Cell-Free Scaffolds for the Treatment of Chondral and Osteochondral Lesions


Author

Study design

Scaffold

Follow-up period

Number of patients

Age

Gender

Site

Mean defect size (cm2)

Kusano T, KSSTA 2012 [14]

Retrospective study

Collagen matrix

29 m

38a

26 y

23 M, 17 W

20 patella, 16 MFC, 4 LFC

3.9

Schiavone Panni A, Int J Immunopathol Pharmacol 2011 [15]

Case series

Collagen matrix

36 m

17

39 y

10 M, 7 W

na

na

Gille J, KSSTA 2010 [17]

Case series

Collagen matrix

36 m

27

37 y

16 M, 11 W

7 MFC, 3 LFC, 9 patella, 2 trochlea, 6 multiple

4.2

Gille J, Arch Orthop Trauma Surg 2013 [16]

Case series

Collagen matrix

24 m

57

37 y

38 M, 19 W

32 MFC, 6 LFC, 4 trochlea, 15 patella

3.4

Gille J, Cartilage 2016 [7]

Case series

Collagen matrix

16 y

14

35 y

6 M, 8 W

7 MFC, 4 patella, 4 multipleb

3.6

Stanish WD, JBJS Am 2013 [24]

Randomized controlled trial

BST-Cargel

12 m

80 (41 BST, 39 MFX)

34 y

48 M, 32 W

78 MFC, 2 LFC

2.3

Shive MS, Cartilage 2015 [25]

Randomized controlled trial

BST-Cargel

60 m

60 (34 BST, 26 MFX)

34 y

36 M, 24 W

na (all femoral condyles)

2.4


aTwo cases were bilateral

bOne case was bilateral



Benthien and Behrens first described the AMIC technique [11, 12] with indications limited to lesions under 1.5 cm2 [12]. Later, Piontek et al. [13] introduced a modification to the technique that allowed the insertion of the matrix under dry arthroscopy and fibrin glue fixation, after marrow stimulation of the defect. Kusano et al. [14] observed significant improvements in all clinical scores at 28 months follow-up. However, a retrospective review of 38 patients treated with a collagen-based matrix for full-thickness defects of the knee showed an incomplete defect filling observed at MRI in most of the cases. Furthermore, satisfactory clinical results were described by Schiavone Panni et al. [15] in 17 patients, with a 76.5% satisfaction rate at 36 months postoperatively. On the other hand, more than half of the MRI scans performed showed the presence of subchondral bone edema. Gille et al. [16] applied this technique on 57 patients with cartilage defects at various knee sites, confirming the safety of the procedure and showing significant clinical improvement at 24 months follow-up. They also reported 87% satisfaction rate in 27 patients at 36 months follow-up, paired with a moderate to complete filling of the defect at MRI, regardless of patient’s age or number of previous surgeries [17]. Finally, they recently updated their first series of 57 patients at 16 years follow-up [7]. Among the 18 patients evaluated at long term, 4 failed and underwent arthroplasty. The remaining cases showed a slight increase of clinical scores compared to mid-term evaluation. However, the reliability of these positive results is limited due to the low number of patients available for the final follow-up evaluation.

Other authors tried to improve the biological potential of these one-step procedures by adding a bone marrow concentrate (BMC) prepared during the same surgical session. The promising results showed by early reports [18, 19] have later been confirmed at longer follow-up [20, 21]. However, these augmentation procedures are outside the scope of this chapter and will be described elsewhere.

Finally, a further option to augment marrow-stimulation procedures for the treatment of chondral layer defects came from chitosan, a biodegradable hydrogel that showed optimal biocompatibility and the ability to support chondrogenesis in vitro and in the animal model [22]. BST-CarGel technique involves the use of chitosan hydrogel mixed with autologous whole blood, which is applied into a microfractured cartilage defect by arthroscopy, in order to stabilize the clot and, in the end, improve the repair process [23]. The results of a multicenter randomized controlled trial were first reported by Stanish et al., who compared 41 patients undergoing BST-CarGel with 39 undergoing microfractures alone. At 12 months, safety and clinical improvement offered by both procedures were comparable, but the treatment group achieved greater lesion filling and hyaline-like tissue at T2 mapping [24]. Later, a second study on the same series showed that these results were maintained up to 5 years after surgery [25]. The superior quality of the regenerative tissue offered by augmented microfractures was confirmed by macroscopic and histologic evaluations in nearly half of these patients, showing better features in most of the parameters for the treatment group, where a hyaline-like cartilage was observed [26].



11.3 Osteochondral Scaffolds


Since preclinical and clinical evidence increasingly supported the rationale for treating the entire osteochondral unit, different multi-layered products have been proposed in order to mimic both subchondral bone and the cartilaginous layer. Among these, three have been mainly investigated for clinical use and documented by clinical trials available in the current literature [Table 11.2].


Table 11.2
Summary of the studies dealing with the clinical use of acellular osteochondral scaffolds for cartilage repair














































































































































































































































































Author

Study design

Scaffold

Follow-up period

Number of patients

Age

Gender

Site

Mean defect size (cm2)

Indication

Joshi N, AJSM 2012 [38]

Case series

Trufit

24 m

10

34 y

4 M, 6 W

10 Patella

2.6

Osteochondral patellar defects

Dhollander AA, Arthroscopy 2012 [37]

Case series

Trufit

12 m

20

32 y

8 M, 12 W

8 MFC, 4 LFC, 5 patella, 3 trochlea

0.8

Focal articular cartilage defects

Bekkers JE, AJSM 2013 [35]

Case series

Trufit

12 m

13

32 y

na

7 MFC, 6 LFC

1.9

Focal articular cartilage/osteochondral defects

Hindle P, KSSTA 2014 [39]

Retrospective study

Trufit

22 m

35 Trufit

39 y

23 M, 12 W

32 MFC, 2 LFC, 1 trochlea

na

Articular cartilage defects

31 mosaicplasty

Bedi A, Cartilage 2010 [29]

Case series

Trufit

21 m

26

29 y

na

26 trochlea

na

Donor sites in OATS

Barber FA, Arthroscopy 2011 [30]

Case series

Trufit

na

9

40 y

8 M, 1 W

na

na

Donor sites in OATS

Carmont MR, Arthroscopy 2009 [34]

Case report

Trufit

24

1

18 y

1 M

LFC

8.0

Degenerative osteochondral defect

Gelber PE, Knee 2014 [36]

Case series

Trufit

45 m

57

36 y

51 M, 6 W

22 MFC, 15LFC, 20 trochlea

na

Focal articular cartilage defects

Quarch VM, Arch Orthop Trauma Surg 2014 [31]

Retrospective study

Trufit

25 m

37

38 y

12 M, 9 W

37 dorsal MFC

5.5

Donor sites in OATS (comparative vs. empty defect)

Kon E, Injury 2010 [43]

Case series

Maioregen

26 w

13

37 y

10 M, 3 W

4 MFC, 2 LFC, 5 patella, 4 trochlea

2.8

Articular cartilage defects

Kon E, AJSM 2011 [44]

Case series

Maioregen

24 m

28

35 y

9F, 19 M

8 MFC, 5 LFC, 12 patella, 7 trochlea, 2 lateral tibial plateau

2.9

Articular cartilage defects

Kon E, AJSM 2014 [45]

Case series

Maioregen

60 m

27

35 y

9F, 18 M

7 MFC, 5 LFC, 11 patella, 7 trochlea, 2 tibial plateau

2.9

Articular cartilage defects

Kon E, J Mater Sci Mater Med 2014 [46]

Case series

Maioregen

24 m

79

31 y

63 M, 16 W

41 MFC, 26 LFC, 15 trochlea

3.2

Articular cartilage defects

Verdonk P, Bone Joint J 2015 [47]

Case series

Maioregen

24 m

38

30 y

23 M, 15 W

23 MFC, 7 LFC, 5 patella, 3 trochlea

3.7

Articular cartilage defects

Filardo G, AJSM 2013 [48]

Case series

Maioregen

24 m

27

25 y

19 M, 8 W

17 MFC, 10 LFC

3.4

Osteochondritis dissecans

Delcogliano M, KSSTA 2014 [49]

Case series

Maioregen

24 m

19a

33 y

16 M, 5 W

10 MFC, 7 LFC, 3 lateral tibial plateau

5.2

Large osteochondral defects

Berruto M, AJSM 2014 [50]

Case series

Maioregen

24 m

49

37 y

37 M, 12 W

33 MFC, 11 LFC, 4 tibial plateau, 1 trochlea

4.3

Large osteochondral defects

Marcacci M, KSSTA 2013 [52]

Case series

Maioregen

36 m

43

40 y

33 M, 10 W

na

4.6

Articular cartilage defects in unicompartmental OA

Filardo G, Knee 2013 [51]

Comparative study

Maioregen

24 m

33

39 y

24 M, 9 W

11, MFC, 9 LFC, 13 trochlea, 9 patella, 5 tibial plateau

4.5

“Complex” articular cartilage defect

Di Martino A, Injury 2015 [55]

Case series

Maioregen

24 m

23

38 y

19 M, 4 W

12 MFC, 9 LFC, 6 trochlea, 1 tibial plateau, 1 patella

3.2

Articular cartilage defects in early OA knees

Berruto M, Knee 2016 [56]

Case series

Maioregen

24 m

11

52 y

5 M, 6 W

na

3.5

Spontaneous focal osteonecrosis of the knee

Christensen BB, KSSTA 2016 [57]

Case series

Maioregen

30 m

8

27 y

5 M, 3 W

3 MFC, 1 patella, 3 talus

3.0

Focal osteochondral defects


aTwo patients were lost at follow-up

The first one is a polymeric PLGA-PGA and calcium sulfate bi-layer scaffold (Trufit CB™, Smith & Nephew, USA), whose resorbable structure has been developed to allow a complete filling of the osteochondral defect with regenerating tissue [27]. After promising preclinical findings with no cell augmentation [28], the scaffold was then implemented in clinical practice with the indication to backfill autologous grafts donor sites. Bedi et al. [29] observed that the implant had a slow MRI improvement after implantation into mosaicplasty donor sites, whereas Barber et al. reported no signs of maturation, osteoconduction, or ossification in CT scans performed in nine patients after Trufit™ implantation [30]. Finally, Quarch et al. [31] showed that filling donor site defects with Trufit™ in 21 patients, who underwent OAT, did not produce any clinical benefit in terms of donor site morbidity compared to 16 patients where the harvest site was left empty.

Most of the available studies reported the results of implants for the treatment of focal articular defects, with controversial results [32, 33]. Carmont et al. first reported promising findings in a symptomatic chondral lesion of the lateral femoral condyle of an 18-year-old patient. Although unfavorable MRI findings were observed at an intermediate postoperative interval, the patient reported complete relief of symptoms and returned to sports within 24 months follow-up, suggesting a long maturation time for the scaffold [34]. Bekkers et al. evaluated 13 patients clinically and using delayed gadolinium-enhanced quantitative MRI, at a mean of 12 months after Trufit implantation into femoral condyles defects. Both clinical scores improvement and cartilage-like signal at MRI were observed [35]. Gelber et al. evaluated 57 patients at mid-term follow-up showing significant improvements in clinical parameters and recovery to pre-injury physical activity level. However, despite good cartilage integration, MRI evaluation showed high heterogeneity and no filling of the subchondral bone layer. Finally, clinical performance was lower for larger lesions [36].

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Jul 31, 2017 | Posted by in ORTHOPEDIC | Comments Off on Cell-Free Scaffolds for the Treatment of Chondral and Osteochondral Lesions

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