Research progress on bioactive strategies for promoting tendon graft healing after anterior cruciate ligament reconstruction_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CAI Wufeng ,  LI Jian ,  LI Qi

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan Chengdu, 610041, P. R. China;

Corresponding author：

LI Jian, Email: hxlijian@163.com; LI Qi, Email: liqi_sports@scu.edu.cn

Keywords：

Anterior cruciate ligament injury; bioactive strategy; tendon-bone healing; graft ligamentization

DOI：

10.7507/1002-1892.202306088

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the bioactive strategies that enhance tendon graft healing after anterior cruciate ligament reconstruction (ACLR), and to provide insights for improving the therapeutic outcomes of ACLR. Methods The domestic and foreign literature related to the bioactive strategies for promoting the healing of tendon grafts after ACLR was extensively reviewed and summarized. Results At present, there are several kinds of bioactive materials related to tendon graft healing after ACLR: growth factors, cells, biodegradable implants/tissue derivatives. By constructing a complex interface simulating the matrix, environment, and regulatory factors required for the growth of native anterior cruciate ligament (ACL), the growth of transplanted tendons is regulated at different levels, thus promoting the healing of tendon grafts. Although the effectiveness of ACLR has been significantly improved in most studies, most of them are still limited to the early stage of animal experiments, and there is still a long way to go from the real clinical promotion. In addition, limited by the current preparation technology, the bionics of the interface still stays at the micron and millimeter level, and tends to be morphological bionics, and the research on the signal mechanism pathway is still insufficient.Conclusion With the further study of ACL anatomy, development, and the improvement of preparation technology, the research of bioactive strategies to promote the healing of tendon grafts after ACLR is expected to be further promoted.

Citation： CAI Wufeng, LI Jian, LI Qi. Research progress on bioactive strategies for promoting tendon graft healing after anterior cruciate ligament reconstruction. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(10): 1292-1299. doi: 10.7507/1002-1892.202306088 Copy

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2. Diermeier TA, Rothrauff BB, Engebretsen L, et al. Treatment after ACL injury: Panther Symposium ACL Treatment Consensus Group. Br J Sports Med, 2021, 55(1): 14-22.
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6. Andernord D, Karlsson J, Musahl V, et al. Timing of surgery of the anterior cruciate ligament. Arthroscopy, 2013, 29(11): 1863-1871.
7. Sheean AJ, Musahl V, Slone HS, et al. Quadriceps tendon autograft for arthroscopic knee ligament reconstruction: use it now, use it often. Br J Sports Med, 2018, 52(11): 698-701.
8. Renström PA. Eight clinical conundrums relating to anterior cruciate ligament (ACL) injury in sport: recent evidence and a personal reflection. Br J Sports Med, 2013, 47(6): 367-372.
9. He X, Li Y, Guo J, et al. Biomaterials developed for facilitating healing outcome after anterior cruciate ligament reconstruction: Efficacy, surgical protocols, and assessments using preclinical animal models. Biomaterials, 2021, 269: 120625.
10. Yao S, Yung PSH, Lui PPY. Tackling the challenges of graft healing after anterior cruciate ligament reconstruction-thinking from the endpoint. Front Bioeng Biotechnol, 2021, 9: 756930.
11. Ménétrey J, Duthon VB, Laumonier T, et al. “Biological failure” of the anterior cruciate ligament graft. Knee Surg Sports Traumatol Arthrosc, 2008, 16(3): 224-231.
12. Smatov S, Mukasheva F, Erisken C. Collagen fibril diameter distribution of sheep anterior cruciate ligament. Polymers (Basel), 2023, 15(3): 752.
13. Kim HM, Galatz LM, Das R, et al. The role of transforming growth factor beta isoforms in tendon-to-bone healing. Connect Tissue Res, 2011, 52(2): 87-98.
14. Samukawa M, Tohyama H, Yasuda K. Future challenges of anterior cruciate ligament reconstruction biological modulation using a growth factor application for enhancement of graft healing//Ochi M, Shino K, Yasuda K, et al. ACl injury and its treatment. Tokyo: Springer Japan, 2016: 523-536.
15. Crispim JF, Fu SC, Lee YW, et al. Bioactive tape with BMP-2 binding peptides captures endogenous growth factors and accelerates healing after anterior cruciate ligament reconstruction. Am J Sports Med, 2018, 46(12): 2905-2914.
16. Deng XH, Lebaschi A, Camp CL, et al. Expression of signaling molecules involved in embryonic development of the insertion site is inadequate for reformation of the native enthesis: evaluation in a novel murine ACL reconstruction model. J Bone Joint Surg (Am), 2018, 100(15): e102.
17. Blitz E, Sharir A, Akiyama H, et al. Tendon-bone attachment unit is formed modularly by a distinct pool of Scx- and Sox9-positive progenitors. Development, 2013, 140(13): 2680-2690.
18. Zhang Q, Ji Q, Wang X, et al. SOX9 is a regulator of ADAMTSs-induced cartilage degeneration at the early stage of human osteoarthritis. Osteoarthritis Cartilage, 2015, 23(12): 2259-2268.
19. Schwartz AG, Long F, Thomopoulos S. Enthesis fibrocartilage cells originate from a population of Hedgehog-responsive cells modulated by the loading environment. Development, 2015, 142(1): 196-206.
20. Adouni M, Gouissem A, Al Khatib F, et al. Biomechanics of the anterior cruciate ligament under simulated molecular degradation. Eur Cell Mater, 2022, 43: 22-38.
21. Fang F, Sup M, Luzzi A, et al. Hedgehog signaling underlying tendon and enthesis development and pathology. Matrix Biol, 2022, 105: 87-103.
22. Bobzin L, Roberts RR, Chen HJ, et al. Development and maintenance of tendons and ligaments. Development, 2021, 148(8): dev186916.
23. Muller B, Bowman KF, Bedi A. ACL graft healing and biologics. Clin Sports Med, 2013, 32(1): 93-109.
24. Asahara H, Inui M, Lotz MK. Tendons and ligaments: Connecting developmental biology to musculoskeletal disease pathogenesis. J Bone Miner Res, 2017, 32(9): 1773-1782.
25. Pauzenberger L, Syré S, Schurz M. “Ligamentization” in hamstring tendon grafts after anterior cruciate ligament reconstruction: a systematic review of the literature and a glimpse into the future. Arthroscopy, 2013, 29(10): 1712-1721.
26. Little D, Thompson JW, Dubois LG, et al. Proteomic differences between male and female anterior cruciate ligament and patellar tendon. PLoS One, 2014, 9(5): e96526.
27. Scheffler SU, Unterhauser FN, Weiler A. Graft remodeling and ligamentization after cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc, 2008, 16(9): 834-842.
28. Mascarenhas R, Saltzman BM, Sayegh ET, et al. Bioabsorbable versus metallic interference screws in anterior cruciate ligament reconstruction: a systematic review of overlapping meta-analyses. Arthroscopy, 2015, 31(3): 561-568.
29. Naraoka T, Kimura Y, Tsuda E, et al. Is remnant preservation truly beneficial to anterior cruciate ligament reconstruction healing? Clinical and magnetic resonance imaging evaluations of remnant-preserved reconstruction. Am J Sports Med, 2017, 45(5): 1049-1058.
30. Rodeo SA, Arnoczky SP, Torzilli PA, et al. Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg (Am), 1993, 75(12): 1795-1803.
31. Maerz T, Sherman E, Newton M, et al. Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post-traumatic osteoarthritis. J Orthop Res, 2018, 36(7): 1969-1979.
32. Zou J, Yang W, Cui W, et al. Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing. J Nanobiotechnology, 2023, 21(1): 14.
33. Rodríguez-Merchán EC. Anterior cruciate ligament reconstruction: Is biological augmentation beneficial? Int J Mol Sci, 2021, 22(22): 12566. doi: 10.3390/ijms222212566.
34. Kim JH, Oh SH, Min HK, et al. Dual growth factor-immobilized a symmetrically porous membrane for bone-to-tendon interface regeneration on rat patellar tendon avulsion model. J Biomed Mater Res, 2018, 106(1): 115-125.
35. Phillips JE, Burns KL, Le Doux JM, et al. Engineering graded tissue interfaces. Proc Natl Acad Sci U S A, 2008, 105(34): 12170-12175.
36. Madhurakkat Perikamana SK, Lee J, Ahmad T, et al. Harnessing biochemical and structural cues for tenogenic differentiation of adipose derived stem cells (ADSCs) and development of an in vitro tissue interface mimicking tendon-bone insertion graft. Biomaterials, 2018, 165: 79-93.
37. Wang D, Zhang X, Ng KW, et al. Growth and differentiation factor-7 immobilized, mechanically strong quadrol-hexamethylene diisocyanate-methacrylic anhydride polyurethane polymer for tendon repair and regeneration. Acta Biomater, 2022, 154: 108-122.
38. Chen C, Shi Q, Li M, et al. Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers. Bioact Mater, 2022, 16: 451-471.
39. Zhu M, Lin Tay M, Lim KS, et al. Novel growth factor combination for improving rotator cuff repair: A rat in vivo study. Am J Sports Med, 2022, 50(4): 1044-1053.
40. Chen L, Liu J, Guan M, et al. Growth factor and its polymer scaffold-based delivery system for cartilage tissue engineering. Int J Nanomedicine, 2020, 15: 6097-6111.
41. Lyu J, Chen L, Zhang J, et al. A microfluidics-derived growth factor gradient in a scaffold regulates stem cell activities for tendon-to-bone interface healing. Biomater Sci, 2020, 8(13): 3649-3663.
42. Fleming BC, Magarian EM, Harrison SL, et al. Collagen scaffold supplementation does not improve the functional properties of the repaired anterior cruciate ligament. J Orthop Res, 2010, 28(6): 703-709.
43. 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(8): 1762-1770.
44. Jang KM, Lim HC, Jung WY, et al. Efficacy and safety of human umbilical cord blood-derived mesenchymal stem cells in anterior cruciate ligament reconstruction of a rabbit model: New strategy to enhance tendon graft healing. Arthroscopy, 2015, 31(8): 1530-1539.
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