j.arthro.2011.08.305 PubMedCrossRefGoogle Scholar
- 66.Uefuji A, Matsumoto T, Matsushita T, Ueha T, Zhang S, Kurosaka M, Kuroda R (2014) Age-related differences in anterior cruciate ligament remnant vascular-derived cells. Am J Sports Med 42(6):1478–1486. doi: 10.1177/0363546514529092 PubMedCrossRefGoogle Scholar
- 67.Nakano N, Matsumoto T, Takayama K, Matsushita T, Araki D, Uefuji A, Nagai K, Zhang S, Inokuchi T, Nishida K, Kuroda R, Kurosaka M (2015) Age-dependent healing potential of anterior cruciate ligament remnant-derived cells. Am J Sports Med 43(3):700–708. doi: 10.1177/0363546514561436 PubMedCrossRefGoogle Scholar