Fig. 1

Fig. 1

Pre-op X-ray and RM images from the patients included in the study. X-Ray (A) and arthro-RM (B) images from patient 1 showing a lesion in the anterior labrum and a specular chondral lesion in the acetabulum and femoral head, and a subchondral cyst. X-Ray (C) and arthro-RM (D) from patient 2, showing a torn anterior-superior labrum, with a chondral flap associated in the superior acetabular quadrant.

Fig. 2

Fig. 2

First (A) and second steps (B-E) of HD-ACI procedure. In the first step a biopsy of healthy cartilage is taken arthroscopically (A). In the second step the hip was dislocated following the Ganz's procedure (B) and chondral lesions were exposed (C). After seeding the chondrocytes at a 5 million per cm2 density onto the membrane previously cut according the size and shape, it was placed and attached to the defect (D). After checking that membrane was properly fixed, surgery ended reducing the trochanter osteotomy (E).

Fig. 3

Fig. 3

Post-op X-ray images showing reduction of trochanter osteotomy with 2 cannulated screws in patient 1 (A) and 2 (B).

Fig. 4

Fig. 4

Three-year arthro-MRI for patient 1 (A) and 2 (B). dGEMRIC and T2 relaxation time mapping corresponding to patient 2 (C).

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Abstract

Introduction

In this work we describe the use of high-density autologous chondrocyte implantation (HD-ACI) to treat 2 patients with chondral defects in the hip.

Case Presentation

Two male, 35- and 37-year-old, with chondral lesions and femoroacetabular impingement (FAI) were included. Chondrocytes were isolated expanded in vitro and then implanted at a density of 5 million cells per cm2 onto a type I/III porcine collagen membrane. None of the patients had surgery-derived complications. Pain disappeared in both cases at 6 months after surgery and was maintained until follow-up end (36 months). International Hip Outcome Tool (iHOT) score increased at 6 and 12 months and then leveled off until month 36.Three-year arthro-MRI showed the cartilage defects had been filled with a material similar to the surrounding healthy cartilage.

Conclusion

HD-ACI is a safe and effective technique for focal cartilage lesion treatment in patients affected by evolved FAI.

Introduction

Cartilage defects in the hip joint are relatively frequent and they are associated with pain and functional limitations that finally evolve into joint degeneration and osteoarthritis.1x1Jordan, MA, Van Thiel, GS, Chahal, J et al. Operative treatment of chondral defects in the hip joint: a systematic review. Curr Rev Musculoskelet Med. 2012; 5: 244–253

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Trauma, femoroacetabular impingement (FAI), labral tears, dysplasia, among others, are the most frequent causes of articular hip cartilage lesions.2x2Anderson, SE, Siebenrock, KA, and Tannast, M. Femoroacetabular impingement. Eur J Radiol. 2012; 81: 3740–3744

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Since hyaline cartilage has a limited ability for self-repair, cartilage repair represents a challenge in current orthopedic traumatology. All treatment options pursuit to replace damaged cartilage with a tissue showing the same biological and biomechanical properties as the native one.3x3Buckwalter, JA. Articular cartilage: injuries and potential for healing. J Orthop Sports Phys Ther. 1998; 28: 192–202

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Autologous chondrocyte implantation (ACI) has evolved from the original method in which the cells, suspended in liquid medium, were implanted under a periosteal flap,4x4Brittberg, M, Lindahl, A, Nilsson, A et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New Engl J Med. 1994; 331: 889–895

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to current use of a carrier to maintain cells over defect.5x5Kreuz, PCKR, Niemeyer, P, Uhl, M et al. Treatment of a focal articular cartilage defect of the talus with polymer-based autologous chondrocyte implantation: a 12-year follow-up period. J Foot Ankle Surg. 2017; 56: 862–864

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In all of them, chondrocytes are obtained from a non-weight-bearing area biopsy.4x4Brittberg, M, Lindahl, A, Nilsson, A et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New Engl J Med. 1994; 331: 889–895

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| Google ScholarSee all References
, 5x5Kreuz, PCKR, Niemeyer, P, Uhl, M et al. Treatment of a focal articular cartilage defect of the talus with polymer-based autologous chondrocyte implantation: a 12-year follow-up period. J Foot Ankle Surg. 2017; 56: 862–864

Abstract | Full Text | Full Text PDF | PubMed | Scopus (6)
| Google ScholarSee all References
, 6x6Fontana, A and de Girolamo, L. Sustained five-year benefit of autologous matrix-induced chondrogenesis for femoral acetabular impingement-induced chondral lesions compared with microfracture treatment. Bone Joint J. 2015; 97-b: 628–635

Crossref | PubMed | Scopus (61)
| Google ScholarSee all References
, 7x7Brittberg, M. Autologous chondrocyte transplantation. Clin Orthop Relat Res. 1999; 367: S147–S155

Crossref | PubMed | Scopus (253)
| Google ScholarSee all References
One of the reasons for the lack of use of ACI for treating hip articular cartilage lesions is the poor accessibility of the joint arthroscopically due to technical skills or difficult open access which increases the risk of avascular necrosis when dislocating the hip.6x6Fontana, A and de Girolamo, L. Sustained five-year benefit of autologous matrix-induced chondrogenesis for femoral acetabular impingement-induced chondral lesions compared with microfracture treatment. Bone Joint J. 2015; 97-b: 628–635

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| Google ScholarSee all References

It has been demonstrated that cell density may drastically influence the biological and histological properties of the neoformed tissue after chondrocyte implantation.8x8Guillén-García, P., Rodríguez-Iñigo, E., Guillén-Vicente, I. et al. Increasing the dose of autologous chondrocytes improves articular cartilage repair: histological and molecular study in the sheep animal model. Cartilage. 2014; 5: 114–122

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Taking into account the importance of cell density, a novel membrane-based ACI approach, called high-density ACI (HD-ACI), has recently been developed. This technique consists in increasing the number of chondrocytes seeded in the same I/III collagen membrane from porcine origin used for MACI 5-fold.9x9Lopez-Alcorocho, J.M., Aboli, L., Guillen-Vicente, I. et al. Cartilage defect treatment using high-density autologous chondrocyte implantation: two-year follow-up. Cartilage. 2018; 9: 363–369

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,10x10López-Alcorocho, J.M., Guillén-Vicente, I., Rodríguez-Iñigo, E. et al. High-density autologous chondrocyte implantation as treatment for ankle osteochondral defects. Cartilage. 2021; 12: 307–319

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The results obtained after 2 year follow-up in patients with articular cartilage defects in the knee9x9Lopez-Alcorocho, J.M., Aboli, L., Guillen-Vicente, I. et al. Cartilage defect treatment using high-density autologous chondrocyte implantation: two-year follow-up. Cartilage. 2018; 9: 363–369

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and ankle10x10López-Alcorocho, J.M., Guillén-Vicente, I., Rodríguez-Iñigo, E. et al. High-density autologous chondrocyte implantation as treatment for ankle osteochondral defects. Cartilage. 2021; 12: 307–319

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demonstrated that HD-ACI is a safe and effective technique and could be used to treat chondral defects in the hip joint. In this work we describe the results obtained in the first two patients with chondral lesion in the hip treated with HD-ACI and followed-up for 36 months.

Materials and methods

The study was performed in accordance to the ethical standards of the Helsinki Declaration of 1964, revised in 2013. Patients signed and informed consent and the study was approved by the Research and Education Committee of CEMTRO Clinic (Study number: 003/2017). Two male, 35-and 37-year-old patients with chondral lesions in the hip were included in this study. One of them (patient 1) had two specular grade IV Outerbridge lesions, located in the acetabulum (140 mm2) and in the femoral head (300 mm2) of the left limb (Fig. 1A). The other patient (patient 2) had a grade IV Outerbridge chondral lesion 360 mm2 in size, located in the femoral head of the right limb (Fig. 1C). Both patients presented complete motion range but showed positive impingement and decompression tests.

Fig. 1 Opens large image

Fig. 1

Pre-op X-ray and RM images from the patients included in the study. X-Ray (A) and arthro-RM (B) images from patient 1 showing a lesion in the anterior labrum and a specular chondral lesion in the acetabulum and femoral head, and a subchondral cyst. X-Ray (C) and arthro-RM (D) from patient 2, showing a torn anterior-superior labrum, with a chondral flap associated in the superior acetabular quadrant.

Arthro-RM images evidenced in patient 1 a torn anterior labrum and a specular chondral lesion in the acetabulum and femoral head, with the presence of a subchondral cyst (Fig. 1B). In patient 2, arthro-RM images revealed a torn anterior-superior labrum, with a chondral flap associated in the superior quadrant of the acetabulum and FAI (Fig. 1D). In both cases focal cartilage lesions associated with hip impingement of the CAM-type were identified and a HD-ACI was prescribed.

HD-ACI is a two-step technique. During the first arthroscopic surgery, a femoroacetabular osteoplasty and labrum suture was performed. In both patients a sample of healthy cartilage, similar to 3 or 4 rice grains in size, was taken from a healthy nonweight-bearing area surrounding the femoral head pit (Fig. 2A). The culture process was performed as previously described.9x9Lopez-Alcorocho, J.M., Aboli, L., Guillen-Vicente, I. et al. Cartilage defect treatment using high-density autologous chondrocyte implantation: two-year follow-up. Cartilage. 2018; 9: 363–369

Crossref | PubMed | Scopus (14)
| Google ScholarSee all References
,10x10López-Alcorocho, J.M., Guillén-Vicente, I., Rodríguez-Iñigo, E. et al. High-density autologous chondrocyte implantation as treatment for ankle osteochondral defects. Cartilage. 2021; 12: 307–319

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| Google ScholarSee all References
In a second surgery, cartilage defects were exposed by Ganz's safe hip surgical dislocation (Figs. 2B and 2C). Chondral lesions were debrided and HD-ACI was carried-out following the previously published procedure.9x9Lopez-Alcorocho, J.M., Aboli, L., Guillen-Vicente, I. et al. Cartilage defect treatment using high-density autologous chondrocyte implantation: two-year follow-up. Cartilage. 2018; 9: 363–369

Crossref | PubMed | Scopus (14)
| Google ScholarSee all References
,10x10López-Alcorocho, J.M., Guillén-Vicente, I., Rodríguez-Iñigo, E. et al. High-density autologous chondrocyte implantation as treatment for ankle osteochondral defects. Cartilage. 2021; 12: 307–319

Crossref | PubMed | Scopus (7)
| Google ScholarSee all References
The cells resuspended in culture medium were seeded onto a porcine type I/III collagen membrane (Chondro-Gide, Geistlich Biomaterials, Wolhusen, Switzerland) at a rate of 5 million cells per cm2 of lesion. After waiting 10 minutes, the cells were adsorbed onto the membrane, and then the membrane was sutured to the adjacent bone and sealed to the injury with Tissucol (Baxter, Madrid, Spain) (Figs. 2D and 2E). Patients were kept under non weight-bearing conditions for 6 weeks. After the 6th week, patients started active physical therapy, with progressive hold up of the affected limb with the aim of regaining any lost range of motion.

Fig. 2 Opens large image

Fig. 2

First (A) and second steps (B-E) of HD-ACI procedure. In the first step a biopsy of healthy cartilage is taken arthroscopically (A). In the second step the hip was dislocated following the Ganz's procedure (B) and chondral lesions were exposed (C). After seeding the chondrocytes at a 5 million per cm2 density onto the membrane previously cut according the size and shape, it was placed and attached to the defect (D). After checking that membrane was properly fixed, surgery ended reducing the trochanter osteotomy (E).

The quality-of-life outcome was measured by the International Hip Outcome Tool (iHOT-33) questionnaire, which was filled-out by the patient before the first surgery, and at 6, 12, 24, and 36 months after the second one. Cell implants were also evaluated by magnetic resonance images (MRI) at 12 and 36 months. In one of the patients (patient 2), reduction of glycosaminoglycan content was studied by delayed gadolinium enhanced Magnetic Resonance Imaging of cartilage (dGEMRIC) method.T2 relaxation time mapping (T2 mapping) of cartilage repair tissue was used to reveal reduced collagen stratification and anisotropy.

Results

After chondrocyte implantation none of the patients had surgery-derived complications. Fig. 3 shows X-ray images from both patients after surgery. Trochanter fixation with 2 cannulated screws after Ganz's safe hip surgical dislocation is depicted in Fig. 3. Three weeks after surgery, staples were removed and patients started to walk with 2 crutches (50% of weight bearing). With respect to pain, patients had a pre-op VAS score of 4 and 2 respectively and pain disappeared in both cases (VAS = 0) at 6 months after surgery and was maintained until the end of follow-up (36 months). iHOT questionnaire scores were 50 and 42 and increased at 6 and 12 months to 72 and 90 in one case and 80 and 95 in the other patients. Then, iHOT value stabilized at 24 and 36 months in both cases (iHOT scores at 24 months in patient 1 was 91 and 93 in patient 2; iHOT values at 36 months were 92 and 94, respectively).

Fig. 3 Opens large image

Fig. 3

Post-op X-ray images showing reduction of trochanter osteotomy with 2 cannulated screws in patient 1 (A) and 2 (B).

The 3-year arthro-RMI in both cases showed the cartilage defects filled by a material similar to the surrounding healthy cartilage (Fig. 4). In patient 2, dGEMRIC and T2 mapping revealed that the material filling the defect had glycosaminoglycans suggesting the hyaline or hyaline-like nature of this neoformed tissue (Figs. 4B and 4C).

Fig. 4 Opens large image

Fig. 4

Three-year arthro-MRI for patient 1 (A) and 2 (B). dGEMRIC and T2 relaxation time mapping corresponding to patient 2 (C).

Discussion

In this work we present results for the first two patients with hip lesions treated with HD-ACI with a 36-month follow up. Pain measured disappears 6 months after surgery maintaining this score 36 months after the procedure. iHOT questionnaire, showed significant improvement 6 months after surgery, increasing at 12 months and maintaining the score longer than 36 months. Focusing on these results we can conclude that treatment with HD-ACI has shown a relevant clinical benefit in the treatment of focal hip cartilage lesions.

Imaging techniques, X-ray and MRI showed correlation between radiologic signs and clinical response. Analysing images obtained using dGemric and T2 Mapping in one of the patients, demonstrate a good quality of neoformed cartilage producing proteoglicanes.

Both patients were scoped at the time of screw removal surgery, observing a cartilage with normal appearance, and texture. Although no histological studies were possible in these patients, we have previously demonstrated in biopsies of patients with knee and ankle lesions treated with HD-ACI, that histological analysis show that the new cartilage is hyaline-like.9x9Lopez-Alcorocho, J.M., Aboli, L., Guillen-Vicente, I. et al. Cartilage defect treatment using high-density autologous chondrocyte implantation: two-year follow-up. Cartilage. 2018; 9: 363–369

Crossref | PubMed | Scopus (14)
| Google ScholarSee all References
,10x10López-Alcorocho, J.M., Guillén-Vicente, I., Rodríguez-Iñigo, E. et al. High-density autologous chondrocyte implantation as treatment for ankle osteochondral defects. Cartilage. 2021; 12: 307–319

Crossref | PubMed | Scopus (7)
| Google ScholarSee all References

The only limitation of these techniques is that for the time being we perform this technique in an open manner by safe hip dislocation as described by Ganz.

Conclusion

Results obtained in the first two HD-ACI techniques for the treatment of cartilage lesions in hip patients show this is a safe and effective technique for focal cartilage lesion treatment in patients affected by evolved FAI.

Informed patient consent

Complete written informed consent was obtained from the patient for the publication of this study and accompanying images.

CRediT authorship contribution statement

RTE: patient recruitment, surgery, paper writing; JMLA: data collection and analysis, paper writing; ERI: data analysis, paper writing; IGV: surgery, review of paper; MGV: follow-up of patients, data analysis; MEDN: surgery, review of paper; LA: follow-up of patients, data collection; TFFJ: follow-up of patients, review of paper; PGG: surgery, paper writing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We would like to remember our friend and colleague Dr. Luis Betancourt. This work is dedicated to his memory.

We also thank Mario Wensell for carefully revising the linguistics for this article.

Funding

This work has been financed by Fundación Dr. Pedro Guillén.

References

  1. 1Jordan, MA, Van Thiel, GS, Chahal, J et al. Operative treatment of chondral defects in the hip joint: a systematic review. Curr Rev Musculoskelet Med. 2012; 5: 244–253
  2. 2Anderson, SE, Siebenrock, KA, and Tannast, M. Femoroacetabular impingement. Eur J Radiol. 2012; 81: 3740–3744
  3. 3Buckwalter, JA. Articular cartilage: injuries and potential for healing. J Orthop Sports Phys Ther. 1998; 28: 192–202
  4. 4Brittberg, M, Lindahl, A, Nilsson, A et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New Engl J Med. 1994; 331: 889–895
  5. 5Kreuz, PCKR, Niemeyer, P, Uhl, M et al. Treatment of a focal articular cartilage defect of the talus with polymer-based autologous chondrocyte implantation: a 12-year follow-up period. J Foot Ankle Surg. 2017; 56: 862–864
  6. 6Fontana, A and de Girolamo, L. Sustained five-year benefit of autologous matrix-induced chondrogenesis for femoral acetabular impingement-induced chondral lesions compared with microfracture treatment. Bone Joint J. 2015; 97-b: 628–635
  7. 7Brittberg, M. Autologous chondrocyte transplantation. Clin Orthop Relat Res. 1999; 367: S147–S155
  8. 8Guillén-García, P., Rodríguez-Iñigo, E., Guillén-Vicente, I. et al. Increasing the dose of autologous chondrocytes improves articular cartilage repair: histological and molecular study in the sheep animal model. Cartilage. 2014; 5: 114–122
  9. 9Lopez-Alcorocho, J.M., Aboli, L., Guillen-Vicente, I. et al. Cartilage defect treatment using high-density autologous chondrocyte implantation: two-year follow-up. Cartilage. 2018; 9: 363–369
  10. 10López-Alcorocho, J.M., Guillén-Vicente, I., Rodríguez-Iñigo, E. et al. High-density autologous chondrocyte implantation as treatment for ankle osteochondral defects. Cartilage. 2021; 12: 307–319

 

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