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Materials Enhancing Anterior Cruciate Ligament Tendon Graft to Bone Healing Show Favorable Results, in Animal Models, In Vivo: A Systematic Review

  • Marc Saab
    Correspondence
    Address correspondence to Marc Saab, M.D., CHU Lille, Orthopaedic and Traumatology Department, Hôpital Roger Salengro, F-59000 Lille, France.
    Affiliations
    CHU Lille, Orthopaedic and Traumatology Department, Hôpital Roger Salengro, Lille, France
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  • Feng Hildebrand
    Affiliations
    U1008 Controlled Drug Delivery Systems and Biomaterials, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Lille, University of Lille, Lille, France
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  • Bernard Martel
    Affiliations
    UMR 8207, UMET—Unité Matériaux et Transformations, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Ecole Nationale Supérieure de Chimie de Lille (ENSCL), University of Lille, Lille, France
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  • Nicolas Blanchemain
    Affiliations
    U1008 Controlled Drug Delivery Systems and Biomaterials, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Lille, University of Lille, Lille, France
    Search for articles by this author

      Purpose

      To perform a systematic literature review to analyze the results of the in vivo animal models and strategies that use osteoinductive materials to enhance the tendon graft–bone interface for anterior cruciate ligament reconstruction (ACLR).

      Methods

      Following the Preferred Reporting Items for Systemic Reviews and Meta-Analysis guidelines, the PubMed, Embase, and Web of Science databases were searched. The inclusion criteria were studies of in vivo animal models of ACLR using a material to enhance tendon graft–bone interface healing and reporting at least the histologic results at the interface, along with radiologic and biomechanical data. Studies without control group or with another tendon–bone healing model were excluded. Methodologic quality was assessed with the Animal Research: Reporting In Vivo Experiments 1guidelines.

      Results

      Twenty-seven studies met the inclusion criteria. Rabbit was the main animal model of ACLR, along with sheep and dog models. ACLR procedures varied widely between studies.. The main promising strategies and materials were wrapping the material around the graft, with a collagen scaffold loaded with an osteoinductive molecule (mostly bone morphogenetic proteins). The second strategy consisted of injecting the material at the tendon–bone interface; calcium phosphate cement or a derivative were the most used materials. Finally, using osteoinductive fixation devices was the third strategy; magnesium-based interference screws seemed to show most favorable results.

      Conclusions

      The studies retained had major methodologic flaws that limit the scope of these conclusions. However, based on histologic, biomechanical, and radiologic analyses, the most promising materials were a collagen scaffold loaded with an osteoinductive molecule and wrapped around the graft, calcium phosphate cement injected in the bone tunnel, and a magnesium-based fixation device.

      Clinical Relevance

      In vivo animal models have identified several promising strategies and materials to optimize the tendon–bone interface after ACLR, but standardized and reproducible assessments are needed before these strategies can be adopted clinically.
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      References

        • Griffin L.Y.
        • Albohm M.J.
        • Arendt E.A.
        • 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
        • Lyman S.
        • Koulouvaris P.
        • Sherman S.
        • Do H.
        • Mandl L.A.
        • Marx R.G.
        Epidemiology of anterior cruciate ligament reconstruction trends, readmissions, and subsequent knee surgery.
        J Bone Joint Surg Am. 2009; 91A: 2321-2328
        • Grana W.
        • Egle D.
        • Mahnken R.
        • et al.
        An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model.
        Am J Sports Med. 1994; 22: 344-351
        • Benjamin M.
        • Evans E.J.
        • Copp L.
        The histology of tendon attachments to bone in man.
        J Anat. 1986; 149: 89-100
        • Cooper R.R.
        • Misol S.
        Tendon and ligament insertion. A light and electron microscopic study.
        J Bone Joint Surg Am. 1970; 52: 1-20
        • Rodeo S.
        • Arnoczky S.
        • Torzilli P.
        • Hidaka C.
        • Warren R.
        Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog.
        J Bone Joint Surg Am. 1993; 75: 1795-1803
        • Guo R.
        • Gao L.
        • Xu B.
        Current evidence of adult stem cells to enhance anterior cruciate ligament treatment: A systematic review of animal trials.
        Arthroscopy. 2018; 34: 331-340
        • Martinek V.
        • Latterman C.
        • Usas A.
        • et al.
        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. 2002; 84: 1123-1131
        • Hexter A.T.
        • Pendegrass C.
        • Haddad F.
        • Blunn G.
        Demineralized bone matrix to augment tendon–bone healing: A systematic review.
        Orthop J Sports Med. 2017; 52325967117734517
        • Shamseer L.
        • Moher D.
        • Clarke M.
        • et al.
        Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: Elaboration and explanation.
        BMJ. 2015; 350: g7647
        • Rodeo S.A.
        • Potter H.G.
        • Kawamura S.
        • Turner A.S.
        • Kim H.J.
        • Atkinson B.L.
        Biologic augmentation of rotator cuff tendon–healing with use of a mixture of osteoinductive growth factors.
        J Bone Joint Surg Am. 2007; 89: 2485-2497
        • Höher J.
        • Möller H.D.
        • Fu F.H.
        Bone tunnel enlargement after anterior cruciate ligament reconstruction: Fact or fiction?.
        Knee Surg Sports Traumatol Arthrosc. 1998; 6: 231-240
        • Wilson T.C.
        • Kantaras A.
        • Atay A.
        • Johnson D.L.
        Tunnel enlargement after anterior cruciate ligament surgery.
        Am J Sports Med. 2004; 32: 543-549
        • Clatworthy M.G.
        • Annear P.
        • Bulow J.U.
        • Bartlett R.J.
        Tunnel widening in anterior cruciate ligament reconstruction: A prospective evaluation of hamstring and patella tendon grafts.
        Knee Surg Sports Traumatol Arthrosc. 1999; 7: 138-145
        • du Sert N.P.
        • Ahluwalia A.
        • Alam S.
        • et al.
        Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0.
        PLOS Biol. 2020; 18e3000411
        • Anderson K.
        • Seneviratne A.M.
        • Izawa K.
        • Atkinson B.L.
        • Potter H.G.
        • Rodeo S.A.
        Augmentation of tendon healing in an intraarticular bone tunnel with use of a bone growth factor.
        Am J Sports Med. 2001; 29: 689-698
        • Walsh W.R.
        • Cotton N.J.
        • Stephens P.
        • et al.
        Comparison of poly-L-lactide and polylactide carbonate interference screws in an ovine anterior cruciate ligament reconstruction model.
        Arthroscopy. 2007; 23: 757-765
        • Rodeo S.A.
        • Kawamura S.
        • Ma C.B.
        • et al.
        The effect of osteoclastic activity on tendon-to-bone healing: An experimental study in rabbits.
        J Bone Joint Surg Am. 2007; 89: 2250-2259
        • Gulotta L.V.
        • Kovacevic D.
        • Ying L.
        • Ehteshami J.R.
        • Montgomery S.
        • Rodeo S.A.
        Augmentation of tendon-to-bone healing with a magnesium-based bone adhesive.
        Am J Sports Med. 2008; 36: 1290-1297
        • Mutsuzaki H.
        • Sakane M.
        • Hattori S.
        • Kobayashi H.
        • Ochiai N.
        Firm anchoring between a calcium phosphate-hybridized tendon and bone for anterior cruciate ligament reconstruction in a goat model.
        Biomed Mater Bristol Engl. 2009; 4045013
        • Zhang M.
        • Zhen J.
        • Zhang X.
        • et al.
        Effect of autologous platelet-rich plasma and gelatin sponge for tendon-to-bone healing after rabbit anterior cruciate ligament reconstruction.
        Arthroscopy. 2019; 35: 1486-1497
        • Sasaki K.
        • Kuroda R.
        • Ishida K.
        • et al.
        Enhancement of tendon-bone osteointegration of anterior cruciate ligament graft using granulocyte colony-stimulating factor.
        Am J Sports Med. 2008; 36: 1519-1527
        • Lu D.
        • Yang C.
        • Zhang Z.
        • Xiao M.
        Enhanced tendon-bone healing with acidic fibroblast growth factor delivered in collagen in a rabbit anterior cruciate ligament reconstruction model.
        J Orthop Surg. 2018; 13: 301
        • Kuang G.M.
        • Yau W.P.
        • Lu W.W.
        • Chiu K.Y.
        Local application of strontium in a calcium phosphate cement system accelerates healing of soft tissue tendon grafts in anterior cruciate ligament reconstruction: Experiment using a rabbit model.
        Am J Sports Med. 2014; 42: 2996-3002
        • Cheng P.
        • Han P.
        • Zhao C.
        • et al.
        High-purity magnesium interference screws promote fibrocartilaginous entheses regeneration in the anterior cruciate ligament reconstruction rabbit model via accumulation of BMP-2 and VEGF.
        Biomaterials. 2016; 81: 14-26
        • Mutsuzaki H.
        • Fujie H.
        • Nakajima H.
        • Fukagawa M.
        • Nomura S.
        • Sakane M.
        Effect of calcium phosphate-hybridized tendon graft in anatomic single-bundle ACL reconstruction in goats.
        Orthop J Sports Med. 2016; 42325967116662653
        • Yamazaki S.
        • Yasuda K.
        • Tomita F.
        • Tohyama H.
        • Minami A.
        The effect of transforming growth factor-beta1 on intraosseous healing of flexor tendon autograft replacement of anterior cruciate ligament in dogs.
        Arthroscopy. 2005; 21: 1034-1041
        • Mutsuzaki H.
        • Sakane M.
        • Fujie H.
        • Hattori S.
        • Kobayashi H.
        • Ochiai N.
        Effect of calcium phosphate-hybridized tendon graft on biomechanical behavior in anterior cruciate ligament reconstruction in a goat model novel technique for improving tendon-bone healing.
        Am J Sports Med. 2011; 39: 1059-1066
        • Huangfu X.
        • Zhao J.
        Tendon–bone healing enhancement using injectable tricalcium phosphate in a dog anterior cruciate ligament reconstruction model.
        Arthroscopy. 2007; 23: 455-462
        • Fu Y.M.
        • Yin Y.
        • Guan J.W.
        • Ji Q.B.
        • Wang Y.
        • Zhang Q.
        The evaluation of a degradable Magnesium alloy Bio-Transfix nail system compounded with bone morphogenetic protein-2 in a beagle anterior cruciate ligament reconstruction model.
        J Biomater Appl. 2019; 34: 687-698
        • Mutsuzaki H.
        • Sakane M.
        • Nakajima H.
        • et al.
        Calcium-phosphate-hybridized tendon directly promotes regeneration of tendon–bone insertion.
        J Biomed Mater Res A. 2004; 70: 319-327
        • Wen C.Y.
        • Qin L.
        • Lee K.M.
        • Chan K.M.
        The use of brushite calcium phosphate cement for enhancement of bone–tendon integration in an anterior cruciate ligament reconstruction rabbit model.
        J Biomed Mater Res B Appl Biomater. 2009; 89: 466-474
        • Pan W.
        • Wei Y.
        • Zhou L.
        • Li D.
        Comparative in vivo study of injectable biomaterials combined with bmp for enhancing tendon graft osteointegration for anterior cruciate ligament reconstruction.
        J Orthop Res. 2011; 29: 1015-1021
        • Wei B.
        • Wang C.
        • Yan C.
        • et al.
        Osteoprotegerin/bone morphogenetic protein 2 combining with collagen sponges on tendon–bone healing in rabbits.
        J Bone Miner Metab. 2020; 38: 432-441
        • Han F.
        • Zhang P.
        • Chen T.
        • Lin C.
        • Wen X.
        • Zhao P.
        A LbL-Assembled bioactive coating modified nanofibrous membrane for rapid tendon–bone healing in ACL reconstruction.
        Int J Nanomed. 2019; 14: 9159-9172
        • Mihelic R.
        • Pecina M.
        • Jelic M.
        • et al.
        Bone morphogenetic protein-7 (Osteogenic protein-1) promotes tendon graft integration in anterior cruciate ligament reconstruction in sheep.
        Am J Sports Med. 2004; 32: 1619-1625
        • Oka S.
        • Matsumoto T.
        • Kubo S.
        • et al.
        Local administration of low-dose simvastatin-conjugated gelatin hydrogel for tendon–bone healing in anterior cruciate ligament reconstruction.
        Tissue Eng Part A. 2013; 19: 1233-1243
        • Han F.
        • Zhang P.
        • Sun Y.
        • Lin C.
        • Zhao P.
        • Chen J.
        Hydroxyapatite-doped polycaprolactone nanofiber membrane improves tendon–bone interface healing for anterior cruciate ligament reconstruction.
        Int J Nanomed. 2015; 10: 7333-7343
        • Wang J.
        • Wu Y.
        • Li H.
        • et al.
        Magnesium alloy based interference screw developed for ACL reconstruction attenuates peri-tunnel bone loss in rabbits.
        Biomaterials. 2018; 157: 86-97
        • Sun J.
        • Zhang X.
        • Shi Z.Z.
        • et al.
        Development of a high-strength Zn-Mn-Mg alloy for ligament reconstruction fixation.
        Acta Biomater. 2021; 119: 485-498
        • Ma C.B.
        • Kawamura S.
        • Deng X.H.
        • et al.
        Bone morphogenetic proteins-signaling plays a role in tendon-to-bone healing: A study of rhBMP-2 and noggin.
        Am J Sports Med. 2007; 35: 597-604
        • Tien Y.C.
        • Chih T.T.
        • Lin J.H.C.
        • Ju C.P.
        • Lin S.D.
        Augmentation of tendon–bone healing by the use of calcium-phosphate cement.
        J Bone Joint Surg Br. 2004; 86: 1072-1076
        • Yamakado K.
        • Kitaoka K.
        • Nakamura T.
        • et al.
        Histologic analysis of the tibial bone tunnel after anterior cruciate ligament reconstruction using solvent-dried and gamma-irradiated fascia lata allograft.
        Arthroscopy. 2001; 17 (32-32)
        • Yeh W.L.
        • Lin S.S.
        • Yuan L.J.
        • Lee K.F.
        • Lee M.Y.
        • Ueng S.W.N.
        Effects of hyperbaric oxygen treatment on tendon graft and tendon-bone integration in bone tunnel: Biochemical and histological analysis in rabbits.
        J Orthop Res. 2007; 25: 636-645
        • Kuang G.M.
        • Yau W.P.
        • Lu W.W.
        • Chiu K.Y.
        Use of a strontium-enriched calcium phosphate cement in accelerating the healing of soft-tissue tendon graft within the bone tunnel in a rabbit model of anterior cruciate ligament reconstruction.
        Bone Joint J. 2013; 95B: 923-928
        • Murray M.M.
        • Spindler K.P.
        • Ballard P.
        • Welch T.P.
        • Zurakowski D.
        • Nanney L.B.
        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
        • Song F.
        • Jiang D.
        • Wang T.
        • et al.
        Mechanical loading improves tendon–bone healing in a rabbit anterior cruciate ligament reconstruction model by promoting proliferation and matrix formation of mesenchymal stem cells and tendon cells.
        Cell Physiol Biochem. 2017; 41: 875-889
        • Kilicoglu O.
        • Demirhan M.
        • Akman S.
        • Atalar A.C.
        • Ozsoy S.
        • Ince U.
        Failure strength of bioabsorbable interference screws: Effects of in vivo degradation for 12 weeks.
        Knee Surg Sports Traumatol Arthrosc. 2003; 11: 228-234
        • Radford M.J.
        • Noakes J.
        • Read J.
        • Wood D.G.
        The natural history of a bioabsorbable interference screw used for anterior cruciate ligament reconstruction with a 4-strand hamstring technique.
        Arthroscopy. 2005; 21: 707-710
        • Achtnich A.
        • Forkel P.
        • Metzlaff S.
        • Zantop T.
        • Petersen W.
        Degradation of poly-d-l-lactide (PDLLA) interference screws (Megafix®).
        Arch Orthop Trauma Surg. 2014; 134: 1147-1153
        • Wong C.C.
        • Wong P.C.
        • Tsai P.H.
        • et al.
        Biocompatibility and osteogenic capacity of Mg-Zn-Ca bulk metallic glass for rabbit tendon–bone interference fixation.
        Int J Mol Sci. 2019; 20
        • Mutsuzaki H.
        • Kinugasa T.
        • Ikeda K.
        • Sakane M.
        Anatomic single-bundle anterior cruciate ligament reconstruction using a calcium phosphate-hybridized tendon graft: A randomized controlled trial with 2years of follow-up.
        J Orthop Surg. 2018; 13: 327
        • Lai W.C.
        • Iglesias B.C.
        • Mark B.J.
        • Wang D.
        Low-intensity pulsed ultrasound augments tendon, ligament, and bone-soft tissue healing in preclinical animal models: A systematic review.
        Arthroscopy. 2021; 37: 2318-2333.e3