Sage Journals: Discover world-class research

Abstract

Objective

Numerous basic science articles have published evidence supporting the use of biologic augmentation in the treatment of osteochondral lesions of the talus (OLT). However, a comprehensive evaluation of the clinical outcomes of those treatment modalities in OLT has yet to be published. The purpose of this review is to provide an evidence-based overview of clinical outcomes following biologic augmentation to surgical treatments for OLT.

Design

A comprehensive literature review was performed. Two commonly used surgical techniques for the treatment of OLT—bone marrow stimulation and osteochondral autograft transfer—are first introduced. The review describes the operative indications, step-by- step operative procedure, clinical outcomes, and concerns associated with each treatment. A review of the currently published basic science and clinical evidence on biologic augmentation in the surgical treatments for OLT, including platelet-rich plasma, concentrated bone marrow aspirate, and scaffold-based therapy follows.

Results

Biologic agents and scaffold-based therapies appear to be promising agents, capable of improving both clinical and radiological outcomes in OLT. Nevertheless, variable production methods of these biologic augmentations confound the interpretation of clinical outcomes of cases treated with these agents.

Conclusions

Current clinical evidence supports the use of biologic agents in OLT cases. Nonetheless, well-designed clinical trials with patient-specific, validated and objective outcome measurements are warranted to develop standardized clinical guidelines for the use of biologic augmentation for the treatment of OLT in clinical practice.

Keywords

osteochondral lesions of talus biologic platelet-rich plasma concentrated bone marrow aspirate scaffold-based therapy bone marrow stimulations autologous osteochondral transplantation

Introduction

Osteochondral lesions of the talus (OLT) are a commonly encountered foot and ankle disorders. In the majority of cases, patients with this pathology have a history of ankle sprains and/or fractures.¹ A recent systematic review demonstrated that as many as 50% of primary OLTs failed to resolve using conservative treatment, while operative treatment—including both reparative and replacement techniques—demonstrated good to excellent clinical outcomes in nearly 85% of cases.² Despite the favorable reported outcomes following operative treatment, however, inevitable deterioration of the regenerated or grafted cartilage has been documented in the literature.^3-6 This observed decline has been proposed to result from a combination of mechanical and biological impairments in the injured ankle joint.^7-10

Biologic agents, including platelet-rich plasma (PRP) and concentrated bone marrow aspirate (CBMA), as well as scaffold-based therapy have the potential to improve the quality of cartilage repair and prevent the long-term deterioration of the joint in OLT. While numerous basic science articles show evidence that supports the use of these biologic augmentations for the treatment of cartilage pathology,^11-15 a comprehensive evaluation of the clinical outcomes of those treatment modalities in OLT has yet to be published.

The purpose of this review is to provide an evidence-based overview of clinical outcomes following biologic augmentation of surgical treatments for OLT.

Surgical Treament Modalities of OLT

Bone Marrow Stimulation

Bone marrow stimulation (BMS) is a reparative procedure that is the most common operative treatment choice for OLT. Current indication for BMS is in patients with smaller lesions up to 150 mm² in size or 15 mm in diameter.^7,8 The procedure is carried out arthroscopically in the following steps: (1) debridement of the unstable cartilage and necrotic bone, (2) debridement of the calcified layer, and (3) penetration of the subchondral bone plate (SBP) using a microfracture pick or small diameter drill ( Fig. 1 ).^15,16 The procedure aims to stimulate mesenchymal stem cell (MSC) proliferation and promote fibrous cartilage repair tissue within the OLT defect.¹⁷

Figure 1.

(a-d) Unstable cartilage, necrotic bone, and the calcified layer of cartilage are debrided using an angled curette and a motorized suction shaver until the stable rim of the remaining cartilage is exposed. (e) Bone marrow stimulation (BMS) is performed using a microfracture pic or drill to penetrate the subchondral bone plate. (f) Blood from the created holes is confirmed when inflow pressure of saline is decreased or stopped. (g) Biologics can be injected into the bed of the lesion, precisely at the site of the defect.

BMS has shown promising functional outcomes in clinical studies, with approximately 85% of patients achieving good to excellent results.^2,18,19 To our knowledge, the longest follow-up after BMS was reported by van Bergen et al.²⁰ on the outcomes of 50 patients who were followed for a mean of 141 months. The authors reported that the mean American Orthopaedic Foot and Ankle Society (AOFAS) score for overall functional was 88 out of 100 possible points.²⁰ Many investigators have supported the good functional outcomes following BMS with short- to mid-term evaluations of athletic populations.^21-23

Despite the successful outcomes following BMS for OLT, deterioration of the regenerated fibrous cartilage infill at the defect site produced by BMS is inevitable.^3-6 Ferkel et al.⁴ found deterioration in 35% of patients within 5 years following BMS. Lee et al.⁵ reported that only 30% of patients who received BMS showed lesion integration during second look arthroscopy 12 months postoperatively. van Bergen et al.²⁰ reported that one-third of patients progressed by one grade of arthritis severity on standard radiographs, although the initial success of BMS was maintained throughout the mean follow-up period of 141 months.

The joint deterioration observed following BMS may be the result of a combination of both mechanical and biologic factors. Regenerated fibrous cartilage is mechanically inferior to hyaline cartilage.^24,25Lesion characteristics, including lesion size (current criteria, 150 mm² or 15 mm in diameter)^7,8 and location (talar shoulder or nonshoulder)⁹ may affect the rate of success of BMS for OLT. Recent attention has turned to the SBP, which provides significant joint loading support.^26,27 When the SBP is diminished, either by the disease process itself or by overzealous BMS, mechanical support will be reduced compromising cartilage longevity.

Biologically, articular cartilage has poor self-repair capabilities due to the tissue’s avascularity and hypocellularity.^28,29 Although the fibrous cartilage stimulated by BMS initially forms a fibrin clot that differentiates into chondrocyte-like cells that deposited type-II collagen at the site of the defect, proteoglycan depletion, chondrocyte death, and deposition of type-I collagen have been reported at 1 year postoperatively.³⁰ Fibrocartilage may lack the biological and structural capacity to prevent fluid ingress under hydrostatic loading, leading to the collapse of the stimulated infill.³¹ Recent studies have suggested that intra-articular inflammatory cytokine levels are elevated in an injured ankle joint compared with a healthy joint.^32,33 Animal studies showed that these catabolic reactions increase the risk of developing degenerative arthritis, even in mechanically stabilized joints.^34,35

A biologic agent that can reduce inflammation and provide a chondrogenic biologic milieu would therefore be advantageous.

Autologous Osteochondral Transplantation

Autologous osteochondral transplantation (AOT) is a replacement, rather than reparative, treatment option for OLT. The goal of the procedure is to restore the native architecture of the chondral surface and subchondral bone plate by inserting a cylindrical autologous osteochondral graft, typically from a non-weightbearing portion of the ipsilateral femoral condyle, into the site of the defect.¹⁷ AOT is traditionally indicated in patients with a lesion greater than 150 mm² or 15 mm in diameter, for cystic lesions, or in cases of failed previous BMS.^7,8 This technique consists of the following steps: (1) osteotomy of the malleolus to enable direct lesion visualization, (2) BMS to the surrounding healthy bone, (3) removal of the talar lesion accompanied by overdrill to create a slightly longer graft site than the harvested plug, (4) graft harvest from a non-weightbearing portion of the ipsilateral femoral condyle, and (5) insertion of the graft(s) into the recipient site ( Fig. 2 ).³⁶

Figure 2.

(a) Tibial chevron osteotomy is performed to provide direct visualization of the lesion. (b) Bone marrow stimulation (BMS) is performed in the surrounding healthy bone. (c) Overdrill is applied to make the created recipient site slightly longer than the harvested graft. (d) The osteochondral graft is harvested from a non-weightbearing portion of the femoral condyle ipsilateral to the OLT. (e) The graft/s is/are inserted into the created recipient site. Illustration is a copyright of and reproduced with permission from J.G. Kennedy, MD. Reproduction without express written consent is prohibited.

Several studies have reported good clinical outcomes following AOT at both short- and mid-term follow-up.^36-39 A systematic review reported good to excellent outcomes following AOT in 243/279 patients (87%),² and several studies showed that 63% to 95% of athletes return to their previous level of activity following this procedure.^36,37,40,41 Despite its apparent success and favorable short- and medium-term outcome profile; however, to our knowledge no study has described the procedure’s long-term (10+ years) outcomes.

While the reported positive clinical outcomes do not seem to significantly deteriorate over time,³⁶ some concerns have been raised in both basic and clinical studies.^42-46 Poor integration of the graft surface with the native tissue,^42,43 cyst formation around the graft site, and deterioration of the graft cartilage⁴⁶ have all been described following AOT procedure.

Like BMS, the success of AOT for OLT may be limited by a combination of mechanical and biologic factors. A biomechanical study by Fansa et al.⁴⁷ showed that a mere 1.0 mm of graft protrusion above the level of the native cartilage increased the contact pressure on the graft surface almost 7-fold. In addition, because tibial osteotomy is frequently used to enable visualization of the lesion in AOT, the procedure carries the risk of mal-/nonunion at the site of the osteotomy.⁴⁶ This inherent risk can cause mechanical abnormalities in a fixed ankle joint and accompanied by an elevated level of intra-articular inflammatory cytokines may result in posttraumatic ankle osteoarthritis.^10,32,33 Furthermore, structural differences between talar and knee articular cartilage may produce incompatible mechanical properties.⁴⁸ Finally, knee cartilage contains cytokines not typically seen in ankle cartilage, including MMP-8 (neutrophil collagenase), which can produce a catabolic response in the reconstructed ankle joint and contribute to graft failure.⁴⁹ A biologic agent may therefore influence the quality of integration and longevity of the AOTS graft in the talus.

Biologic Augmentation for Cartilage Repair

Platelet-Rich Plasma

Platelet-rich plasma (PRP) is an autologous blood product that contains at least twice the concentration of platelets compared with baseline values, or >1.1 × 10⁶ platelets/μL. Physiologically, platelets contain growth factors and cytokines that participate in tissue healing.⁵⁰ Platelets could also potentially attract MSCs to a site of interest.⁵¹

PRP is produced using a simple bedside procedure: Blood is drawn from a peripheral vein and centrifuged using a commercially available centrifuge system. Several commercially available PRP centrifuge modalities, timing protocols for centrifugation of harvested blood, and activation methods of PRP have been described.^50,52,53 The contents of the plasma—including platelets, cells, growth factors, and cytokines—are therefore variable, even within a single individual,⁵⁰ and no standardized PRP production method has been established to date.

Several basic science in vitro and vivo studies have examined the proposed positive effects of PRP on cartilage repair. A systematic review performed by Smyth et al. showed that 18 of 21 (85.7%) basic science articles (12 in vitro, 8 in vivo, 1 both in vitro and in vivo) described a positive effect of PRP on cartilage repair. PRP was applied as a concomitant biological adjuvant during BMS and implant, scaffold, and graft insertion in vivo. The authors reported that PRP increased chondrocyte and mesenchymal stem cell proliferation, proteoglycan deposition, and type II collagen deposition and inhibited the effect of catabolic cytokines.¹¹ More recently, Symth et al.⁵⁴ investigated the effect of PRP as an adjunct to AOT in a rabbit model. The authors found that application of PRP at the time of AOT improved the integration of the osteochondral graft at the cartilage interface and decreased graft degeneration.⁵⁴ Finally, Boakye et al.⁵⁵ found that TGF-β1 expression was increased in rabbits treated with AOT and PRP compared with those with AOT and saline, and concluded that PRP could have a chondrogenic effect in vivo. These studies suggest that PRP could be used as a beneficial adjunct to BMS and AOT to improve graft survival and long-term outcomes.

While the positive effects of PRP on degenerative osteoarthritis have been demonstrated in several level 1 clinical evidence studies,^56-62 to our knowledge only 3 comparative studies have evaluated the use of PRP in OLT. Mei-Dan et al.⁶³ (level of evidence [LOE]: II) prospectively compared clinical outcomes following PRP or hyaluronic acid (HA) injection in 32 patients with a 6-month follow-up. The authors reported that PRP injection provided significantly better clinical scores than HA. Guney et al.⁶⁴ (LOE: II) performed a randomized prospective study comparing the clinical and functional outcomes of 16 patients treated with BMS with 19 patients who received BMS with PRP. At the average follow-up of 16.2 months, the authors found that all cases included in the study had significantly improved clinical outcomes, but the PRP group had superior outcomes to the BMS-only group. Finally, Görmeli et al.⁶⁵ (LOE: I) compared the effect of PRP and HA following BMS for OLT in a prospective randomized clinical trial. Among 40 patients with an average of 15.3-month follow-up, clinical improvement after PRP treatment was significantly greater than after HA or saline injection. Thus, though few comparisons are currently available in the literature, results suggest that using PRP for treating OLT may improve outcomes compared with HA or no intervention. Nevertheless, because of the noted variability in PRP content, a definitive conclusion is yet to be reached.

Concentrated Bone Marrow Aspirate

Concentrated bone marrow aspirate (CBMA) is a reservoir of MSCs, growth factors, and cytokines that have been purported to improve the quality of cartilage repair tissue. This blood product is produced by centrifuging bone marrow aspirate (BMA) harvested from the iliac crest using a trocar at the time of surgery for OLT.

CBMA’s potential to improve the quality of cartilage repair tissue following BMS has been reported in both in vivo models and a clinical study. In an equine model, Foriter et al.¹² reported that when added during BMS, CBMA improved healing compared with BMS alone based on histological and radiological parameters. In a goat model, Saw et al.⁶⁶ described that BMS in combination with CBMA and HA showed significantly improved healing compared with BMS with HA only. In addition, the authors reported that nearly complete coverage of the defect and evidence of hyaline cartilage repair were found in the CBMA-treated group. In a clinical study, Hannon et al.⁶⁷ performed a retrospective comparative study of 22 OLT patients treated with BMS alone or BMS with concomitant CBMA. The authors reported that BMS with CBMA resulted in comparably good medium-term functional outcomes, but improved border repair tissue and less evidence of fissuring and fibrillation on MRI compared with BMS alone.

A single report on CBMA in OLT patients treated with AOT has been published (LOE: IV).³⁶ This showed significant improvement of clinical outcome in 72 patients at a mean follow-up of 28 months. In addition, the authors reported that magnetic resonance imaging using T2 mapping showed restoration of radius curvature and color stratification similar to that of native cartilage.

Based on current evidence, it appears that CBMA can improve cartilage repair in OLT. However, further conclusions cannot be made at this early juncture and further research, including comparative studies, is warranted.

Scaffold-Based Therapy

Scaffold-based therapy is another reparative option for treatment of OLT that has recently been gaining support by clinical evidence.

Matrix-induced autologous chondrocyte implantation (MACI) consists of a 2-stage operative procedure. In the first stage, autologous chondrocytes are obtained by biopsy and cultured ex vivo for several weeks. In the second stage, the chondrocytes are seeded in a scaffold containing type I/III collagen, hyaluronan, and polyglycolic/polylactic acid and implanted in the site of the defect.^2,68,69 MACI has shown promising functional outcomes in the literature, with the majority of patients achieving good to excellent results. To our knowledge, the longest follow-up after MACI was reported by Giannini et al.⁷⁰ following 46 ankles for a mean of 87.2 months (LOE: IV). The authors reported that the mean score for AOFS was 92 out of 100 points.

Autologous matrix-induced chondrogenesis (AMIC) is a 1-step scaffold-based therapy. In this procedure, an acellular collagen I/III matrix is used to cover the lesion following BMS. AMIC attempts to stabilize the blood clot and stimulate chondrogenesis from MSCs. Wiewiorski et al.⁷¹ (LOE: IV) investigated the outcomes of 23 OLT patients following AMIC at a median of 23 months postoperatively and reported an increase in median AOFAS scores from 60.3 to 90.9. Recently, Valderrabano et al.⁷² (LOE: IV) reported a mean AOFAS score increase from 60 to 89 in patients who received AMIC. They also reported that 84% of studied patients had normal or near-normal signal intensity of the repair tissue compared with the adjacent native cartilage.

Bone marrow–derived cells transplantation (BMDCT), a combination of CBMA and scaffold material, is used to fill the defect site. Several clinical articles have shown that postoperative clinical scores improved significantly using this treatment modality.^73-79

Overview

Biologic therapy to improve OLT outcomes remains a subject of debate. Based on currently available basic and clinical evidence, biologic agents and scaffold-based therapies have been shown to improve clinical and radiological outcomes in OLT. Nevertheless, variable production methods of these biologic augmentations confound the interpretation of clinical outcomes. A recent systematic review showed that most studies assessing clinical outcomes following operative treatment in OLT are of low levels of evidence and of poor methodological quality.⁸⁰ As such, well-designed clinical trials with patient-specific, validated and objective outcome measurements are warranted to develop standardized clinical guidelines for the use of biologic augmentations for treatment of OLT in clinical practice.

Footnotes

Acknowledgments and Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: John G. Kennedy is a consultant for Arteriocyte, Inc; received research support from the Ohnell Family Foundation, Mr. and Mrs. Michael J Levitt, Arteriocyte Inc; is a board member for the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), International Society for Cartilage Repair of the Ankle (ISCRA), American Orthopaedic Foot & Ankle Society (AOFAS) Awards and Scholarships Committee, International Cartilage Repair Society (ICRS) finance board.

References

Guillo

Bauer

Lee

Takao

Kong

Stone

. Consensus in chronic ankle instability: aetiology, assessment, surgical indications and place for arthroscopy. Orthop Traumatol Surg Res. 2013;99(8 Suppl):S411-9. doi:10.1016/j.otsr.2013.10.009.

Zengerink

Struijs

Tol

van Dijk

CN.

Treatment of osteochondral lesions of the talus: a systematic review. Knee Surg Sports Traumatol Arthrosc. 2010;18(2):238-46.

Robinson

Winson

Harries

Kelly

AJ.

Arthroscopic treatment of osteochondral lesions of the talus. J Bone Joint Surg Br. 2003;85(7):989-93.

Ferkel

Zanotti

Komenda

Sgaglione

Cheng

Applegate

. Arthroscopic treatment of chronic osteochondral lesions of the talus: long-term results. Am J Sports Med. 2008;36(9):1750-62.

Lee

Bai

Yoon

Jung

Seon

JK.

Second-look arthroscopic findings and clinical outcomes after microfracture for osteochondral lesions of the talus. Am J Sports Med. 2009;37(1):63S-70S.

Becher

Driessen

Hess

Longo

Maffulli

Thermann

Microfracture for chondral defects of the talus: maintenance of early results at midterm follow-up. Knee Surg Sports Traumatol Arthrosc. 2010:18(5);656-63.

Chuckpaiwong

Berkson

Theodore

GH.

Microfracture for osteochondral lesions of the ankle: outcome analysis and outcome predictors of 105 cases. Arthroscopy. 2008;24(1):106-12. doi:10.1016/j.arthro.2007.07.022.

Choi

Park

Kim

Lee

JW.

Osteochondral lesion of the talus: is there a critical defect size for poor outcome?

Am J Sports Med. 2009;37(10):1974-80. doi:10.1177/0363546509335765.

Choi

Kim

Lee

JW.

Prognostic significance of the containment and location of osteochondral lesions of the talus: independent adverse outcomes associated with uncontained lesions of the talar shoulder. Am J Sports Med. 2013;41(1):126-33. doi:10.1177/036354651245330.

10.

Lieberthal

Sambamurthy

Scanzello

CR.

Inflammation in joint injury and post-traumatic osteoarthritis. Osteoarthritis Cartilage. 2015;23(11):1825-34. doi:10.1016/j.joca.2015.08.015.

11.

Smyth

Murawski

Fortier

Cole

Kennedy

JG.

Platelet-rich plasma in the pathologic processes of cartilage: review of basic science evidence. Arthroscopy. 2013;29(8):1399-409. doi:10.1016/j.arthro.2013.03.004.

12.

Fortier

Potter

Rickey

Schnabel

Foo

Chong

. Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am. 2010;92-A:1927-37.

13.

Freed

Marquis

Nohria

Emmanual

Mikos

Langer

Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers. J Biomed Mater Res. 1993;27(1):11-23.

14.

van Susante

Buma

van Osch

Versleyen

van

der

Kraan

van

der

Berg

. Culture of chondrocytes in alginate and collagen carrier gels. Acta Orthop Scand. 1995;66(6):549-56.

15.

Grigolo

Lisignoli

Piacentini

Fiorini

Gobbi

Mazzotti

. Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAff 11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials. 2002;23(4):1187-95.

16.

Takao

Uchio

Kakimaru

Kumahashi

Ochi

Arthroscopic drilling with debridement of remaining cartilage for osteochondral lesions of the talar dome in unstable ankles. Am J Sports Med. 2004;32(2):332-6.

17.

Murawski

Kennedy

JG.

Operative treatment of osteochondral lesions of the talus. J Bone Joint Surg Am. 2013;95(11):1045-54. doi:10.2106/JBJS.L.00773.

18.

Tol

Struijs

Bossuyt

Verhagen

van Dijk

CN.

Treatment strategies in osteochondral defects of the talar dome: a systematic review. Foot Ankle Int. 2000;21(2):119-26.

19.

Verhagen

Struijs

Bossuyt

van Dijk

CN.

Systematic review of treatment strategies for osteochondral defects of the talar dome. Foot Ankle Clin. 2003;8(2):233-42.

20.

van Bergen

Kox

Maas

Sierevelt

Kerkhoffs

van Dijk

CN.

Arthroscopic treatment of osteochondral defects of the talus: outcomes at eight to twenty years of follow-up. J Bone Joint Surg Am. 2013;95(6):519-25. doi:10.2106/JBJS.L.00675.

21.

Saxena

Eakin

Articular talar injuries in athletes: results of microfracture and autogenous bone graft. Am J Sports Med. 2007;35(10):1680-7.

22.

van Bergen

Kox

Maas

Sierevelt

Kerkhoffs

van Dijk

CN.

Arthroscopic treatment of osteochondral defects of the talus: outcomes at eight to twenty years of follow-up. J Bone Joint Surg Am. 2013;95(6):519-25. doi:10.2106/JBJS.L.00675.

23.

Seijas

Alvarez

Ares

Steinbacher

Cuscó

Cugat

Osteocartilaginous lesions of the talus in soccer players. Arch Orthop Trauma Surg. 2010;130(3):329-33. doi:10.1007/s00402-008-0783-7.

24.

Buckwalter

Mow

Ratcliffe

Restoration of injured or degenerated articular cartilage. J Am Acad Orthop Surg. 1994;2(4):192-201.

25.

Nehrer

Spector

Minas

Histologic analysis of tissue after failed cartilage repair procedures. Clin Orthop Relat Res. 1999;(365):149-62.

26.

Duncan

Jundt

Riddle

Pitchford

Christopherson

The tibial subchondral plate. A scanning electron microscopic study. J Bone Joint Surg Am. 1987;69(8):1212-20.

27.

Pugh

Radin

Rose

RM.

Quantitative studies of human subchondral cancellous bone. Its relationship to the state of its overlying cartilage. J Bone Joint Surg Am. 1974;56(2):313-21.

28.

Mankin

HJ.

The response of articular cartilage to mechanical injury. J Bone Joint Surg Am. 1982;64(3):460-6.

29.

Jackson

Lalor

Aberman

Simon

TM.

Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study. J Bone Joint Surg Am. 2001;83-A(1):53-64.

30.

Shapiro

Koide

Glimcher

MJ.

Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1993;75(4):532-53.

31.

Cuttica

Shockley

Hyer

Berlet

GC.

Correlation of MRI edema and clinical outcomes following microfracture of osteochondral lesions of the talus. Foot Ankle Spec. 2011;4(5):274-9. doi:10.1177/1938640011411082.

32.

Adams

Jr Nettles

Jones

Miller

Guyton

Schon

LC.

Inflammatory cytokines and cellular metabolites as synovial fluid biomarkers of posttraumatic ankle arthritis. Foot Ankle Int. 2014;35(12):1241-9. doi:10.1177/1071100714550652.

33.

Adams

Setton

Bell

Easley

Huebner

Stabler

. Inflammatory cytokines and matrix metalloproteinases in the synovial fluid after intra-articular ankle fracture. Foot Ankle Int. 2015;36(11):1264-71. doi:10.1177/1071100715611176.

34.

Huebner

Shrive

Frank

CB.

New surgical model of post-traumatic osteoarthritis: isolated intra-articular bone injury in the rabbit. J Orthop Res 2013;31:914-20.

35.

Huebner

Shrive

Frank

CB.

Dexamethasone inhibits inflammation and cartilage damage in a new model of posttraumatic osteoarthritis. J Orthop Res 2014;32:566-72.

36.

Kennedy

Murawsk

The treatment of osteochondral lesions of the talus with autologous osteochondral transplantation and bone marrow aspirate concentrate: surgical technique. Cartilage. 2011;2(4):327-36.

37.

Hangody

Dobos

Balo

Panics

Hangody

Berkes

Clinical experiences with autologous osteochondral mosaicplasty in an athletic population: a 17-year prospective multicenter study. Am J Sports Med. 2010;38(6):1125-33.

38.

Scranton

Jr Frey

Feder

KS.

Outcome of osteochondral autograft transplantation for type-V cystic osteochondral lesions of the talus. J Bone Joint Surg Br. 2006;88(5):614-9.

39.

Woelfle

Reichel

Javaheripour-Otto

Nelitz

Clinical outcome and magnetic resonance imaging after osteochondral autologous transplantation in osteochondritis dissecans of the talus. Foot Ankle Int. 2013;34(2):173-9.

40.

Paul

Sagstetter

Lämmle

Spang

El-Azab

Imhoff

. Sports activity after osteochondral transplantation of the talus. Am J Sports Med. 2012;40(4):870-4.

41.

Fraser

Harris

Prado

Kennedy

JG.

Autologous osteochondral transplantation for osteochondral lesions of the talus in an athletic population. Knee Surg Sports Traumatol Arthrosc. 2016;24(4):1272-9. doi:10.1007/s00167-015-3606-8.

42.

Siebert

Miltner

Weber

Sopka

Koch

Niedhart

Healing of osteochondral grafts in an ovine model under the influence of bFGF. Arthroscopy. 2003;19(2):182-7.

43.

Tibesku

Daniilidis

Szuwart

Jahn

Schlegel

Fuchs-Winkelmann

Influence of hepatocyte growth factor on autologous osteochondral transplants in an animal model. Arch Orthop Trauma Surg. 2011;131(8):1145-51.

44.

Gulotta

Rudzki

Kovacevic

Chen

Milentijevic

Williams

3rd . Chondrocyte death and cartilage degradation after autologous osteochondral transplantation surgery in a rabbit model. Am J Sports Med. 2009;37(7):1324-33. doi:10.1177/0363546509333476.

45.

Valderrabano

Leumann

Rasch

Egelhof

Hintermann

Pagenstert

Knee-to-ankle mosaicplasty for the treatment of osteochondral lesions of the ankle joint. Am J Sports Med. 2009;37(Suppl 1):105S-11S.

46.

Lamb

Murawski

Deyer

Kennedy

JG.

Chevron-type medial malleolar osteotomy: a functional, radiographic and quantitative T2-mapping MRI analysis. Knee Surg Sports Traumatol Arthrosc. 2013;21(6):1283-8. doi:10.1007/s00167-012-2050-2.

47.

Fansa

Murawski

Imhauser

Nguyen

Kennedy

JG.

Autologous osteochondral transplantation of the talus partially restores contact mechanics of the ankle joint. Am J Sports Med. 2011;39(11):2457-65. doi:10.1177/0363546511419811.

48.

Baums

Schultz

Kostuj

Klinger

HM.

Cartilage repair techniques of the talus: an update. World J Orthop. 2014;5(3):171-9. doi:10.5312/wjo.v5.i3.171.

49.

Chubinskaya

Huch

Mikecz

Cs-Szabo

Hasty

Kuettner

. Chondrocyte matrix metalloproteinase-8: up-regulation of neutrophil collagenase by interleukin-1β in human cartilage from knee and ankle joints. Lab Invest. 1996;74(1):232-40.

50.

Boswell

Cole

Sundman

Karas

Fortier

LA.

Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy. 2012;28(3):429-39. doi:10.1016/j.arthro.2011.10.018.

51.

Holmes

Wilson

Silverberg

Goerger

Fortier

LA.

Identification of the optimal biologic to enhance endogenous stem cell recruitment. Paper presented at: ORS 2014 Annual Meeting; March 15-18, 2014; New Orleans, LA.

52.

Sundman

Cole

Fortier

LA.

Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39(10):2135-40. doi:10.1177/0363546511417792.

53.

Davis

Abukabda

Radio

Witt-Enderby

Clafshenkel

Cairone

. Platelet-rich preparations to improve healing. Part II: platelet activation and enrichment, leukocyte inclusion, and other selection criteria. J Oral Implantol. 2014;40(4):511-21. doi:10.1563/AAID-JOI-D-12-00106.

54.

Smyth

Haleem

Murawski

Deland

Kennedy

JG.

The effect of platelet-rich plasma on autologous osteochondral transplantation: an in vivo rabbit model. J Bone Joint Surg Am. 2013;95(24):2185-93. doi:10.2106/JBJS.L.01497.

55.

Boakye

Ross

Pinski

Smyth

Haleem

Hannon

. Platelet-rich plasma increases transforming growth factor-β1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model. World J Orthop. 2015;6(11):961-9. doi:10.5312/wjo.v6.i11.961.

56.

Raeissadat

Rayegani

Hassanabadi

Fathi

Ghorbani

Babaee

. Knee osteoarthritis injection choices: platelet- rich plasma (PRP) versus hyaluronic acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015;8:1-8.

57.

Rayegani

Raeissadat

Taheri

Babaee

Bahrami

Eliaspour

. Does intra articular platelet rich plasma injection improve function, pain and quality of life in patients with osteoarthritis of the knee? A randomized clinical trial. Orthop Rev (Pavia). 2014;6(3):5405.

58.

Battaglia

Guaraldi

Vannini

Rossi

Timoncini

Buda

. Efficacy of ultrasound-guided intra-articular injections of platelet-rich plasma versus hyaluronic acid for hip osteoarthritis. Orthopedics. 2013;36(12):e1501-8.

59.

Manunta

Manconi

The treatment of chondral lesions of the knee with the microfracture technique and platelet-rich plasma. Joints. 2014;1(4):167-70.

60.

Patel

Dhillon

Aggarwal

Marwaha

Jain

Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356-64.

61.

Filardo

Kon

Di Martino

Di Matteo

Merli

Cenacchi

. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord. 2012;13:229.

62.

Cerza

Carnì

Carcangiu

Di Vavo

Schiavilla

Pecora

, and others. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012;40(12):2822-7.

63.

Mei-Dan

Carmont

Laver

Mann

Maffulli

Nyska

Platelet-rich plasma or hyaluronate in the management of osteochondral lesions of the talus. Am J Sports Med. 2012;40:534-41.

64.

Guney

Akar

Karaman

Oner

Guney

Clinical outcomes of platelet rich plasma (PRP) as an adjunct to microfracture surgery in osteochondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc. 2015;23(8):2384-9. doi:10.1007/s00167-013-2784-5.

65.

Görmeli

Karakaplan

Görmeli

Sarıkaya

Elmalı

Ersoy

Clinical effects of platelet-rich plasma and hyaluronic acid as an additional therapy for talar osteochondral lesions treated with microfracture surgery: a prospective randomized clinical trial. Foot Ankle Int. 2015;36(8):891-900. doi:10.1177/1071100715578435.

66.

Saw

Hussin

Loke

Azam

Chen

Tay

. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: an experimental study in a goat model. Arthroscopy. 2009;25(12):1391-400. doi:10.1016/j.arthro.2009.07.011.

67.

Hannon

Ross

Murawski

Deyer

Smyth

Hogan

. Arthroscopic bone marrow stimulation and concentrated bone marrow aspirate for osteochondral lesions of the talus: a case-control study of functional and magnetic resonance observation of cartilage repair tissue outcomes. Arthroscopy. 2016;32(2):339-47. doi:10.1016/j.arthro.2015.07.012.

68.

Giza

Sullivan

Ocel

Lundeen

Mitchell

Veris

. Matrix-induced autologous chondrocyte implantation of talus articular defects. Foot Ankle Int. 2010;31:747-53.

69.

Schneider

Karaikudi

Matrix-induced autologous chondrocyte implantation (MACI) grafting for osteochondral lesions of the talus. Foot Ankle Int 2009;30:810-4.

70.

Giannini

Buda

Ruffilli

Cavallo

Pagliazzi

Bulzamini

. Arthroscopic autologous chondrocyte implantation in the ankle joint. Knee Surg Sports Traumatol Arthrosc. 2014;22(6):1311-9. doi:10.1007/s00167-013-2640-7.

71.

Wiewiorski

Miska

Kretzschmar

Studler

Bieri

Valderrabano

Delayed gadolinium-enhanced MRI of cartilage of the ankle joint: results after autologous matrix-induced chondrogenesis (AMIC)-aided reconstruction of osteochondral lesions of the talus. Clin Radiol. 2013;68(10):1031-8. doi:10.1016/j.crad.2013.04.016.

72.

Valderrabano

Miska

Leumann

Wiewiorski

Reconstruction of osteochondral lesions of the talus with autologous spongiosa grafts and autologous matrix-induced chondrogenesis. Am J Sports Med. 2013;41(3):519-27. doi:10.1177/0363546513476671.

73.

Giannini

Buda

Vannini

Cavallo

Grigolo

One-step bone marrow-derived cell transplantation in talar osteochondral lesions. Clin Orthop Relat Res. 2009;467(12):3307-20. doi:10.1007/s11999-009-0885-8.

74.

Giannini

Buda

Cavallo

Ruffilli

Cenacchi

Cavallo

. Cartilage repair evolution in post-traumatic osteochondral lesions of the talus: from open field autologous chondrocyte to bone-marrow-derived cells transplantation. Injury. 2010;41(11):1196-203. doi:10.1016/j.injury.2010.09.028.

75.

Battaglia

Rimondi

Monti

Guaraldi

Sant’Andrea

Buda

. Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle. Eur J Radiol. 2011;80(2):e132-9. doi:10.1016/j.ejrad.2010.08.008.

76.

Giannini

Buda

Battaglia

Cavallo

Ruffilli

Ramponi

. One-step repair in talar osteochondral lesions: 4-year clinical results and t2-mapping capability in outcome prediction. Am J Sports Med. 2013;41(3):511-8. doi:10.1177/0363546512467622.

77.

Buda

Vannini

Cavallo

Baldassarri

Natali

Castagnini

. One-step bone marrow-derived cell transplantation in talarosteochondral lesions: mid-term results. Joints. 2014;1(3):102-7.

78.

Cadossi

Buda

Ramponi

Sambri

Natali

Giannini

Bone marrow-derived cells and biophysical stimulation for talar osteochondral lesions: a randomized controlled study. Foot Ankle Int. 2014;35(10):981-7. doi:10.1177/1071100714539660.

79.

Buda

Vannini

Castagnini

Cavallo

Ruffilli

Ramponi

. Regenerative treatment in osteochondral lesions of the talus: autologous chondrocyte implantation versus one-step bone marrow derived cells transplantation. Int Orthop. 2015;39(5):893-900. doi:10.1007/s00264-015-2685-y.

80.

Pinski

Boakye

Murawski

Hannon

Ross

Kennedy

JG.

Low level of evidence and methodologic quality of clinical outcome studies on cartilage repair of the ankle. Arthroscopy. 2016;32(1):214-222.e1. doi:10.1016/j.arthro.2015.06.050.

Operative Treatment for Osteochondral Lesions of the Talus

Abstract

Objective

Design

Results

Conclusions

Keywords

Introduction

Surgical Treament Modalities of OLT

Bone Marrow Stimulation

Autologous Osteochondral Transplantation

Biologic Augmentation for Cartilage Repair

Platelet-Rich Plasma

Concentrated Bone Marrow Aspirate

Scaffold-Based Therapy

Overview

Footnotes

Acknowledgments and Funding

Declaration of Conflicting Interests

References