Tissue Engineering and Regenerative Medicine Strategies in Meniscus Lesions.

Arthroscopy. 2011 Oct 

Pereira H, Frias AM, Oliveira JM, Espregueira-Mendes J, Reis RL.

Abstract

PURPOSE:

The aim of this systematic review was to address tissue engineering and regenerative medicine (TERM) strategies applied to the meniscus, specifically (1) clinical applications, indications, results, and pitfalls and (2) the main trends in research assessed by evaluation of preclinical (in vivo) studies.

METHODS:

Three independent reviewers performed a search on PubMed, from 2006 to March 31, 2011, using the term "meniscus" with all of the following terms: "scaffolds," "constructs," "cells," "growth factors," "implant," "tissue engineering," and "regenerative medicine." Inclusion criteria were English language-written, original clinical research (Level of Evidence I to IV) and preclinical studies of TERM application in knee meniscal lesions. Reference lists and related articles on journal Web sites of selected articles were checked until prepublication for potential studies that could not be identified eventually by our original search. The modified Coleman Methodology score was used for study quality analysis of clinical trials.

RESULTS:

The PubMed search identified 286 articles (a similar search from 2000 to 2005 identified 161 articles). Non-English-language articles (n = 9), Level V publications (n = 19), in vitro studies (n = 118), and 102 studies not related to the topic were excluded. One reference was identified outside of PubMed. Thirty-eight references that met the inclusion criteria were identified from the original search. On the basis of our prepublication search, 2 other references were included. A total of 9 clinical and 31 preclinical studies were selected for further analysis. Of the clinical trials, 1 was classified as Level I, 2 as Level II, and 6 as Level IV. Eight referred to acellular scaffold implantation for partial meniscal replacement, and one comprised fibrin clot application. The mean modified Coleman Methodology score was 48.0 (SD, 15.7). Of the preclinical studies, 11 original works reported on studies using large animal models whereas 20 research studies used small animals. In these studies the experimental design favored cell-seeded scaffolds or scaffolds enhanced with growth factors (GFs) in attempts to improve tissue healing, as opposed to the plain acellular scaffolds that were predominant in clinical trials. Injection of mesenchymal stem cells and gene therapy are also presented as alternative strategies.

CONCLUSIONS:

Partial meniscal substitution using acellular scaffolds in selected patients with irreparable loss of tissue may be a safe and promising procedure. However, there is only 1 randomized controlled study supporting its application, and globally, many methodologic issues of published trials limit further conclusions. We registered a different trend in preclinical trials, with most considering augmentation of scaffolds by cells and/or GFs, as opposed to the predominantly acellular approach in clinical trials. Different TERM approaches to enhance meniscal repair or regeneration are in preclinical analysis, such as the use of mesenchymal stem cells, gene therapy, and GFs alone or in combination, and thus could be considered in the design of subsequent trials.

LEVEL OF EVIDENCE:

Level IV, systematic review of Level I to IV studies.

IORG Sports Medicine Update

Platelet-Rich Plasma Intra-Articular Injection Versus Hyaluronic Acid Viscosupplementation as Treatments for Cartilage Pathology: From Early Degeneration to Osteoarthritis.

Arthroscopy. 2011 Aug 8

Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari PM, Giannini S, Marcacci M.

Source

Biomechanics Laboratory-III Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy.

Abstract

PURPOSE:

The aim of our study is to compare the efficacy of platelet-rich plasma (PRP) and viscosupplementation (hyaluronic acid [HA]) intra-articular injections for the treatment of knee cartilage degenerative lesions and osteoarthritis (OA).

METHODS:

The study involved 150 patients affected by cartilage degenerative lesions and early and severe OA. Fifty symptomatic patients were treated with 3 autologous PRP intra-articular injections and were evaluated prospectively at enrollment and at 2- and 6-month follow-up. The results obtained were compared with 2 homogeneous groups of patients treated with HA injections. One group was treated with injections of high-molecular weight HA; the other group was treated with low-molecular weight (LW) HA. International Knee Documentation Committee and EQ VAS scores were used for clinical evaluation; adverse events and patient satisfaction were also recorded.

RESULTS:

At 2 months' follow-up, the PRP and LW HA groups showed a similar improvement, with higher results compared with the high-molecular weight HA group (P < .005). At 6 months' follow-up, better results were observed in the PRP group (P < .005). PRP and LW HA treatments offered similar results in patients aged over 50 years and in the treatment of advanced OA. PRP showed a better performance compared with HA in younger patients affected by cartilage lesions or early OA.

CONCLUSIONS:

Autologous PRP injections showed more and longer efficacy than HA injections in reducing pain and symptoms and recovering articular function. Better results were achieved in younger and more active patients with a low degree of cartilage degeneration, whereas a worse outcome was obtained in more degenerated joints and in older patients, in whom results similar to those of viscosupplementation have been observed.

LEVEL OF EVIDENCE:

Level II, prospective comparative study.

IORG Sports medicine update

Single bundle anterior cruciate reconstruction does not restore normal knee kinematics at six months: An upright MRI study.

J Bone Joint Surg Br. 2011 Oct;93(10):1334-40.
Nicholson JA, Sutherland AG, Smith FW.


Abnormal knee kinematics following reconstruction of the anterior cruciate ligament may exist despite an apparent resolution of tibial laxity and functional benefit.
 We performed upright, weight-bearing MR scans of both knees in the sagittal plane at different angles of flexion to determine the kinematics of the knee following unilateral reconstruction (n = 12). The uninjured knee acted as a control. Scans were performed pre-operatively and at three and six months post-operatively. Anteroposterior tibial laxity was determined using an arthrometer and patient function by validated questionnaires before and after reconstruction. In all the knees with deficient anterior cruciate ligaments, the tibial plateau was displaced anteriorly and internally rotated relative to the femur when compared with the control contralateral knee, particularly in extension and early flexion (mean lateral compartment displacement: extension 7.9 mm (sd 4.8), p = 0.002 and 30° flexion 5.1 mm (sd 3.6), p = 0.004). In all ten patients underwent post-operative scans. Reconstruction reduced the subluxation of the lateral tibial plateau at three months, with resolution of anterior displacement in early flexion, but not in extension (p = 0.015). At six months, the reconstructed knee again showed anterior subluxation in both the lateral (mean: extension 4.2 mm (sd 4.2), p = 0.021 and 30° flexion 3.2 mm (sd 3.3), p = 0.024) and medial compartments (extension, p = 0.049). 
Our results show that despite improvement in laxity and functional benefit, abnormal knee kinematics remain at six months and actually deteriorate from three to six months following reconstruction of the anterior cruciate ligament.


IORG Sports Medicine Update 24th - 30th OCT 2011

ACL avulsion fractures in children. Part I- Overview

Short review series
ACL avulsion fractures in children. Part I- Overview
Series Author – Dr AK Shyam MS Orth

Introduction:
These injuries were first described by Poncet in 1875 [1]. In adults the anterior cruciate ligament directly inserts on the tibia bone [2]. However in children a sleeve of perichondrium connects the ligament to the epiphyseal cartilage, thus making this as the weakest part of the link. The ACL avulsion injuries are generally secondary to either bicycle or other sports injuries and are commonly seen between 6 to 15 years of age [3]. Most commonly the ACL is avulsed distally from the proximal tibial eminence. Avulsion from femur and simultaneous avulsions from both sites are also reported [4,5,6]. These injuries may be associated with other ligament injuries and especially meniscal injuries [7,8].

Classification:
Myers and McKeever classified this avulsion fracture by degree of displacement [9]:
Type I: minimally displaced, with only slight elevation of the anterior margin;
Type II: hinged posteriorly, producing a beak-like appearance on the lateral radiograph;
Type III: completely displaced and elevated from its bed.
Type III fractures may be further classified. IIIa fractures are displaced but not rotated and IIIb fractures are displaced and rotated.

Commonly the fractures are of type II or III.

The radiographs underestimate the size of the fragment due to presence of radiolucent cartilage [similar to as seen in lateral condyle humerus fracture]

Mechanism of injury: valgus stress on flexed knee or hyperextension

Management options:

Type I injuries – conservative management with cylinder cast in 20⁰ flexion (position of relaxed ACL) [10,11]

Type II injuries – Reduce by extension and pressure on the lateral femoral condyle and if reduced are immobilized with cast in extension [12,13]. The reduction can be facilitated by joint aspiration. Few authors immobilize the limb in flexion for a similar reason of decreasing the tension on ACL.
There are several difficulties associated with arthroscopic reduction of type II and III fractures including potential meniscal entrapment, nonreduction of the fracture site, and bowstringing of the fragment between ACL and anterior meniscus and laxity of the ACL tissue after repair [12,14]
An unreduced type II fracture should be treated as displaced type III

Type III fracture – closed reduction and arthroscopic fixation is current gold standard. Two different modalities like screw fixation and non screw fixation eg wire loop, absorbable sutures, suture anchors etc are used and will be elaborated in following parts of this review series.

Next in this series – ACL avulsion injuries treated with Sutures – Evidence for advantages and disadvantages

1. Burstein DB, Viola A, Fulkerson JP. Entrapment ofthe medial meniscus in a fracture of the tibial eminence. Arthroscopv 1988 ; 4 :47


2. Matz SO, Jackson DW. Anterior cruciate ligament injury in children. Am J Knee Surg,1988;1:59.

3. Nichols JN, Tehranzadeh J. A review of the tibial spine fractures in bicycle injury. Am J Sports Med, 1987;15:172.

4. Eady JL, Cardenas CD, Sopa D. Avulsion of the femoral attachment of the anterior cruciate ligament in a seven-year-old child. J Bone Joint Surg Am, 1982;64:1376.

5. Robinson SC, Driscoll SE. Simultaneous osteochondral avulsion of the femoral and tibial insertions of the anterior cruciate ligament. J Bone Joint Surg Am, 1981;63:1342.

6. Marina VR, Taco G, Jacob C, Diederik G. Femoral avulsion fracture of the anterior cruciate ligament in an 11-year-old girl. Injury Extra (2006) 37, 129—132

7. Chandler JT, Miller TK. Tibial eminence fracture with meniscal entrapment. Arthroscopy. 1995 Aug;11(4):499-502.

8. Kocher MS, Micheli LJ, Gerbino P, Hresko MT. Tibial eminence fractures in children: prevalence of meniscal entrapment. Am J Sports Med. 2003 May-Jun;31(3):404-7.

9. Meyers MH, McKeever FM. Fracture of the intercondylar eminence of the tibia. J Bone Jt Surg Am 1970;52A: 1677–84.

10. Oostvogel HJM, Klasen HJ, Reddingius RE. Fractures of the intercondylar eminence in children and adults. Arch Orthop Trauma Surg. 1988;107:202–247.

11. van Loon T, Marti RK. A fracture of the intercondylar eminence of the tibia treated by arthroscopic fixation. Arthroscopy. 1991;7:385–388.

12. Lowe J, Chaimsky G, Freedman A, Zion I, Howard C. The anatomy of tibial eminence fractures: arthroscopic observations following failed closed reduction. J Bone Joint Surg Am. 2002 Nov;84-A(11):1933-8.

13.Moran M, Macnicol MF. II Paediatric epiphyseal fractures around the knee. Curr Orthop 2006;20(4):256–265.

14. Siparsky PN, Kocher MS. Current concepts in pediatric and adolescent arthroscopy. Arthroscopy. 2009 Dec;25(12):1453-69.

ACL Tear – To Operate or Not To Operate

ACL Tear – To Operate or Not To Operate

PREVIEW
ACL reconstruction is one of the most commonly done surgeries in field of sports medicine. In past several authors have reported that non-operative treatment of a rupture of the anterior cruciate ligament, with coordinated rehabilitation and modification of activity, resulted in satisfactory function [1,2]. Others have been convinced that an operation is necessary to avoid progressively worse function of the knee [3,4]. We here will analyze the evidence for recommendation of this surgery.

INTRODUCTION
ACL disruption is been associated with increased incidence of arthrosis of the knee is a fact that is backed up by enough evidence [5,6], however controversy still exists whether ACL reconstruction reduces this arthrosis incidence and a great clinical divide seems to exist among the surgeons. A recent survey of American academy of orthopedic surgeons [2003] suggests that this disagreement may be multifactorial [7]. A lack of adequate peer-reviewed literature, controversy among the available scientific publications, inadequate information dissemination, the preference to rely on clinical experience, or a combination of these factors may lead to such clinical disagreement.

LITERATURE REVIEW
Kessler et al [2008]retrospectively analysed 109 patients with mean of 11.4 years follow up comparing the conservative and surgical management of ACL tear [8]. Comparison of the groups based on the IKDC criteria showed a clear advantage in favor of ACL reconstruction. Nevertheless, it must be remembered that the overall IKDC score is determined by the worst individual parameter. Therefore, it is not a surprise to find that patients without ACL have greater anteroposterior translation and achieve lower IKDC scores. Even though surgical procedures might be preferred on the basis of these results, a large proportion of the patients with distinct, objective anteroposterior instability were subjectively almost symptom-free and have high level of activity. A very unique finding of this study is significantly lower rate of osteoarthritis in patient group after conservative treatment as compared to surgically reconstructed group (42% vs. 25%). Thus conservatively treated patients had better results with respect to long term osteoarthritis.
Casteleyn and Handelberg [1996]were of the opinion that if physical activity is kept to minimum and pivotal sports activities are avoided, then the situation may remain stable for many years [9].
Kostogiannis et al [2007] prospectively observed 100 patients with an acute total ACL injury without reconstruction for 15 years and concluded that early modification of activity and neuromuscular rehabilitation resulted in good knee function and an acceptable activity level in the majority of patients [10].
On the other hand, Strehl and Eggli [2007], in their investigation of conservative treatment for ACL rupture found that almost two-thirds of those patients selected for primary conservative treatment required surgical reconstruction in the long-term [11]. However most of the patients included wished to continue with high demand activity and demanded surgery in their series.
Daniel et al [1994] showed that ACL reconstruction does not always yield improved outcomes compared to the natural history and pointed out that patients who were able to “cope” with ACL deficiency may actually have better outcomes in some respects than do patients who have reconstruction [12].
The Cochrane database analysis of 2005 scrutinized two randomized studies [13], one by Sandberg et al [14] and another by Anderson et al [15]. Sandberg et al concluded that surgery of the anterior cruciate ligament produces a somewhat more stable knee joint, at least for the first few years, whereas non-operative treatment has the advantage that muscle power, range of motion, and function are regained more rapidly. The recovery of function is similar for the two regimens and for most purposes is satisfactory, but patients who have a lesion of the anterior cruciate ligament. Anderson et al concluded that repair and augmentation of the anterior Cruciate ligament resulted in better function of the knee at a higher level of activity than did simple repair or repair of only the peripheral lesions. The patients who had augmented repair had better stability in the sagittal plane, even though the restored stability was not equivalent to that of the uninjured knee. The database analyst however concluded that there was insufficient evidence to determine the relative effects of the surgical versus non-surgical treatment interventions performed in the early 1980s. However, there was some evidence that conservative treatment of acute ACL injuries can result in a satisfactory outcome.

RECENT STUDIES
Meuffels et al [2009] presented their results of 10 years follow-up of ACL tear in highly active individuals treated operatively versus non-operatively [16]. They concluded that the instability repair using a bone-patella-tendon-bone anterior cruciate ligament reconstruction is a good knee stabilizing operation. Both treatment options however show similar patient outcome at 10 year follow up.
Meunier et al [2007] investigated the long-term outcome of 100 patients 15 years after having been randomly allocated to primary repair (augmented or non-augmented) or non-surgical treatment of an anterior cruciate ligament (ACL) rupture [17]. The subjective outcome was similar between the groups, with no difference regarding activity level and knee-injury and osteoarthritis outcome score but with a slightly lower Lysholm score for the non-surgically treated group. This difference was attributed to more instability symptoms. The radiological osteoarthritis (OA) frequency did not differ between surgically or non-surgically treated patients, but if a meniscectomy was performed, two-thirds of the patients showed OA changes regardless of initial treatment of the ACL. There were significantly more meniscus injuries in patients initially treated non-surgically. Early ACL repair and also ACL reconstruction can reduce the risk of secondary meniscus tears which indirectly will decrease the incidence of osteoarthrosis
Fithian et al [2005] performed a prospective nonrandomized controlled trial to study the surgical risk factors that can be used to indicate whether reconstruction or conservative management is best for an individual patient [18]. Patients were classified as high, moderate, or low risk using preinjury sports participation and knee laxity measurements. Early phase conservative management resulted in more late phase meniscus surgery than did early phase reconstruction at all risk levels. Early- and late-reconstruction patients' Tegner scores increased from presurgery to follow-up but did not return to preinjury levels. Early-reconstruction patients had higher rates of degenerative change on radiographs than did nonreconstruction patients. They concluded that early phase reconstruction reduces the late phase knee laxity, risk of symptomatic instability, and the risk of late meniscus tear and surgery. Moderate- and high-risk patients had similar rates of late phase injury and surgery. Reconstruction did not prevent the appearance of late degenerative changes on radiographs.

CONCLUSION
Present literature suggest following guidelines
* Conservative treatment for isolated ACL tear gives good long term results although with slightly higher risk of secondary meniscal injury.
* Primary ACL reconstruction is absolutely indicated in following scenarios
- associated meniscal injury
- High preinjury activity level
* delayed ACL reconstruction is recommended for patients with symptomatic instability
* ACL reconstruction has no effect on appearance of degenerative changes on radiographs

FUTURE PROSPECTS
We agree with Cochrane database study that there is a need for good quality, and well reported, randomized trials evaluating the effectiveness and cost-effectiveness of current methods of surgical treatment versus non-surgical treatment. The follow up of such trials should be at least 10 years so that the long term effects including degenerative changes can be established.


REFERENCES

1. Giove, T. P.; Miller, S. J., HI; Kent, B. E.; Sanford, T. L.; and Garrick, J. G.: Non-operative treatment of the torn anterior Cruciate ligament.J. Bone and Joint Surg., 65-A: 184-192, Feb. 1983.

2. JokI, P.; Kaplan, N.; Stovell, P.; and Keggi, K.: Non-operative treatment of severe injuries to the medial and anterior cruciate ligaments of the knee. ]. Bone and Joint Surg... 66-A: 741-744, June 1984.

3. Hawkins, R. J.; Misamore, G. W.; and Merritt, T. R.: Follow-up of the acute non-operative isolated anterior cruciate ligament tear. Am. J. Sports Med., 14: 205-210, 1986.

4. Clancy, W. G.,Jr.: Intra-articular reconstruction of the anterior cruciate ligament. Orthop. Clin. North America, 16: 181-189, 1985.


5. Caborn DN, Johnson BM. The natural history of the anterior cruciate ligament-deficient knee: A review. Clin Sports Med 1993;12:625-636.

6. Roos H, Adalberth T, Dahlberg L, Lohmander LS. Osteoarthritis of the knee after injury to the anterior cruciate ligament or meniscus: The influence of time and age. Osteoarthritis Cartilage 1995;3:261-267.

7. Marx RG, Jones EC, Angel M, Wickiewicz TL, Warren RF. Beliefs and Attitudes of Members of the American Academy of Orthopaedic Surgeons Regarding the Treatment of Anterior Cruciate Ligament Injury. Arthroscopy. 2003 Sep;19(7):762-70.

8.Kessler MA, Behrend H, Henz S, Stutz G, Rukavina A, Kuster MS.Function, osteoarthritis and activity after ACL-rupture: 11 years follow-up results of conservative versus reconstructive treatment. Knee Surg Sports Traumatol Arthrosc. 2008 May;16(5):442-8.

9. Casteleyn PP, Handelberg F . Non-operative management of anterior cruciate ligament injuries in the general population. J Bone Joint Surg Br. 1996, 78:446–451

10. Kostogiannis I, Ageberg E, Neuman P, Dahlberg L, Friden T, Roos H Activity level and subjective knee function 15 years after anterior cruciate ligament injury: a prospective, longitudinal study of nonreconstructed patients. Am J Sports Med. 2007, 35:1135–1143

11. Strehl A, Eggli S. The value of conservative treatment in ruptures of the anterior cruciate ligament (ACL). J Trauma. 2007, 62:1159–1162

12. Daniel DM, Stone ML, Dobson BE, Fithian DC, Rossman DJ, Kaufman KR. Fate of the ACL-injured patient: a prospective outcome study. Am J Sports Med. 1994;22:632-644.

13. Linko E, Harilainen A, Malmivaara A, Seitsalo S. Surgical versus conservative interventions for anterior cruciate ligament ruptures in adults. Cochrane Database Syst Rev. 2005 Apr 18;(2):

14. Sandberg R, Balkfors B, Nilsson B, Westlin N. Operative versus non-operative treatment of recent injuries to the ligaments of the knee. A prospective randomized study. Journal of Bone and Joint Surgery - American Volume 1987;69(8):1120–6.

15. Andersson C, Odensten M, Good L, Gillquist J. Surgical or nonsurgicalbtreatment of acute rupture of the anterior cruciate ligament. A randomized study with long-term follow-up. Journal of Bone and Joint Surgery - American Volume 1989;71(7):965–74.

16. D E Meuffels, M M Favejee, M M Vissers, M P Heijboer, M Reijman, and J A N VerhaarTen year follow-up study comparing conservative versus operative treatment of anterior cruciate ligament ruptures. A matched-pair analysis of high level athletesBr. J. Sports Med., May 2009; 43: 347 - 351.

17. Meunier A, Odensten M, Good L. Long-term results after primary repair or non-surgical treatment of anterior cruciate ligament rupture: a randomized study with a 15-year follow-up. Scand J Med Sci Sports. 2007 Jun;17(3):230-7

18. Fithian DC, Paxton EW, Stone ML, Luetzow WF, Csintalan RP, Phelan D, Daniel DM.Prospective trial of a treatment algorithm for the management of the anterior cruciate ligament-injured knee. Am J Sports Med. 2005 Mar;33(3):335-46.