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Ligament Biology and Healing

54 citationsUpdated Oct 2026
Illustration: Ligament Biology and Healing

Overview

Ligament and tendon healing remains a complex biological process where current therapies aim to enhance efficacy rather than achieve true regeneration [1]. The intrinsic healing capacity varies significantly by anatomical site; for instance, the ACL has limited capability to heal due to a lack of localized hematoma and low reparative cell supply [7], whereas extra-articular ligaments like the MCL heal spontaneously but with poor mechanical properties [7]. Conversely, the radioscapholunate ligament possesses a vascular supply that may be sufficient for healing by known methods [6]. While bleeding at the injury site is associated with an increased healing response, evidenced by increased macrophage counts and collagen gene expression, biomechanical testing did not demonstrate functional differences in ligament healing despite the presence of bleeding [2]. Early ligament function after repair depends on the cellular population of the repair, while early graft function after reconstruction depends on the maintenance of organized collagen [4].

Despite remodelling, grafts retain a deficit in tensile strength and stiffness compared to the original ligament, a deficit that may explain high failure rates in the first year [12]. Understanding spatial and time-dependent changes in graft healing is important for developing strategies to achieve full restoration of function and mechanical strength in cruciate ligament surgery [5]. Early controlled motion of stable or surgically stabilized joints appears to improve ligament scar behavior [3], yet no treatment identified to date stimulates true ligament regeneration [3]. Biologic approaches to tissue-healing and regeneration range from experimental techniques in preclinical testing to techniques currently in use [8], with new techniques utilizing growth factors and cell and gene therapies offering the potential to enhance the rate and quality of healing of ligaments of the knee [10]. However, additional cell seeding did not enhance osteointegration of a silk fiber–based ACL scaffold, and a longer observation period is necessary to determine if a true ligament-bone enthesis will be formed with such a scaffold [11].

Clinical outcomes are influenced by ligament quality and specific injury patterns. Patients with poor ligament quality have inferior clinical outcomes after arthroscopic all-inside anterior talofibular ligament repair, associated with lower scores and fewer patients exceeding the minimal clinically important difference threshold in sports-related activities [21]. Anterolateral ligament injuries occurred in the majority of ACL-injured knees but had limited intrinsic healing potential, with only 30.3% of anterolateral ligament injuries healed by 12 months after ACL reconstruction [18]. Better functional and clinical outcomes have been achieved with reconstruction rather than repair for multiligament-injured knees [19]. Treatment of acute tears of the medial ligaments, with or without an associated tear of the anterior cruciate ligament, provides good long-term results [22]. There is renewed interest and focus for primary ACL repair that may yet prove the new frontier in ligament repair [9], and a growing body of evidence supports the use of PRP in selected indications for knee disorders [20]. The palmar portion of the scapholunate ligament plays a stabilizing role and should be considered for surgical repair [33]. A variety of definitions of failure are used among studies published in the orthopaedic literature regarding anterior cruciate ligament reconstruction, and a clearer definition of instability would facilitate the development and assessment of interventions for instability [36, 56].

How It Works

Intrinsic Healing and Biological Response

The human anterior cruciate ligament (ACL) undergoes four distinct histological phases following rupture: inflammation, epiligamentous regeneration, proliferation, and remodeling [30]. Despite this biological cascade, the ACL possesses limited intrinsic healing capability due to a lack of localized hematoma and low reparative cell supply [7]. In contrast, extra-articular ligaments such as the medial collateral ligament (MCL) heal spontaneously, although this process results in poor mechanical properties [7]. Biomechanical testing has not demonstrated functional differences in MCL healing despite the increased biological response to hemorrhage [2]. In the rabbit model, injury triggers an antifibrotic, catabolic response in the ACL, a mechanism possibly intended to prevent fibrosis and diminish the risk for loss of joint motion [23]. The anterolateral ligament also exhibits limited intrinsic healing potential, with only 30.3% of injuries healing by 12 months after ACL reconstruction [18]. At the cellular level, myofibroblasts may be involved in crimp formation and should be viewed as an integral part of normal tendon and ligament tissue [37]. Additionally, cells within a tendon graft contribute significantly to collagen synthesis and play a role in healing, although they are not essential [34].

Graft Healing and Remodeling

Early functional outcomes diverge based on tissue type: ligament function after repair depends on the cellular population of the repair, whereas early graft function depends on the maintenance of organized collagen [4]. Despite ongoing remodelling, an ACL graft retains a deficit in tensile strength and stiffness compared to the original ligament [12]. This persistent deficit in tensile strength and stiffness may explain high failure rates in the first year after ACL reconstruction [12]. Understanding spatial and time-dependent changes in graft healing is critical for developing strategies to achieve full restoration of function and mechanical strength of intact cruciate ligaments [5]. Recent improvements in ACL reconstruction have focused on strategies to improve graft placements and methodologies to enhance graft healing [13]. Concurrently, efforts to advance clinical success have targeted enhancing and optimizing the biologic environment of the graft-bone interface to promote healing rate and strength [16]. Nonabsorbable suture augmentation protects the ligament from early failure, but stress shielding may negatively impact the final strength and composition of the reconstructed ligament [17]. Histologically, additional cell seeding did not enhance osteointegration of a silk fiber-based ACL scaffold [11].

Therapeutic Interventions and Regeneration

The application of a basic fibroblast growth factor-impregnated pellet seems to enhance the healing potential of the partially lacerated ACL [14]. The addition of a collagen-platelet composite to a suture repair enhanced the structural properties of the ACL [27]. This improvement in structural properties was associated with increased cellularity within the healing ligament [27]. Clinically applicable solutions to prevent tendon adhesions remain elusive despite progress in understanding the mechanism of tendon healing and adhesions [26]. Genetic alterations in key proteoglycans and glycoproteins are identified as potential drug targets for disrupting pathological mechanisms leading to ligamentopathy [25]. There is renewed interest and focus for primary ACL repair that may yet prove the new frontier in ligament repair [9].

What the Evidence Shows

Intrinsic Healing Potential and Biology

The anterolateral ligament demonstrates limited intrinsic healing potential, with only 30.3% healing by 12 months after ACLR [18]. Understanding spatial and time-dependent changes in graft healing is of significant importance to develop strategies for improved treatment options in cruciate ligament surgery [5]. Key biological differences exist in the development and maintenance of ACL tissue after repair or reconstruction, with early ligament function dependent on the cellular population of the repair and early graft function dependent on the maintenance of organized collagen [4]. Despite remodelling, the graft retains a deficit in tensile strength and stiffness compared to the original ligament, which may explain high failure rates in the first year [12]. Cells in the graft contribute significantly to collagen synthesis and have a role in healing, although they are not essential [34]. Preserving small amounts of muscle on tendon grafts is feasible for improving the biological success of ACL reconstruction in humans [35]. Clinically applicable solutions to prevent adhesions remain elusive despite progress in understanding the mechanism of tendon healing and adhesions [26]. Genetic alterations and knockdown approaches identify key proteoglycans and glycoproteins as potential drug targets for disrupting pathological mechanisms leading to tendinopathy, ligamentopathy, and enthesopathy [25].

Hemorrhage and Inflammation

Biomechanical testing did not demonstrate functional differences associated with the increased healing response from bleeding at the ligament injury site [2]. The primary use of glucocorticoids did not exert any obvious deleterious side effects on the treated tendon but instead enhanced the regenerative effects of platelet-rich plasma in early inflammatory tendinopathy [46].

Biologics and Tissue Engineering

The application of a bFGF-impregnated pellet seems to enhance the healing potential of the partially lacerated ACL [14]. Injected mesenchymal stromal cells can accelerate the healing of partially torn ACLs [47]. The addition of a collagen-platelet composite to a suture repair enhanced the structural properties of the ACL, and the improvement was associated with increased cellularity within the healing ligament [27]. Recent efforts at advancing the clinical success of ACL reconstruction have focused on strategies to enhance and optimize the biologic environment of the graft-bone interface to promote and potentially improve the healing rate and strength of the reconstruction [16]. PRP alone and BMAC and PRP combination showed limited enhancing effect in clinical function, graft maturation and tendon–bone interfacial healing compared with control (no additional treatment) [43]. Future studies should provide more standardisation to investigate the benefits of biological augmentation in ACL surgery [32]. Histologically, additional cell seeding did not enhance osteointegration of a novel silk fiber–based ACL scaffold, and a longer observation period is necessary to see if a true ligament-bone enthesis will be formed [11]. The symposium discussed biologic approaches to tissue-healing and regeneration, ranging from experimental techniques in preclinical testing to techniques currently in use, providing a basis for future studies in tissue engineering [8]. Understanding of these topics could lead to more efficacious therapies to treat ligament and tendon injuries [1]. Future directions include implementing randomized controlled trials and developing multifunctional biomaterials to improve patient outcomes [48].

Surgical Techniques and Augmentation

Recent improvements in anterior cruciate ligament reconstruction have focused on strategies to improve graft placements and methodologies to enhance graft healing, with new biologic engineering strategies evolving for clinical application [13]. Although nonabsorbable suture augmentation protects the ligament from early failure, stress shielding may negatively impact the final strength and composition of the reconstructed ligament [17]. Published data on the use of suture augmentation to augment repairs of the ulnar collateral ligament, thumb collateral ligament, anterior cruciate ligament, Achilles' tendon, and deltoid ligament repair demonstrate improved time-zero biomechanical and promising short- to mid-term clinical outcomes [53]. More high-quality large randomized clinical trials with longer follow-up comparing ACL suture repair and reconstruction are needed [28]. The best treatment does not exist, but better functional and clinical outcomes have been achieved with reconstruction rather than repair for multiligament-injured knees [19]. Nonoperative and operative treatments of medial collateral ligament injuries lead to equally good results [41]. Nonoperative treatment for MCL injuries combined with ACL reconstruction is an effective treatment and provides similar clinical outcomes to those of isolated ACL reconstruction without an MCL injury [51]. This previously described treatment of acute tears of the medial ligaments, with or without an associated tear of the anterior cruciate ligament, provides good long-term results and is still recommended [22]. Although this is a short-term follow-up study involving a small number of cases, the authors considered their procedure to be an effective method of surgically restoring the function of the medial collateral ligament [42]. Acute repairs have predictably good outcomes while the treatment of chronic injuries is less predictable, but generally reliable, for most patients [50]. Minimally invasive techniques and ligament-preserving decompression may help mitigate iatrogenic alterations on adjacent segment degeneration after lumbar fusion surgery, though further research is necessary to fully elucidate these mechanisms [15].

Outcomes and Failure

Patients with poor ligament quality have inferior clinical outcomes, particularly in terms of sports-related activities, as reflected by both lower scores and fewer patients exceeding the minimal clinically important difference threshold [21]. The review identifies a clear deficiency in the literature pertaining to consistent, meaningful postoperative return to sport timeline following lateral ankle ligament repair [24]. Objectively, lateral tenodesis appears to improve more effectively restoration of laxity in patients suffering from chronic ankle instability up to 15 years from surgery [40]. Knowledge of the anterolateral ligament's tensile strengths may help to better understand its function and with graft choices for reconstruction procedures [31]. In this study, we found that a variety of definitions of failure are used among studies published in the orthopaedic literature [36]. This review article provides a comprehensive analysis of the potential causes of failure after anterior cruciate ligament reconstruction, including graft failure, loss of motion, extensor mechanism dysfunction, osteoarthritis, and infection [57]. The review demonstrates equivalent clinical results with the use of autografts or allografts in posterior cruciate, collateral and multi-ligament knee reconstruction [58]. Our study indicated strong evidence in support of a significant effect of ACL injury prevention programs [49].

Practical Considerations

Biological Environment and Healing Potential

The anterior cruciate ligament (ACL) possesses a limited capacity for intrinsic healing, a constraint driven by the absence of a localized hematoma and a low supply of reparative cells [7]. Following rupture, the human ACL progresses through four distinct histological phases: inflammation, epiligamentous regeneration, proliferation, and remodeling [30]. Although hemorrhage triggers an increased biological response in the medial collateral ligament (MCL), biomechanical testing has not demonstrated functional differences in MCL healing [2]. Ligaments with rich innervation are proposed to provide proprioceptive information [39]. The retained deficit in graft tensile strength and stiffness may explain the high failure rates observed during the first year post-reconstruction [12].

Surgical Strategies and Augmentation

Primary ACL repair remains a controversial procedure, characterized by limited medium- and long-term outcomes [45]. Caution is required when performing primary ACL repair in athletes and younger patients due to higher failure rates [45]. Nonabsorbable suture augmentation protects the ligament from early failure [17]; however, stress shielding from this augmentation may negatively impact the final strength and composition of the reconstructed ligament [17]. The routine use of suture tape augmentation for primary ACL reconstruction is not justified based on current evidence [54]. The available data for suture tape augmentation lacks robustness and sufficient sample size to support firm conclusions [54]. Regarding silk fiber-based scaffolds, a longer observation period is necessary to determine if a true ligament-bone enthesis will be formed [11].

Rehabilitation and Clinical Outcomes

Treatment of acute tears of the medial ligaments, with or without an associated ACL tear, provides good long-term results and is still recommended [22]. A delayed ACL reconstruction after 6 weeks of MCL rehabilitation is recommended to allow for potential MCL healing [52]. There is a clear deficiency in the literature pertaining to consistent, meaningful postoperative return to sport timelines following lateral ankle ligament repair [24].

Emerging Therapies and Research

New biologic engineering strategies are evolving for clinical application in ACL reconstruction [13]. Recent efforts to advance the clinical success of ACL reconstruction have focused on strategies to enhance and optimize the biologic environment of the graft-bone interface [16]. Optimizing this biologic environment aims to promote and potentially improve the healing rate and strength of the reconstruction [16]. Understanding spatial and time-dependent changes in graft healing is of significant importance to develop strategies for improved treatment options in cruciate ligament surgery [5].

Key Evidence

  • [L5] Understanding of these topics could lead to more efficacious therapies to treat ligament and tendon injuries. [1] (10.1002/jor.24475)
  • [L5] This study suggests there is an increased healing response with bleeding at the ligament injury site, evidenced by increased macrophage counts and collagen gene expression, though biomechanical testing did not demonstrate functional differences. [2] (10.1177/03635465030310050501)
  • [L5] Early controlled motion of stable or surgically stabilized joints appears to improve ligament scar behavior, but no treatment identified to date stimulates true ligament regeneration. [3] (10.5435/00124635-199603000-00002)
  • [L5] These findings suggest there may be key biological differences in development and maintenance of ACL tissue after repair or reconstruction, with early ligament function dependent on cellular population of the repair but early graft function dependent on the maintenance of organized collagen. [4] (10.1177/2325967113512457)
  • [L5] The understanding of the spatial and time-dependent changes as well as the differences between the different models of graft healing are of significant importance to develop strategies of improved treatment options in cruciate ligament surgery, so that full restoration of function and mechanical strength of the intact cruciate ligaments will be achieved. [5] (10.1007/s00167-008-0560-8)
  • [L5] This study indicates that the radioscapholunate ligament has a vascular supply that may be sufficient for healing by known methods. [6] (10.1016/0363-5023(90)90108-4)
  • [L5] The paper outlines that the ACL has limited capability to heal due to a lack of localized hematoma and low reparative cell supply, whereas extra-articular ligaments like the MCL heal spontaneously but with poor mechanical properties. [7] (10.1186/1758-2555-2-12)
  • [L5] The symposium discussed biologic approaches to tissue-healing and regeneration, ranging from experimental techniques in preclinical testing to techniques currently in use, providing a basis for future studies in tissue engineering. [8] (10.2106/jbjs.k.01505)
  • [L5] Further work is clearly needed but there is renewed interest and focus for primary ACL repair that may yet prove the new frontier in ligament repair. [9] (10.1186/s40634-018-0136-6)
  • [L5] New techniques utilizing growth factors and cell and gene therapies may offer the potential to enhance the rate and quality of healing of ligaments of the knee. [10] (10.5435/00124635-200011000-00004)
  • [L5] Histologically, additional cell seeding did not enhance osteointegration, and a longer observation period is necessary to see if a true ligament-bone enthesis will be formed. [11] (10.1177/0363546518818792)
  • [L5] It notes that despite remodelling, the graft retains a deficit in tensile strength and stiffness compared to the original ligament, which may explain high failure rates in the first year. [12] (10.1136/jisakos-2015-000041)
  • [L5] Recent improvements in anterior cruciate ligament reconstruction have focused on strategies to improve graft placements and methodologies to enhance graft healing, with new biologic engineering strategies evolving for clinical application. [13] (10.1177/0363546507311690)
  • [L5] The application of a bFGF-impregnated pellet seems to enhance the healing potential of the partially lacerated ACL. [14] (10.1007/s001670050049)
  • [L1] Minimally invasive techniques and ligament-preserving decompression may help mitigate these effects, though further research is necessary to fully elucidate these mechanisms. [15] (10.1186/s13018-025-05561-1)
  • [L5] Recent efforts at advancing the clinical success of ACL reconstruction have focused on strategies to enhance and optimize the biologic environment of the graft-bone interface to promote and potentially improve the healing rate and strength of the reconstruction. [16] (10.1016/j.csm.2012.08.010)
  • [L5] Although nonabsorbable suture augmentation protects the ligament from early failure, stress shielding may negatively impact the final strength and composition of the reconstructed ligament. [17] (10.1016/j.jhsa.2021.09.014)
  • [L4] ALL injuries occurred in the majority of ACL-injured knees and had limited intrinsic healing potential, with only 30.3% healing by 12 months after ACLR. [18] (10.1177/03635465211013015)
  • [L2] The review suggests that the best treatment does not exist, but better functional and clinical outcomes have been achieved with reconstruction rather than repair. [19] (10.1016/j.injury.2019.01.052)
  • [L5] There is a growing body of evidence to support the use of PRP in selected indications for knee disorders. [20] (10.1302/2058-5241.2.160004)
  • [L3] However, patients with poor ligament quality have inferior clinical outcomes, particularly in terms of sports-related activities, as reflected by both lower scores and fewer patients exceeding the minimal clinically important difference threshold. [21] (10.1016/j.arthro.2025.04.032)
  • [L4] This previously described treatment of acute tears of the medial ligaments, with or without an associated tear of the anterior cruciate ligament, provides good long-term results and is still recommended. [22] (10.2106/00004623-199506000-00018)
  • [L5] The results suggest that injury leads to an antifibrotic, catabolic response in the rabbit anterior cruciate ligament, possibly to prevent fibrosis and diminish the risk for loss of joint motion. [23] (10.1177/0363546508316283)
  • [L4] The review identifies a clear deficiency in the literature pertaining to consistent, meaningful postoperative return to sport timeline following lateral ankle ligament repair. [24] (10.1136/jisakos-2016-000064)
  • [L4] This review summarizes genetic alterations and knockdown approaches to assess the role of key proteoglycans and glycoproteins in the structural development, function, and repair of tendon, ligament, and enthesis, identifying these genes as potential drug targets for disrupting pathological mechanisms leading to tendinopathy, ligamentopathy, and enthesopathy. [25] (10.1155/2013/154812)
  • [L5] Clinically applicable solutions to prevent adhesions remain elusive despite progress in understanding the mechanism of tendon healing and adhesions. [26] (10.1016/j.jhsa.2017.06.013)
  • [L5] The addition of a CPC to a suture repair enhanced the structural properties of the ACL, and the improvement was associated with increased cellularity within the healing ligament. [27] (10.1177/0363546509339915)
  • [L1] More high-quality large randomized clinical trials with longer follow-up comparing ACL suture repair and reconstruction are needed. [28] (10.1177/0363546520904690)
  • [L4] After rupture, the human anterior cruciate ligament undergoes four histological phases consisting of inflammation, epiligamentous regeneration, proliferation, and remodeling. [30] (10.2106/00004623-200010000-00004)
  • [L5] Knowledge of the anterolateral ligament's tensile strengths may help to better understand its function and with graft choices for reconstruction procedures. [31] (10.1186/s40634-015-0023-3)
  • [L1] Future studies should provide more standardisation to investigate the benefits of biological augmentation in ACL surgery. [32] (10.1002/ksa.12127)
  • [L5] These results appear to agree with other reports about the stabilizing role of the palmar portion of the scapholunate ligament and suggest that the palmar portion of the ligament should be considered for surgical repair. [33] (10.1016/j.clinbiomech.2011.04.009)
  • [L5] Cells in the graft contributed significantly to collagen synthesis and do have a role in healing, although they are not essential. [34] (10.1177/1753193412471103)
  • [L5] Preserving small amounts of muscle on tendon grafts is feasible for improving the biological success of ACL reconstruction in humans. [35] (10.1007/s00167-012-2181-5)
  • [L4] In this study, we found that a variety of definitions of failure are used among studies published in the orthopaedic literature. [36] (10.1016/j.asmr.2023.100801)
  • [L5] Myofibroblasts might be involved in crimp formation and should be viewed as an integral part of normal tendon and ligament tissue. [37] (10.1007/s00167-011-1644-4)
  • [L4] The variations found imply a functional difference correlating to the histological variations, where ligaments with rich innervation are proposed to provide proprioceptive information. [39] (10.1016/j.orthres.2005.01.011)
  • [L3] Objectively, lateral tenodesis appears to improve more effectively restoration of laxity. [40] (10.1007/s00167-018-5244-4)
  • [L1] Nonoperative and operative treatments of medial collateral ligament injuries lead to equally good results. [41] (10.1177/0363546505284889)
  • [L4] Although this is a short-term follow-up study involving a small number of cases, the authors considered their procedure to be an effective method of surgically restoring the function of the medial collateral ligament. [42] (10.1177/0363546504273487)
  • [L2] PRP alone and BMAC and PRP combination showed limited enhancing effect in clinical function, graft maturation and tendon–bone interfacial healing compared with control (no additional treatment). [43] (10.1186/s13018-023-04512-y)
  • [L4] The procedure remains controversial with limited medium- and long-term outcomes, requiring caution in athletes and younger patients due to higher failure rates. [45] (10.5435/jaaos-d-20-00077)
  • [L5] The primary use of glucocorticoids did not exert any obvious deleterious side effects on the treated tendon but instead enhanced the regenerative effects of platelet-rich plasma in early inflammatory tendinopathy. [46] (10.1177/03635465211037354)
  • [L5] Injected mesenchymal stromal cells can accelerate the healing of partially torn ACLs. [47] (10.1016/j.arthro.2007.01.013)
  • [L5] Future directions include implementing randomized controlled trials and developing multifunctional biomaterials to improve patient outcomes. [48] (10.1186/s13018-025-06436-1)
  • [L1] Our study indicated strong evidence in support of a significant effect of ACL injury prevention programs. [49] (10.2106/jbjs.k.00467)
  • [L5] Acute repairs have predictably good outcomes while the treatment of chronic injuries is less predictable, but generally reliable, for most patients. [50] (10.1016/j.csm.2014.09.004)
  • [L3] Nonoperative treatment for MCL injuries combined ACL reconstruction is an effective treatment and provides similar clinical outcomes to those of isolated ACL reconstruction without an MCL injury. [51] (10.1016/j.jisako.2025.100515)
  • [L5] The authors recommend a delayed ACL reconstruction after 6 weeks of MCL rehabilitation to allow for potential MCL healing. [52] (10.1016/j.csm.2016.08.005)
  • [L5] Published data on the use of suture augmentation to augment repairs of the ulnar collateral ligament, thumb collateral ligament, anterior cruciate ligament, Achilles' tendon, and deltoid ligament repair demonstrate improved time-zero biomechanical and promising short- to mid-term clinical outcomes. [53] (10.1016/j.arthro.2023.01.012)
  • [L5] The routine use of suture tape augmentation for primary anterior cruciate ligament reconstruction surgery is not justified based on the current evidence, as the available data lacks robustness and sufficient sample size to support firm conclusions. [54] (10.1016/j.arthro.2024.02.022)
  • [L4] A clearer definition of instability would facilitate the development and assessment of interventions for instability. [56] (10.1177/1758998317698099)
  • [L4] This review article provides a comprehensive analysis of the potential causes of failure after anterior cruciate ligament reconstruction, including graft failure, loss of motion, extensor mechanism dysfunction, osteoarthritis, and infection. [57] (10.1016/j.csm.2012.08.015)
  • [L4] The review demonstrates equivalent clinical results with the use of autografts or allografts. [58] (10.1007/s00167-019-05426-1)

See Also

  • Osteoarthritis

References

[1] Tendon and Ligament Healing and Current Approaches to Tendon and Ligament Regeneration. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24475

[2] Effect of Hemorrhage on Medial Collateral Ligament Healing in a Mouse Model. The American Journal of Sports Medicine. 2003. DOI: 10.1177/03635465030310050501

[3] Ligament Healing: Current Knowledge and Clinical Applications. Journal of the American Academy of Orthopaedic Surgeons. 1996. DOI: 10.5435/00124635-199603000-00002

[4] Histological Predictors of Maximum Failure Loads Differ Between the Healing ACL and ACL Grafts After 6 and 12 Months In Vivo. Orthopaedic Journal of Sports Medicine. 2013. DOI: 10.1177/2325967113512457

[5] Graft remodeling and ligamentization after cruciate ligament reconstruction. Knee Surgery, Sports Traumatology, Arthroscopy. 2008. DOI: 10.1007/s00167-008-0560-8

[6] Microvascular anatomy of the radioscapholunate ligament of the wrist. The Journal of Hand Surgery. 1990. DOI: 10.1016/0363-5023(90)90108-4

[7] Functional tissue engineering of ligament healing. BMC Sports Science, Medicine and Rehabilitation. 2010. DOI: 10.1186/1758-2555-2-12

[8] 2011 AOA Symposium: Tissue Engineering and Tissue Regeneration. The Journal of Bone and Joint Surgery-American Volume. 2013. DOI: 10.2106/jbjs.k.01505

[9] Anterior cruciate ligament repair – past, present and future. Journal of Experimental Orthopaedics. 2018. DOI: 10.1186/s40634-018-0136-6

[10] Healing and Repair of Ligament Injuries in the Knee. Journal of the American Academy of Orthopaedic Surgeons. 2000. DOI: 10.5435/00124635-200011000-00004

[11] Osteointegration of a Novel Silk Fiber–Based ACL Scaffold by Formation of a Ligament-Bone Interface. The American Journal of Sports Medicine. 2019. DOI: 10.1177/0363546518818792

[12] Review of Clancy's article on anterior and posterior cruciate ligament reconstruction in rhesus monkeys. Journal of ISAKOS. 2016. DOI: 10.1136/jisakos-2015-000041

[13] Strategies to Improve Anterior Cruciate Ligament Healing and Graft Placement. The American Journal of Sports Medicine. 2008. DOI: 10.1177/0363546507311690

[14] Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament. Knee Surgery, Sports Traumatology, Arthroscopy. 1997. DOI: 10.1007/s001670050049

[15] Impact of iatrogenic alterations on adjacent segment degeneration after lumbar fusion surgery: a systematic review. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-05561-1

[16] ACL Graft Healing and Biologics. Clinics in Sports Medicine. 2013. DOI: 10.1016/j.csm.2012.08.010

[17] Stress Shielding of Ligaments Using Nonabsorbable Suture Augmentation May Influence the Biology of Ligament Healing. The Journal of Hand Surgery. 2022. DOI: 10.1016/j.jhsa.2021.09.014

[18] The Anterolateral Ligament Has Limited Intrinsic Healing Potential: A Serial, 3-Dimensional–Magnetic Resonance Imaging Study of Anterior Cruciate Ligament–Injured Knees From the SANTI Study Group. The American Journal of Sports Medicine. 2021. DOI: 10.1177/03635465211013015

[19] Major concern in the multiligament-injured knee treatment: A systematic review. Injury. 2019. DOI: 10.1016/j.injury.2019.01.052

[20] Platelet-rich plasma (PRP) for knee disorders. EFORT Open Reviews. 2017. DOI: 10.1302/2058-5241.2.160004

[21] Ligament Quality Predicts Recurrence and Functional Outcomes After Arthroscopic All‐Inside Anterior Talofibular Ligament Repair. Arthroscopy. 2025. DOI: 10.1016/j.arthro.2025.04.032

[22] The importance of the posterior oblique ligament in repairs of acute tears of the medial ligaments in knees with and without an associated rupture of the anterior cruciate ligament. Results of long-term follow-up.. The Journal of Bone & Joint Surgery. 1995. DOI: 10.2106/00004623-199506000-00018

[23] Injury-Induced Changes in mRNA Levels Differ Widely between Anterior Cruciate Ligament and Medial Collateral Ligament. The American Journal of Sports Medicine. 2008. DOI: 10.1177/0363546508316283

[24] Return to sport following lateral ankle ligament repair is under-reported: a systematic review. Journal of ISAKOS. 2017. DOI: 10.1136/jisakos-2016-000064

[25] Defects in Tendon, Ligament, and Enthesis in Response to Genetic Alterations in Key Proteoglycans and Glycoproteins: A Review. Arthritis. 2013. DOI: 10.1155/2013/154812

[26] Molecular Biology of Flexor Tendon Healing in Relation to Reduction of Tendon Adhesions. The Journal of Hand Surgery. 2017. DOI: 10.1016/j.jhsa.2017.06.013

[27] Collagen-Platelet Composite Enhances Biomechanical and Histologic Healing of the Porcine Anterior Cruciate Ligament. The American Journal of Sports Medicine. 2009. DOI: 10.1177/0363546509339915

[28] Efficacy of Nonaugmented, Static Augmented, and Dynamic Augmented Suture Repair of the Ruptured Anterior Cruciate Ligament: A Systematic Review of the Literature. The American Journal of Sports Medicine. 2020. DOI: 10.1177/0363546520904690

[30] Histological Changes in the Human Anterior Cruciate Ligament After Rupture. The Journal of Bone and Joint Surgery-American Volume*. 2000. DOI: 10.2106/00004623-200010000-00004

[31] Mechanical tensile properties of the anterolateral ligament. Journal of Experimental Orthopaedics. 2015. DOI: 10.1186/s40634-015-0023-3

[32] Platelet‐rich plasma augmentation in anterior cruciate ligament reconstruction: Evidence is still too scattered. A scoping review of randomised controlled trials. Knee Surgery, Sports Traumatology, Arthroscopy. 2024. DOI: 10.1002/ksa.12127

[33] Biomechanical properties of the scapholunate ligament and the importance of its portions in the capitate intrusion injury. Clinical Biomechanics. 2011. DOI: 10.1016/j.clinbiomech.2011.04.009

[34] The cellular biology of tendon grafting. Journal of Hand Surgery (European Volume). 2013. DOI: 10.1177/1753193412471103

[35] Effect of muscle preserved on tendon graft on intra‐articular healing in anterior cruciate ligament reconstruction. Knee Surgery, Sports Traumatology, Arthroscopy. 2012. DOI: 10.1007/s00167-012-2181-5

[36] Various Definitions of Failure Are Used in Studies of Patients Who Underwent Anterior Cruciate Ligament Reconstruction. Arthroscopy, Sports Medicine, and Rehabilitation. 2023. DOI: 10.1016/j.asmr.2023.100801

[37] Crimp frequency is strongly correlated to myofibroblast density in the human anterior cruciate ligament and its autologous tendon grafts. Knee Surgery, Sports Traumatology, Arthroscopy. 2011. DOI: 10.1007/s00167-011-1644-4

[39] Differences in the presence of mechanoreceptors and nerve structures between wrist ligaments may imply differential roles in wrist stabilization. Journal of Orthopaedic Research. 2005. DOI: 10.1016/j.orthres.2005.01.011

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