The natural history and poor healing potential of ACL injury has been described in the literature. In a prospective study, Noyes et al. estimated that 50% of patients with partial tears affecting more than half of the ACL would progress to complete ACL insufficiency after conservative treatment [14]. Additionally, a study by Braggion et al. reported that some patients undergoing arthroscopy during the acute stage of ACL injury were classified as suffering an incomplete ACL lesion, whereas arthroscopy performed during the chronic stage of injury revealed a complete tear in all cases [16]. Sommerlath et al. reported a mean Lysholm score of 93 points in 22 patients after acute partial ACL tear [17]. Nineteen of these ACL injuries were treated conservatively, while three underwent surgical repair of the torn ligamentous fibers. In contrast to Sommerlath et al., Buckley et al. reported that only 44% of 25 patients were able to resume sports after conservative treatment of arthroscopically documented partial ACL tears [18]. Fujimoto et al. evaluated conservative treatment and spontaneous healing of partial ACL tears in low demand patients [19]. In his study, 74% of patients had a stable knee at 16 months post-injury.

Although the first ACL repair has been described as early as 1895, primary suture repair of the torn portions of the ACL was popularized five decades ago [20, 21]. Feagin et al. reported a technique of ACL repair after acute injury using a polyglycolic acid suture woven through the tibial stump and passed up through bone tunnels in the femur [22]. Long-term follow-up studies demonstrated that this technique led to failure rates up to 90% and was therefore abandoned in favor of ACL reconstruction [14, 22, 23]. Despite these reports, recent investigations have demonstrated the potential of ACL healing after primary suture repair of the ligament augmented with the use of growth factors and bone marrow-derived mesenchymal stem cells (MSCs) [24–28].

Tissue healing is dependent on a number of bioactive substances that coordinate processes of healing such as cellular differentiation, proliferation, migration, and the deposition of supportive extracellular matrices. These factors can be found in abundance within platelet-rich plasma (PRP) and have been shown to enhance many stages of tissue repair [29]. In the clinical setting, PRP is typically used to stimulate the natural healing cascade and to augment tissue regeneration by providing a concentrated release of platelet-derived factors directly at the site of injury. Platelet-rich plasma is isolated after centrifugation of autologous venous blood, usually extracted and processed using a commercially available system. Importantly, it has been shown that there is significant variability in PRP growth factor constituents, depending on the method used for separation. Among the growth factors contained in PRP, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), bone morphogenetic protein (BMP), and transforming growth factor beta (TGF-β) are notable constituents that have been shown to enhance ligamentous healing.

The effects of plasma rich in growth factors on return-to-play in a series of patients suffering from partial tearing of the ACL was examined by Seijas et al. [30]. The majority of these active patients returned to pre-injury activity levels after treatment, and follow-up MRI imaging typically demonstrated complete restoration of ligamentous integrity after 1 year. In a study by Kobayashi et al., improved vascularity and ligament healing of injured canine ACL was demonstrated following application of basic fibroblast growth factor (bFGF) [31]. Targeted application of bioactive factors in other animal models such as transforming growth factor beta 1 (TGF-β1), growth differentiation factor 5 (GDF5), and bone morphogenetic protein 2 (BMP2) have demonstrated enhanced collagen synthesis and healing response in treatment of ligamentous injury [32–34]. Other research, however, has failed to demonstrate enhanced ACL repair in animal models using PRP augmentation [6].

Mesenchymal stem cells are multipotent cells that reside in a variety of tissues including bone marrow, muscle, synovium, and adipose tissue. These precursor cells have self-renewing capabilities and are able to differentiate into a number of tissue types, making them an attractive target for cellular therapy in a range of clinical applications [35, 36]. There is potential for these cells to be used in reparative treatments for ACL injury due to their shared characteristics with ligament outgrowth cells [24, 37]. There are specific deficiencies of cellular repair that impact healing of injured ACL tissue, and MSC therapies have the capacity to influence reparative processes at the cellular and molecular level. One of the earliest methods used to augment healing processes after ACL injury was described by Steadman and involved microfracture within the intercondylar notch to release elements containing MSCs and growth factors contained within the marrow, which had the proposed effect of aiding clot formation and augmenting cellular repair processes [25, 38].

Our center has analyzed 5-year clinical outcomes after primary suture repair of partial ACL tears in addition to microfracture about the ligament footprint within the intercondylar notch, followed by application of PRP to the repair site [15]. Of the treated cohort, 78% returned to sporting activities, and there was a significant decrease in the side-to-side difference in anterior tibial translation at final follow-up. Based on this data, it was concluded that this technique could be used effectively to restore knee stability and enable return-to-sport in young patients treated for acute partial ACL tear. Currently, our preferred method of biologic augmentation in cases of partial ACL repair involves application of bone marrow aspirate concentrate to the repair site (Fig. 52.2).

There have been other reported series that have examined the use of intra-articular injection of bone marrow aspirate concentrate to treat ACL injury that have demonstrated improvement in ligamentous integrity according to MRI criteria at follow-up assessment [39]. Biologic augmentation of reparative and reconstructive methods to treat ACL injury will continue to evolve, and work will continue to determine the ideal constituents of PRP and MSC preparations that will optimize tissue healing [9].

Techniques that involve biologic augmentation of ACL repair in cases of partial ACL injury, and their role in restoring knee stability, will continue to progress. The potential for these agents to act synergistically in biologic cascades of cellular repair is encouraging; however, clinical application of these factors needs further study. As knowledge of cellular and molecular biology progresses and technological advances in tissue engineering proceed, composites of cell-scaffold materials will likely lead to greater advancements in therapeutic approaches to restore near-normal anatomy in cases of ligamentous injury. In cases of ACL injury, such composite treatments would be capable of providing structural support and an environment partially sequestered from circulating plasmin, while also providing growth factors and precursor cells to enhance reparative processes.