Level V Evidence
Biologics, Stem Cells, Growth Factors, Platelet-Rich Plasma, Hemarthrosis, and Scaffolds May Enhance Anterior Cruciate Ligament Surgical Treatment

https://doi.org/10.1016/j.arthro.2022.11.006Get rights and content

Abstract

Biologics including mesenchymal stem cells (MSCs), growth factors, and platelet-rich plasma may enhance anterior cruciate ligament (ACL) reconstruction and even ACL primary repair. In addition, hemarthrosis after acute ACL injury represents a source of biologic factors. MSCs can differentiate into both fibroblasts and osteoblasts, potentially providing a transition between the ligament or graft and bone. MSCs also produce cytokines and growth factors necessary for cartilage, bone, ligament, and tendon regeneration. MSC sources including bone marrow, synovium, adipose tissue, ACL-remnant, patellar tendon, and umbilical cord. Also, scaffolds may represent a tool for ACL tissue engineering. A scaffold should be porous, which allows cell growth and flow of nutrients and waste, should be biocompatible, and might have mechanical properties that match the native ACL. Scaffolds have the potential to deliver bioactive molecules or stem cells. Synthetic and biologically derived scaffolds are widely available. ACL reconstruction with improved outcome, ACL repair, and ACL tissue engineering are promising goals.

Level of Evidence

Level V, expert opinion.

Section snippets

Use of MSCs in ACL Repair and Reconstruction

MSCs are multipotent progenitor cells first identified in bone marrow but have since been isolated from many tissues (Table 1). Notably, MSCs from varying sources have differing regenerative potential. In the context of ACL surgery, MSCs can differentiate into both fibroblasts and osteoblasts, potentially providing a transition between the graft and bone tunnel identical to that found in an uninjured ACL.7 MSCs also produce an array of cytokines and growth factors necessary for cartilage, bone,

Scaffolds Used in ACL Repair

It has been hypothesized that the relatively poor healing response of the native ACL compared to extra-articular ligaments such as the medial collateral ligament is due to lack of mechanical stabilization after rupture. The ACL is surrounded by constantly flowing synovial fluid, which washes away any structural blood clot and prevents this provisional scaffold formation. Biologic and synthetic scaffolds have been introduced as an adjunct to ACL repair. The ideal scaffold should include a highly

Combinations of Scaffolds and MSCs

For MSCs to potentially benefit the osteointegration process, they must be successfully delivered to the graft-bone interface. As previously discussed, many scaffolds have been engineered to deliver substrates at this junction, maintain the biology of the tendon bone interface, and degrade without causing damage.

Hemarthrosis Composition After ACL Injury

The intra-articular environment after an acute ACL injury may impact the healing ability of a repair or reconstruction procedure. Several studies have analyzed the molecular composition of synovial fluid after acute ACL injury. The focus of these studies was to understand the association of inflammatory factors and cartilage degradation after injury and several inflammatory markers and biomarkers of cartilage degradation, bony modeling, and hemarthrosis were identified. Patients with higher

Conclusions

The optimal scaffold composition for use in ACL reconstruction or repair has yet to be determined. The majority of scaffolds analyzed and described in the current literature are synthetic. Understanding the utility of biologic scaffolds, such as collagen-based scaffolds, have demonstrated significant potential.

The optimal type or source of MSCs for ACL reconstruction or repair remains to be identified. The limited availability of cells may require tissue expansion in culture to achieve an

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    The authors report that they have no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material.

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