Biologic Adjuvants for the Management of Osteochondral Lesions of the Talus

MaCalus V. Hogan, MD, MBA; Justin J. Hicks, MD; Monique C. Chambers, MD, MSL; John G. Kennedy, MD, FRCS

Disclosures

J Am Acad Orthop Surg. 2019;27(3):e105-e111. 

In This Article

Abstract and Introduction

Abstract

Surgical techniques for the management of recalcitrant osteochondral lesions of the talus have improved; however, the poor healing potential of cartilage may impede long-term outcomes. Repair (microfracture) or replacement (osteochondral transplants) is the standard of care. Reparative strategies lead to production of fibrocartilage, which, compared with the native type II articular cartilage, has decreased mechanical and wear properties. The success of osteochondral transplants may be hindered by poor integration between grafts and host that results in peripheral cell death and cyst formation. These challenges have led to the investigation of biologic adjuvants to augment treatment. In vitro and in vivo models have demonstrated promise for cartilage regeneration by decreasing inflammatory damage and increasing the amount of type II articular cartilage. Further research is needed to investigate optimal formulations and time points of administration. In addition, clinical trials are needed to investigate the long-term effects of augmentation.

Introduction

Osteochondral lesions of the talus (OLT) pose clinical and surgical challenges to orthopaedic surgeons. Approximately two million ankle sprains occur in the United States annually, with up to 50% of patients sustaining concurrent cartilage injury.[1,2] Furthermore, ankle fractures are associated with a high risk (up to 73%) for cartilage injury.[1] Chondrocytes are the primary cell type in cartilage and have little capacity for self-renewal because of limited vascularity, making OLT management challenging.

The optimal treatment modality for an OLT is unclear. Loveday et al,[3] in a Cochrane review, concluded that there is insufficient evidence from current trials to determine which treatment strategies are best for managing OLT in adults. Nonsurgical management involves nonsteroidal anti-inflammatory medication and limiting physical activity. The success rates of nonsurgical treatment, in minimally symptomatic patients, have been reported to be 86%, compared with 49% in moderately symptomatic patients based on acute symptoms and not long-term cartilage healing.[4] Surgical management is indicated in symptomatic patients and possibly in patients with sizeable defects whose condition does not improve under conservative management.

Surgical management of OLT currently focuses either on reparative cell-based therapies such as microfracture or on replacement strategies such as autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, or osteochondral autologous transplantations. Cell-based therapy involves local recruitment or delivery of cells with chondrocyte properties, whereas transplantation involves transferring cartilage explants or cells to the defect site. Although midterm studies report improved outcomes for these treatments, many patients still experience persistent pain.[5] This may be due to biologic shortcomings inherent with each approach. Cell-based reparative therapies have proteoglycan depletion and chondrocyte death at 1-year follow-up, and the fibrocartilage that is generated possesses inferior mechanical and biologic properties compared with the native hyaline articular cartilage.[6–8] With replacement strategies, concerns exist regarding poor graft integration, cell death, graft degeneration, and cyst formation.[9]

Minced juvenile articular cartilage is a novel option for large or refractory osteochondral lesions. This option entails the use of allograft cartilage harvested from donors less than 13-year old.[10] It has been used since 2007 mostly in the knee and has been shown to contain up to 10 times the cellular density of adult chondrocytes with improved ability to retain articular cartilage phenotype, theoretically leading to decreased production of fibrocartilage.[10] Early results from case reports and case series demonstrate good-to-excellent clinical outcomes; however, more robust and long-term clinical studies are needed to evaluate the efficacy of juvenile articular cartilage for the management of osteochondral defects of the talus.[10–12]

Concerns with current treatment modalities have led to recent studies investigating the role of biologic adjuncts in augmenting cartilage healing and the management of osteochondral lesions.

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