General, Rodilla, Traumatología deportiva, Investigación y tecnología

Biologic Approaches for the Treatment of Partial Tears of the Anterior Cruciate Ligament A Current Concepts Review

Biologic Approaches for the Treatment of Partial Tears of the Anterior Cruciate Ligament

A Current Concepts Review

, MD*, , MD, , MD, , MD, ,MD, , MD, PhD, §

*Sanatorio Garay, Santa Fe, Argentina.
†The Steadman Philippon Research Institute, Vail, Colorado, USA.
‡University of Colorado, Boulder, Colorado, USA.
§The Steadman Clinic, Vail, CO, USA.

Orthopaedic Journal of Sports Medicine. January 1, 2017


Anterior cruciate ligament reconstruction (ACLR) has been established as the gold standard for treatment of complete ruptures of the anterior cruciate ligament (ACL) in active, symptomatic individuals. In contrast, treatment of partial tears of the ACL remains controversial. Biologically augmented ACL-repair techniques are expanding in an attempt to regenerate and improve healing and outcomes of both the native ACL and the reconstructed graft tissue.

To review the biologic treatment options for partial tears of the ACL.


A literature review was performed that included searches of PubMed, Medline, and Cochrane databases using the following keywords: partial tear of the ACL, ACL repair, bone marrow concentrate, growth factors/healing enhancement, platelet-rich plasma (PRP), stem cell therapy.

The use of novel biologic ACL repair techniques, including growth factors, PRP, stem cells, and bioscaffolds, have been reported to result in promising preclinical and short-term clinical outcomes.

The potential benefits of these biological augmentation approaches for partial ACL tears are improved healing, better proprioception, and a faster return to sport and activities of daily living when compared with standard reconstruction procedures. However, long-term studies with larger cohorts of patients and with technique validation are necessary to assess the real effect of these approaches.

The anterior cruciate ligament (ACL) is one of the most studied structures of the human musculoskeletal system, being the subject of many anatomic and biomechanical studies. While treatment options for complete ruptures of the ACL are well studied, partial ACL tears remain more nebulous in their postinjury treatment course. Partial ACL tears were first described almost 5 decades ago.91 However, since the initial description, there remains no consensus on the classification for these injuries, and the optimal treatment continues to be a subject of considerable debate.71 Complete tears of the ACL can result in immediate anteroposterior and rotational knee instability. Anterior cruciate ligament reconstruction (ACLR) has been reported to achieve a near-native biomechanical function in symptomatic patients.34 However, when the ACL is partially torn, the natural evolution of these lesions is poorly understood and thus, the evidence regarding treatment options is limited.69

Unlike other ligaments of the knee, such as the posterior cruciate ligament (PCL) and medial collateral ligament (MCL), the ACL possesses limited intrinsic capacity for spontaneous healing after an injury.8389 Early reports of direct suture repair of the ACL culminated in failure in 40% to 100% of cases.47 In part, the poor healing capacity of the ACL has been speculated to be a consequence of its intra-articular location and a thin synovial membrane. Generally, ligamentous injuries trigger the release of proinflammatory cytokines that initiate formation of a fibrin-platelet clot scaffold that is rapidly replaced by granulation tissue, and weeks later by immature, parallel collagen fibers.83However, several studies have demonstrated the inhibitory properties of the intra-articular synovial fluid of the knee on fibrin-platelet clot formation and ACL fibroblast migration in patients suffering ACL injury.47,68,83 Thus, the capacity for spontaneous repair and remodeling after ACL injury is relatively poor, thereby requiring surgical reconstruction or augmentation to recover stability in many cases.89

This clearly induces a dilemma in the treatment of partial ACL injuries. Despite being the historical standard of care for complete ACL disruptions, ACLR procedures have been reported to potentially result in diminished proprioception, postoperative muscular weakness, inability to fully restore normal kinematics, donor site morbidity, and possible premature osteoarthritis (OA).8,30,37,44 Biau et al10reported in a meta-analysis that only 40% of patients who had an ACLR achieved full recovery independent of the surgical technique, and Kartus et al37 reported that 65% of patients had anterior knee pain and disturbance of anterior sensitivity caused by intraoperative injury to the infrapatellar nerve(s) after ACLR with patellar tendon autograft. These findings are of particular concern in combination with the findings of Barenius et al,8 which showed that 57% and 18% of patients will develop osteoarthritis at 14-year follow-up in the ACL reconstructed knee and in the contralateral knee, respectively. Zhou et al93 evaluated knee proprioception with a passive reproduction test and isokinetic strength in 36 patients who had their ACL reconstructed with semitendinosus/gracilis grafts (reconstructed group: 6 months after surgery) and 13 healthy adults without any knee injury. They reported a significant difference in proprioception between the reconstructed and control groups and concluded that impaired knee proprioception is observed 6 months after ACLR.

Many studies have shown significantly greater translational and rotational laxity of the reconstructed knees relative to the contralateral uninjured sides, regardless of the graft type.9,78 Additionally, high-demand activities among patients with ACLR reportedly lead to increased tibial rotation and impaired neuromuscular control that potentially results in an increase of cartilage load and thus higher risk of reinjury.27 Shah et al,70 in a case series of 49 National Football League (NFL) athletes who had undergone primary ACLR, concluded that the return to play after ACLR in NFL football players was lower than previously perceived; only 63% of NFL athletes returned to NFL game play at an average of 10.8 months after surgery. In contrast, a higher rate of return to play was found in recreational athletes; Ardern et al6 in a systematic review found that an average of 82% of athletes returned to sports in this group.

Thus, due to the evolving understanding of tissue engineering and regenerative medicine, there has been a recent interest in the development of new biological treatment techniques to address partial injuries of intra-articular structures, such as the ACL. The use of biologic approaches, including different growth factors, platelet-rich plasma (PRP), stem cells, biological scaffolds, and augmented ACL primary repair, has been the focus of current research in ACL accelerated repair and healing. These alternatives to the current surgical reconstruction techniques have the potential to preserve the native insertion site of the remaining fibers and therefore its proprioceptive function, which may in turn lead to biomechanics that are more natural.42,53 As biologic approaches appear to be one possible future treatment for a subset of orthopaedic injuries, the purpose of this article was to review the current biologic treatments of partial tears of the ACL.

The first ACL repair was reported in 1895.67 In Europe, in 1927, Wittek86 described and illustrated the different types of tears of the ACL. Later, in 1935, Wittek87 published a technique to surgically treat ACL tears using a distally based strip of extensor retinaculum and the medial border of the patellar tendon, brought into the joint through a tibial tunnel and secured against the anterior-superior aspect of the PCL with sutures. In the 1970s, Feagin and Curl24 began to further evaluate the possibility of ACL repair in isolated and acute tears utilizing a polyglycolic acid suture woven through the tibial stump and passed up through bone tunnels in the femur. Postoperatively, patients were immobilized for 6 weeks at 30° of flexion, and then allowed to begin a motion program with progressive return to activity. The authors reported that 25 of these 30 active patients had good results at a minimum of 2 years’ follow-up. However, at 5 years’ follow-up the results showed that 71% of patients had pain and 94% had knee instability.23 These findings led to the conclusion that primary ACL repair had good outcomes in only one-third of patients treated in this cohort. However, the patients who initially had good outcomes at 5 years (one third) preserved the good outcomes at 30 years postoperatively.79

This seemed to suggest that there was a small subset of patients that could progress well after ACL repair if indicated appropriately. It should be noted that long-term clinical studies that reported ACL repair as ineffective were based on these original “failed” cohorts from the 1970s and 1980s and thus may not accurately reflect modern surgical acumen.80 ACL repair has been abandoned in favor of ACLR largely because of the unpredictable results of the procedure. Historically, it was suggested that suture techniques alone may be useful for ACL injuries in which the ends of the torn tissue can be reapproximated under compression. Not surprisingly, a lower-demand subset of patients experienced better results than high-demand patients when this technique was utilized.65 Long-term follow-up studies of primary repair reported poor results in nearly 30% of the patients,76 high rates of additional surgery needed (64%),79 and revision to ACLR for instability (13%-24%). In addition, objective laxity >5 mm by KT-1000 assessment was reported in 21% of these patients.76 Modern surgical options and advancements in biological understanding have led researchers to reconsider the repair of ACL ruptures. However, longer follow-up with larger cohorts are needed to assess the real efficacy of this approach.

Partial ACL tears (Figure 1) must be treated early enough to prevent a large number of secondary instability-derived events, particularly meniscal damage, accelerated cartilage degenerative changes and functional disability.71 Preserving native ACL remnant fibers, when partially torn, may provide several theoretical advantages over reconstruction, including preservation of the natural anatomy, physiology, proprioception, and intrinsic cell populations, as well as some of the complex biomechanical properties of the knee.65 There are several basic research studies and surgical techniques published on preservation of the nondamaged fibers in cases of partial ACL tears. However, there are few published studies on the short- and medium-term clinical outcomes.71


Figure 1. Magnetic resonance imaging (sagittal view) demonstrating a partial anterior cruciate ligament (ACL) tear. On the upper-right corner, the corresponding arthroscopic view (through the anterolateral portal) shows the posterolateral bundle tear of the ACL in a left knee.

When considering partial tears of the ACL, understanding the anatomy and properties of this ligament is vital. The ACL is an intra-articular and extrasynovial ligament with a multifilament structure consisting of 2 separate bundles that maintain different tensions according to the degree of flexion of the knee joint.2,38 These distinct anteromedial (AM) and posterolateral (PL) bundles act in concert during both flexion and extension moments of the knee with the AM bundle tight in flexion and the PL bundle tight in extension.3,4,81,92 These bundles attach proximally at the posterior aspect of the medial wall of the lateral femoral condyle posterior to the lateral intercondylar ridge, and are similar in size at the femoral insertion94 (Figure 2). The length of the ACL has been reported to be between 22 and 41 mm, and the midbody width has been shown to be 7 to 12 mm.29,58


Figure 2. Lateral view of a right knee with the medial femoral condyle removed to reveal the insertion of the anterior cruciate ligament (ACL) on the medial wall of the lateral femoral condyle. This image demonstrates the insertion of the ACL posterior to the lateral intercondylar ridge (resident’s ridge), and the positions of the posterolateral (PL) and anteromedial (AM) ACL bundles.

The ACL is a collagen composite structure, mostly composed of type I collagen, and presents an elastic behavior that reveals the ability of the ligament to alleviate sudden deformations and characteristic relaxation of tension to reduce the risk of injury in the event of a prolonged deformation.41 The stress-strain behaviors of the ACL are nonlinear.33 Woo et al88 reported that the ultimate failure load of the ACL averaged 2160 N, while the mean ACL stiffness was 242 N/mm. A partial tear would be considered a “plastic” deformation, where the tissue has been stretched to the point where it cannot elastically recover. According to a recent systematic review, noncontact ACL injuries are most likely to occur when landing on a slightly flexed knee that is loaded by moments in 3 orthogonal planes. An internally directed tibial torque and knee valgus moment, combined with a quadriceps muscle contraction to resist the flexion moment. These forces appear to be particularly detrimental to elastic properties of the ACL.66 Partial tear occurs when the forces through the ACL surpass the yield point.41 When the ultimate strength is reached, the ACL fibers start to break until a complete rupture takes place at the so-called break point. The toe region represents the first non-linear region where collagen fibers are sequentially recruited to bear load, and it is followed by the linear region where collagen fibers temporarily deform.84

Because of its importance in ligament viability in both the native state and during reparative treatments of an ACL tear, the vascularity of the ACL has also been studied.1,28 The blood supply to the cruciate ligaments originates from the middle genicular artery, which provides 4 branches to the PCL and only 1 branch to the ACL. At the femoral and tibial insertions of the ligaments, the middle genicular vessels anastomose with a vascular subcortical network. These anastomoses are scant and therefore unlikely to be able to support the repair of a torn ligament. Injection and immunohistochemistry studies have confirmed these avascular areas.62,63

Limited literature exists regarding the definition and classification of partial ACL tears and subsequent therapeutic algorithms. A partial ACL tear combines a positive Lachman’s test with a firm endpoint. Panisset et al,61 in a prospective study of 418 cases clinically, reported that a significant degree of laxity was detected between a population with complete ACL tears (98% of the patients had a positive Lachman test and 80% had a positive pivot-shift test) and a group with partial tears (30%-64%) had a hard or delayed stop in the Lachman test and had a negative pivot-shift test.

Important characteristics of partial ACL tears are a hyperintense signal within the ACL fibers on magnetic resonance imaging (MRI), arthroscopic findings of a partial tear, and a side-to-side difference in KT-1000 criterion (<5 mm).43,71 Noyes et al59 defined these injuries according to the percentage of uninjured ACL tissue remaining at the time of arthroscopy. Using a nerve hook, the authors carefully probed the ligament and removed overlying synovium to finally assess the residual ligament present. The region of the tear, the fiber bundles in relationship to the tibia, and the estimated amount of the gross tearing was assessed. They recognized that although not totally objective, direct visualization of the gross disruption remains the only means available to quantify ACL tissue. DeFranco and Bach19 categorized partial tears based on a combination of knee laxity on physical examination and the arthroscopic appearance. Gobbi et al32 classified partial tears into 4 separate grades based on MRI findings of the affected bundle, which were confirmed at the moment of the arthroscopic surgery. Grade 1 injuries involved a partial lesion of the AM bundle, while grade 2 lesions involved a similar partial lesion of the PL bundle. Grade 3 injuries represented incomplete injury of both bundles, and grade 4 was found to be a complete tear of both bundles.

Few reports documenting spontaneous healing of partial ACL tears are available in the literature.17,35 While ACLR has demonstrated good results with different graft options for complete ACL ruptures, nonsurgical treatment and primary repair of the partial and complete tear of the ACL has been reported to fail to heal in the majority of patients.24 Recent clinical and animal studies suggest a possibility of ACL healing after primary suture of the ligament augmented with the use of growth factors and bone marrow–derived mesenchymal stem cells (BMSCs).54,74 This might be clinically important in the treatment of partial ACL tears, because growth factors and bioactive proteins play an important role in tissue healing as they can regulate key processes in tissue repair, including cell proliferation, chemotaxis, migration, cellular differentiation, and extracellular matrix (ECM) synthesis.31

ACL Repair by the Healing Response

First described by Steadman et al72 the “healing response technique” was proposed to treat tearing or avulsion of the ACL from its proximal insertion on the femur. This technique involves a microfracture of the medial wall of the lateral femoral condyle performed close to the femoral ACL footprint. This reportedly leads to the formation of a blood clot and subsequent hematoma formation at the anatomic location of the ACL insertion, causing scarring and potential attachment of the proximal ACL.

Steadman et al72 evaluated 13 skeletally immature athletes with proximal ACL tears who underwent a healing response procedure. Three (23%) patients had a reinjury 30 to 55 months after surgery. Subjective follow-up on the remaining 10 patients demonstrated resolution of pain without subjective instability or giving way, and all patients considered their knee function to be normal. At 69 months, the average Lysholm score was 96 and Tegner score was 8.5 (range, 7-10). Patient satisfaction at follow-up was 9.9 (1 = very dissatisfied and 10 = very satisfied). Clinical examination was performed on 7 of 10 patients at 35 months postoperative (range, 12-63 months). Five patients had a negative pivot-shift and 2 had a 1+ pivot-shift. KT-1000 measurements improved to 2 mm (range, 0-3 mm).

More recently, the same group evaluated 48 active middle-aged patients who underwent the healing response procedure with an average follow-up of 7.6 years (range, 2.2-13.4 years).73 The average preoperative Lysholm score was 54 (range, 10-82) and improved to an average score of 90 postoperatively (P = .001). Median Tegner activity scale at follow-up was 5 (range, 2-9). Median patient satisfaction was 10 (range, 4-10).

Wasmaier et al85 showed contrary results, demonstrating no differences between patients treated by the healing response technique or conservatively (nonsurgical) with regard to clinical scores, joint laxity, and rate of revision surgery. However, more recently, in an interesting histological study investigating spontaneously reattached tibial ACL remnants, Nguyen et al57 concluded that the human proximal one-third ACL has an intrinsic healing response with typical characteristics similar to the MCL, which can heal spontaneously.

The recent findings of ACL healing in animal models56 stimulate the interests in future translational studies to develop and evaluate the bioenhanced suture repair of torn ACLs in humans.

ACL Repair Augmented with Growth Factors

Growth factors, such as transforming growth factor beta1 (TGF-β1),90 fibroblast growth factor–2 (FGF-2),45 growth and differentiation factors 5 and 7,18 and basic-FGF (bFGF),39 have been reported to regulate and improve cellular activities and proliferation, ECM deposition, and influence the differentiation of mesenchymal stem cells (MSCs) into fibroblasts in the repair process of torn ligaments. Particularly, the growth factors outlined below have exhibited positive effects on various biological processes needed to improve ACL healing. TGF-β is a key regulator during embryologic tendon development and also plays a significant role in the early modulation of scar tissue formation during connective tissue healing.50

In Vitro Studies

Marui et al46 reported that the application of TGF-β1 resulted in increased collagen synthesis up to 1.5 times greater than controls in both MCL and ACL fibroblasts. Madry et al45 showed the enhanced healing of the human ACL by overexpression of FGF-2 via direct recombinant adeno-associated virus (rAAV) vector–mediated gene transfer.

Animal Models

In a recent study, Takayama et al77 assessed the effects of angiogenesis in ACLRs in a mice model. Angiogenesis blocking (thorough a virally transduced sFLT1 [soluble FMS-like tyrosine kinase–1]) reduced graft maturation and biomechanical strength; however, overexpression of vascular endothelial growth factor (VEGF) did not result in improvements in biomechanical strength. Kobayashi et al39 reported on the positive effect of bFGF in improving ACL tissue healing in a canine model by increased vascularity compared with the control. In the bFGF group, a bFGF-impregnated pellet was sutured to the infrapatellar fat pad close to the defect. In the control group, the same pellet without bFGF was used. More recently, Kondo et al40 studied the effect of TGF-β1 in an in vivo model of ACL injury in rabbits (n = 36). Different concentrations of TGF-β1 were utilized against no treatment acting as controls. They reported significant improvement of biomechanical and histological healing properties of injured ACLs treated with TGF-β1 compared with controls.

In vitro and animal studies using specific growth factors such as TGF-β, bFGF, VEGF, and FGF-2 demonstrated to stimulate cell proliferation and ECM synthesis and influence the differentiation of MSCs into fibroblasts in the repair process of torn ligaments.

ACL Repair Augmented with PRP

In a similar manner, PRP is known to contain several growth factors and has been the center of attention regarding noninvasive therapies. The combination of bioactive agents can mediate the tissue healing process after an injury through both the inflammatory and remodeling phases.16Platelets are involved in homeostasis, aggregation and clot formation steps, which finally leads to enhanced tissue healing.49 These processes are mediated by the release of platelet-derived growth factor (PDGF), TGF-β1, VEGF, bFGF, and epidermal growth factor through degranulation of alpha granules. Among these growth factors, PDGF and TGF-β1 have been reported to be the most critical modulators in the healing process by contributing to increased fibroblast proliferation and collagen production.22,48

Animal Models

Murray et al52 reported on a porcine model using clotted PRP in the gap of a transected ACL and concluded that there was no beneficial effect of adding PRP. It was theorized that the fibrin clot containing the platelets may have been prematurely dissolved in the intra-articular environment, leading to the failure of isolated PRP as a system for localized growth factor delivery. These observations led to the exploration of scaffolds to hold the PRP at the wound site of the ACL and protect it from early degradation. Cheng et al15 showed that the addition of PRP to the collagen hydrogel resulted in a significantly increased cellular metabolic activity, reduced apoptotic rate, and stimulation of collagen production in the cells from the immature and adolescent animals but had less effect on adult cells animals.

Clinical Studies

Seijas et al69 reported a high return to sport in 19 professional soccer players with a partial ACL tear treated with intraligamentous placement of platelet-derived growth factors into the intact bundle (Figure 3). Platelet-rich growth factors (PRGF-Endoret) were applied using the technique described by Anitua (PRGF-Endoret)5 with a spine needle in both the proximal origin of the bundle and in the middle portion thereof in an amount of 4 mL. The average time between the injury and the time of surgery was 5.8 weeks. At the end of the surgery, when the joint had been dried and all surgical instruments had been removed, another injection of PRGF-Endoret was administered (6 mL) in the articular space. Fifteen patients returned to play at an average of 16.20 weeks (1 rerupture at 7 months), while the 3 patients returned in 12.33 weeks. However, 1 patient was not able to return to sport due to the extent of their cartilage lesions. No notable complications were reported in any patients in the series, as well as no obvious bleeding or infections. A postoperative MRI study was performed in all patients and showed the remnant ACL bundle with complete ligamentization at 1 year postsurgery and good anatomic arrangement.


Figure 3. Arthroscopic view of partial tear of the anterior cruciate ligament (ACL) in a right knee treated with an injection of platelet-rich plasma (PRP) as viewed through the anteromedial portal.

While a paucity of evidence in clinical studies on the use of PRP on partial ACL tears exists, the safety and versatility of PRP injections has inspired and stimulated its therapeutic use for other pathologies. It is used extensively on a number of other orthopaedic injuries. Podesta et al64reported on 34 athletes with a partial-thickness ulnar collateral ligament (UCL) tear confirmed on MRI; 30 of 34 athletes (88%) returned to the same level of play without any complaints at an average follow-up of 70 weeks. They concluded that this study indicates that PRP was an effective option to successfully treat partial UCL tears of the elbow in athletes.

Animal models using PRP alone for ACL tears may have failed because the main structural protein within PRP was degraded by the active plasmin within the joint and the PRP was unable to remain in the ACL wound site. More studies are needed in animals to understand further the effect of PRP on the healing process in the intra-articular knee environment. While clinical studies showed a higher rate of return to sport and ACL ligamentization at 1 year follow-up when combined with PRP, further studies and longer follow-ups are required with the use of PRP in partial ACL injuries to draw definitive conclusions.

Cell Therapy

Cell therapy has been widely studied in vitro and in preclinical studies.1113 MSCs are adult stem cells from various sources, being multipotent and having the capacity of self-renewal. MSCs can differentiate into mesoderm-associated cell types such as chondrocytes, adipocytes, or osteoblasts. In vivo, they are often located in the perivascular area.11

Animal Models of MSCs ACL Repair

In a rat model of partial ACL tear, Kanaya et al36 reported that intra-articular injection of MSCs resulted in a healed ligament with superior histological scores and a greater failure load compared with nontreated control knees. In a more recent study, Oe et al60 used intra-articular injection of either fresh BMSCs or cultured MSCs at 1 week after ACL transection in a rat model. They showed that the donor cells were located within the wound site and the ACL exhibited almost normal histology, with more mature spindle cells with higher levels of TGF-β in the BMSCs group. They concluded that the direct intra-articular BMSCs injection was an effective option for the treatment of partial ACL tears.

ACL Repair MSCs Clinical Studies

In the only clinical study in humans, Centeno et al14 reported on 10 patients with ACL tears treated with an intra-ligamentous injection of autologous bone marrow concentrate and PRP using fluoroscopic guidance. ACL laxity and MRI evidence of grade 1, 2, (partial), or 3 (complete) tears was documented including patients with partial and complete ACL tears with less than 1-cm retraction. ACL tears were analyzed by MRI images pre- and postinjection. A software was used to objectively quantify changes through 5 different types of measurements of ACL pixel intensity for ligament integrity. Seven of 10 patients showed improvement in at least 4 of 5 of these objective MRI measures. The mean visual analog scale change was a decrease of 1.7 (P = .25), the mean Lower Extremity Functional Scale change was an increase of 23.3 (P = .03), and mean reported improvement was 86.7%.

Scaffolds + Suture + PRP
Animal Models

The use of collagen-based scaffolds has been shown to be effective. ACL fibroblasts have been previously shown to effectively attach, proliferate, and express collagen on collage-based scaffolds.21 Porcine small intestinal submucosa (SIS) was among the first scaffolds used to enhance the regeneration and repair of ligaments and tendons. 7,20 SIS is a collagen-based (90% of dry weight) bioabsorbable scaffold that contains cytokines and growth factors such as FGF and TGF-β.55 Fisher et al25 reported significant improvement in tissue mechanical and histological properties using a primary repair technique supplemented with SIS bioscaffold and hydrogel. There was no excessive hypertrophy of the ECM-treated ACLs, and the cross-sectional area was comparable to the sham-operated control group.

Recent in vivo work by Fleming et al26 reported no significant improvement of suture repair when supplemented with a collagen scaffold alone used for complete ACL tears in a porcine model. However, by combining a collagen scaffold with autologous platelets, Vavken et al82 demonstrated significantly improved ACL repair outcomes in a series of large animal studies, which showed superior tissue mechanical properties using primary repair augmented with a collagen-PRP hydrogel compared with suture repair alone. Additional studies have also now demonstrated that the combination of an ECM-based collagen scaffold and PRP is substantially more effective than the application of each of these factors alone.52 The mechanism behind this remains unclear, but it may be due to a synergic effect between the collagen, PRP, and other ECM molecules.

Clinical Studies

Gobbi et al32 evaluated the clinical results of suture repair of the ACL plus microfracture of the intercondylar notch and adjunctive PRP injection with 5-year follow-up in 58 athletes. They reported that 78% of the patients returned to their sports activities. A significant decrease in the side-to-side difference in anterior translation was also reported, from 4.1 mm (SD = 1.6) preoperatively to 1.4 mm (SD = 0.8) postoperatively at the 5-year follow-up. This difference was statistically significant (P < .05). Four patients had a retear during sporting activity and underwent ACLR within 2 years from the primary repair surgery. In this case series, they concluded that ACLR was an effective technique to restore knee stability and function in young individuals with acute partial ACL tears.

Biological Enhancement of the ACL

Newer approaches using scaffolds loaded with cells and growth factors could probably lead to improved rates of healing of ACL tears.75 After many years of preclinical studies, Murray et al51introduced the use of a collagen scaffold soaked with whole blood to deliver platelets in combination with a novel bioenhanced primary repair technique using a suture stent, called bridge-enhanced ACL repair (BEAR technique) and reported that it resulted in biomechanical properties of the repaired ACL equivalent to an ACLR after 3, 6, and 12 months of healing in an animal model.82 Furthermore, this novel technique of bio-enhanced repair prevented the development of cartilage lesions, which were seen 12 months after untreated ACL transection and ACLR in an animal model.51

ACLR can be associated with muscle weakness, biomechanical limitation, loss of proprioception, donor site morbidity with the use of autograft tissue, graft failure, and early posttraumatic osteoarthritis. Advancements in tissue engineering and regenerative medicine have resulted in a new interest in the biologic treatment of partial tears of the ACL. The use of novel biologic ACL repair techniques, including growth factors, PRP, stem cells, and bioscaffolds, have been reported to result in promising preclinical and short-term clinical outcomes. Further studies are necessary to define the role of these approaches in the treatment of the partial tears of ACL, to better understand the biology of the healing process, and to assess long-term outcomes.

One or more of the authors has declared the following potential conflict of interest or source of funding: R.F.L. is a consultant for and receives royalties from Arthrex, Ossur, and Smith & Nephew.

1.Alm A, Stromberg B. Vascular anatomy of the patellar and cruciate ligaments. A microangiographic and histologic investigation in the dog. Acta Chir Scand Suppl. 1974;445:2535. Google Scholar Medline
2.Amis AA. Anterior cruciate ligament replacement. Knee stability and the effects of implants. J Bone Joint Surg Br. 1989;71:819824. Google Scholar Medline
3.Amis AA, Dawkins GP. Functional anatomy of the anterior cruciate ligament. Fibre bundle actions related to ligament replacements and injuries. J Bone Joint Surg Br. 1991;73:260267. Google Scholar Medline
4.Anderson CJ, Westerhaus BD, Pietrini SD, . Kinematic impact of anteromedial and posterolateral bundle graft fixation angles on double-bundle anterior cruciate ligament reconstructions. Am J Sports Med.2010;38:15751583. Google Scholar Link
5.Anitua E. Plasma rich in growth factors: preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants. 1999;14:529535. Google Scholar Medline
6.Ardern CL, Webster KE, Taylor NF, Feller JA. Return to sport following anterior cruciate ligament reconstruction surgery: a systematic review and meta-analysis of the state of play. Br J Sports Med.2011;45:596606. Google Scholar CrossRef, Medline
7.Badylak SF, Park K, Peppas N, McCabe G, Yoder M. Marrow-derived cells populate scaffolds composed of xenogeneic extracellular matrix. Exp Hematol. 2001;29:13101318. Google Scholar CrossRef, Medline
8.Barenius B, Ponzer S, Shalabi A, Bujak R, Norlen L, Eriksson K. Increased risk of osteoarthritis after anterior cruciate ligament reconstruction: a 14-year follow-up study of a randomized controlled trial. Am J Sports Med. 2014;42:10491057. Google Scholar Link
9.Beard DJ, Murray DW, Gill HS, . Reconstruction does not reduce tibial translation in the cruciate-deficient knee an in vivo study. J Bone Joint Surg Br. 2001;83:10981103. Google Scholar CrossRef, Medline
10.Biau DJ, Tournoux C, Katsahian S, Schranz P, Nizard R. ACL reconstruction: a meta-analysis of functional scores. Clin Orthop Relat Res. 2007;458:180187. Google Scholar Medline
11.Caplan AI. All MSCs are pericytes? Cell Stem Cell. 2008;3:229230. Google Scholar CrossRef, Medline
12.Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9:641650. Google Scholar CrossRef, Medline
13.Caplan AI. Mesenchymal stem cells: the past, the present, the future. Cartilage. 2010;1:69. Google Scholar Link
14.Centeno CJ, Pitts J, Al-Sayegh H, Freeman MD. Anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow nucleated cells: a case series. J Pain Res.2015;8:437447. Google Scholar Medline
15.Cheng M, Johnson VM, Murray MM. Effects of age and platelet-rich plasma on ACL cell viability and collagen gene expression. J Orthop Res. 2012;30:7985. Google Scholar CrossRef, Medline
16.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;2:203210. Google Scholar Link
17.Costa-Paz M, Ayerza MA, Tanoira I, Astoul J, Muscolo DL. Spontaneous healing in complete ACL ruptures: a clinical and MRI study. Clin Orthop Relat Res. 2012;470:979985. Google Scholar CrossRef,Medline
18.Date H, Furumatsu T, Sakoma Y, . GDF-5/7 and bFGF activate integrin alpha2-mediated cellular migration in rabbit ligament fibroblasts. J Orthop Res. 2010;28:225231. Google Scholar Medline
19.DeFranco MJ, Bach BRJr. A comprehensive review of partial anterior cruciate ligament tears. J Bone Joint Surg Am. 2009;91:198208. Google Scholar CrossRef, Medline
20.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;29:175184. Google Scholar Link
21.Dunn MG, Liesch JB, Tiku ML, Zawadsky JP. Development of fibroblast-seeded ligament analogs for ACL reconstruction. J Biomed Mater Res. 1995;29:13631371. Google Scholar CrossRef, Medline
22.Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg. 2004;114:15021508. Google Scholar CrossRef, Medline
23.Feagin JA, Curl WW. Isolated tear of the anterior cruciate ligament: five-year follow-up study. J Orthop Sports Phys Ther. 1990;12:232236. Google Scholar CrossRef, Medline
24.Feagin JAJr, Curl WW. Isolated tear of the anterior cruciate ligament: 5-year follow-up study. Am J Sports Med. 1976;4:95100. Google Scholar Link
25.Fisher MB, Liang R, Jung HJ, . Potential of healing a transected anterior cruciate ligament with genetically modified extracellular matrix bioscaffolds in a goat model. Knee Surg Sports Traumatol Arthrosc.2012;20:13571365. Google Scholar CrossRef, Medline
26.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;28:703709. Google Scholar Medline
27.Georgoulis AD, Ristanis S, Moraiti CO, . ACL injury and reconstruction: Clinical related in vivo biomechanics. Orthop Traumatol Surg Res. 2010;96(8 suppl):S119S128. Google Scholar CrossRef, Medline
28.Gillquist J. Repair and reconstruction of the ACL: is it good enough? Arthroscopy. 1993;9:6871. Google Scholar CrossRef, Medline
29.Girgis FG, Marshall JL, Monajem A. The cruciate ligaments of the knee joint. Anatomical, functional and experimental analysis. Clin Orthop Relat Res. 1975;106:216231. Google Scholar CrossRef
30.Gobbi A, Domzalski M, Pascual J, Zanazzo M. Hamstring anterior cruciate ligament reconstruction: is it necessary to sacrifice the gracilis? Arthroscopy. 2005;21:275280. Google Scholar CrossRef, Medline
31.Gobbi A, Karnatzikos G, Mahajan V, Malchira S. Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients. Sports Health. 2012;4:162172.Google Scholar Link
32.Gobbi A, Karnatzikos G, Sankineani SR, Petrera M. Biological augmentation of ACL refixation in partial lesions in a group of athletes: results at the 5-year follow-up. Tech Orthop. 2013;28:180184. Google Scholar CrossRef
33.Holden JP, Grood ES, Korvick DL, Cummings JF, Butler DL, Bylski-Austrow DI. In vivo forces in the anterior cruciate ligament: direct measurements during walking and trotting in a quadruped. J Biomech.1994;27:517526. Google Scholar CrossRef, Medline
34.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;40:512520. Google Scholar Link
35.Ihara H, Miwa M, Deya K, Torisu K. MRI of anterior cruciate ligament healing. J Comput Assist Tomogr.1996;20:317321. Google Scholar CrossRef, Medline
36.Kanaya A, Deie M, Adachi N, Nishimori M, Yanada S, Ochi M. Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model. Arthroscopy. 2007;23:610617. Google Scholar CrossRef, Medline
37.Kartus J, Movin T, Karlsson J. Donor-site morbidity and anterior knee problems after anterior cruciate ligament reconstruction using autografts. Arthroscopy. 2001;17:971980. Google Scholar CrossRef, Medline
38.Kennedy JC, Weinberg HW, Wilson AS. The anatomy and function of the anterior cruciate ligament. As determined by clinical and morphological studies. J Bone Joint Surg Am. 1974;56:223235. Google Scholar CrossRef, Medline
39.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;5:189194.Google Scholar CrossRef, Medline
40.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;33:188196. Google Scholar Link
41.Kwan MK, Lin TH, Woo SL. On the viscoelastic properties of the anteromedial bundle of the anterior cruciate ligament. J Biomech. 1993;26:447452. Google Scholar CrossRef, Medline
42.Li H, Tao H, Hua Y, Chen J, Li Y, Chen S. Quantitative magnetic resonance imaging assessment of cartilage status: a comparison between young men with and without anterior cruciate ligament reconstruction. Arthroscopy. 2013;29:20122019. Google Scholar CrossRef, Medline
43.Liu SH, Osti L, Henry M, Bocchi L. The diagnosis of acute complete tears of the anterior cruciate ligament. Comparison of MRI, arthrometry and clinical examination. J Bone Joint Surg Br.1995;77:586588. Google Scholar Medline
44.Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007;35:17561769. Google Scholar Link
45.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;41:194202. Google Scholar Link
46.Marui T, Niyibizi C, Georgescu HI, . Effect of growth factors on matrix synthesis by ligament fibroblasts. J Orthop Res. 1997;15:1823. Google Scholar CrossRef, Medline
47.Mastrangelo AN, Magarian EM, Palmer MP, Vavken P, Murray MM. The effect of skeletal maturity on the regenerative function of intrinsic ACL cells. J Orthop Res. 2010;28:644651. Google Scholar Medline
48.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;27:10331042. Google Scholar CrossRef, Medline
49.Mishra A, Woodall JJr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med. 2009;28:113125. Google Scholar CrossRef, Medline
50.Muller B, Bowman KFJr, Bedi A. ACL graft healing and biologics. Clin Sports Med. 2013;32:93109. Google Scholar CrossRef, Medline
51.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;41:17621770. Google Scholar Link
52.Murray MM, Palmer M, Abreu E, Spindler KP, Zurakowski D, Fleming BC. 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;27:639645. Google Scholar CrossRef, Medline
53.Murray MM, Spindler KP, Abreu E, . Collagen-platelet rich plasma hydrogel enhances primary repair of the porcine anterior cruciate ligament. J Orthop Res. 2007;25:8191. Google Scholar CrossRef, Medline
54.Murray MM, Spindler KP, Ballard P, Welch TP, Zurakowski D, Nanney LB. Enhanced histologic repair in a central wound in the anterior cruciate ligament with a collagen-platelet-rich plasma scaffold. J Orthop Res. 2007;25:10071017. Google Scholar CrossRef, Medline
55.Musahl V, Abramowitch SD, Gilbert TW, . 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;22:214220. Google Scholar CrossRef, Medline
56.Nguyen DT, Geel J, Schulze M, . Healing of the goat anterior cruciate ligament after a new suture repair technique and bioscaffold treatment. Tissue Eng Part A. 2013;19:22922299. Google Scholar CrossRef,Medline
57.Nguyen DT, Ramwadhdoebe TH, van der Hart CP, Blankevoort L, Tak PP, van Dijk CN. Intrinsic healing response of the human anterior cruciate ligament: an histological study of reattached ACL remnants. J Orthop Res. 2014;32:296301. Google Scholar CrossRef, Medline
58.Norwood LAJr, Cross MJ. The intercondylar shelf and the anterior cruciate ligament. Am J Sports Med.1977;5:171176. Google Scholar Link
59.Noyes FR, Mooar LA, Moorman CT3rd, McGinniss GH. Partial tears of the anterior cruciate ligament. Progression to complete ligament deficiency. J Bone Joint Surg Br. 1989;71:825833. Google Scholar Medline
60.Oe K, Kushida T, Okamoto N, . New strategies for anterior cruciate ligament partial rupture using bone marrow transplantation in rats. Stem Cells Dev. 2011;20:671679. Google Scholar CrossRef, Medline
61.Panisset JC, Duraffour H, Vasconcelos W, . Clinical, radiological and arthroscopic analysis of the ACL tear. A prospective study of 418 cases [in French]. Rev Chir Orthop Reparatrice Appar Mot. 2008;94(8 suppl):362368. Google Scholar CrossRef, Medline
62.Petersen W, Tillmann B. Anatomy and function of the anterior cruciate ligament [in German]. Orthopade.2002;31:710718. Google Scholar CrossRef, Medline
63.Petersen W, Tillmann B. Structure and vascularization of the cruciate ligaments of the human knee joint. Anat Embryol (Berl). 1999;200:325334. Google Scholar CrossRef, Medline
64.Podesta L, Crow SA, Volkmer D, Bert T, Yocum LA. Treatment of partial ulnar collateral ligament tears in the elbow with platelet-rich plasma. Am J Sports Med. 2013;41:16891694. Google Scholar Link
65.Proffen BL, Sieker JT, Murray MM. Bio-enhanced repair of the anterior cruciate ligament. Arthroscopy.2015;31:990997. Google Scholar CrossRef, Medline
66.Quatman CE, Quatman-Yates CC, Hewett TE. A ‘plane’ explanation of anterior cruciate ligament injury mechanisms: a systematic review. Sports Med. 2010;40:729746. Google Scholar CrossRef, Medline
67.Robson AW. VI. Ruptured crucial ligaments and their repair by operation. Ann Surg. 1903;37:716718. Google Scholar Medline
68.Rosc D, Powierza W, Zastawna E, Drewniak W, Michalski A, Kotschy M. Post-traumatic plasminogenesis in intraarticular exudate in the knee joint. Med Sci Monit. 2002;8:CR371CR378. Google Scholar Medline
69.Seijas R, Ares O, Cusco X, Alvarez P, Steinbacher G, Cugat R. Partial anterior cruciate ligament tears treated with intraligamentary plasma rich in growth factors. World J Orthop. 2014;5:373378. Google Scholar CrossRef, Medline
70.Shah VM, Andrews JR, Fleisig GS, McMichael CS, Lemak LJ. Return to play after anterior cruciate ligament reconstruction in National Football League athletes. Am J Sports Med. 2010;38:22332239. Google Scholar Link
71.Sonnery-Cottet B, Colombet P. Partial tears of the anterior cruciate ligament. Orthop Traumatol Surg Res. 2016;102(1 suppl):S59S67. Google Scholar CrossRef, Medline
72.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;19:813. Google Scholar Medline
73.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;25:255260. Google Scholar CrossRef, Medline
74.Steadman JR, Rodkey WG. Role of primary anterior cruciate ligament repair with or without augmentation. Clin Sports Med. 1993;12:685695. Google Scholar Medline
75.Steiner ME, Murray MM, Rodeo SA. Strategies to improve anterior cruciate ligament healing and graft placement. Am J Sports Med. 2008;36:176189. Google Scholar Link
76.Strand T, Mølster 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;125:217221. Google Scholar CrossRef, Medline
77.Takayama K, Kawakami Y, Mifune Y, . The effect of blocking angiogenesis on anterior cruciate ligament healing following stem cell transplantation. Biomaterials. 2015;60:919. Google Scholar CrossRef, Medline
78.Tashman S, Kolowich P, Collon D, Anderson K, Anderst W. Dynamic function of the ACL-reconstructed knee during running. Clin Orthop Relat Res. 2007;454:6673. Google Scholar CrossRef, Medline
79.Taylor DC, Posner M, Curl WW, Feagin JA. Isolated tears of the anterior cruciate ligament: over 30-year follow-up of patients treated with arthrotomy and primary repair. Am J Sports Med. 2009;37:6571. Google Scholar Link
80.Taylor SA, Khair MM, Roberts TR, DiFelice GS. Primary repair of the anterior cruciate ligament: A systematic review. Arthroscopy. 2015;31:22332247. Google Scholar CrossRef, Medline
81.Tsai AG, Wijdicks CA, Walsh MP, Laprade RF. Comparative kinematic evaluation of all-inside single-bundle and double-bundle anterior cruciate ligament reconstruction: a biomechanical study. Am J Sports Med. 2010;38:263272. Google Scholar Link
82.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;28:672680. Google Scholar CrossRef, Medline
83.Vavken P, Murray MM. The potential for primary repair of the ACL. Sports Med Arthrosc. 2011;19:4449.Google Scholar CrossRef, Medline
84.Viidik A. Simultaneous mechanical and light microscopic studies of collagen fibers. Z Anat Entwicklungsgesch. 1972;136:204212. Google Scholar CrossRef, Medline
85.Wasmaier J, Kubik-Huch R, Pfirrmann C, Grehn H, Bieg C, Eid K. Proximal anterior cruciate ligament tears: the healing response technique versus conservative treatment. J Knee Surg. 2013;26:263271. Google Scholar Medline
86.Wittek A. Über Verletzungen der Kreuzbänder des Kniegelenkes. Dtsch Z Chir. 1927;200:491515. Google Scholar CrossRef
87.Wittek A. Replacement of the cruciate ligament with patellar tendon. Schweiz Med Wochenschr.1935;65:103104. Google Scholar
88.Woo SL, Debski RE, Withrow JD, Janaushek MA. Biomechanics of knee ligaments. Am J Sports Med.1999;27:533543. Google Scholar Link
89.Woo SL, Vogrin TM, Abramowitch SD. Healing and repair of ligament injuries in the knee. J Am Acad Orthop Surg. 2000;8:364372. Google Scholar CrossRef, Medline
90.Xie J, Wang C, Huang DY, . 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;46:890898. Google Scholar CrossRef, Medline
91.Zantop T, Brucker PU, Vidal A, Zelle BA, Fu FH. Intraarticular rupture pattern of the ACL. Clin Orthop Relat Res. 2007;454:4853. Google Scholar CrossRef, Medline
92.Zantop T, Petersen W, Sekiya JK, Musahl V, Fu FH. Anterior cruciate ligament anatomy and function relating to anatomical reconstruction. Knee Surg Sports Traumatol Arthrosc. 2006;14:982992. Google Scholar CrossRef, Medline
93.Zhou MW, Gu L, Chen YP, . Factors affecting proprioceptive recovery after anterior cruciate ligament reconstruction. Chin Med J (Engl). 2008;121:22242228. Google Scholar Medline
94.Ziegler CG, Pietrini SD, Westerhaus BD, . Arthroscopically pertinent landmarks for tunnel positioning in single-bundle and double-bundle anterior cruciate ligament reconstructions. Am J Sports Med.2011;39:743752. Google Scholar Link

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