Introduction

Cartilage regeneration is one of surgeons most compelling challenges. In the last twenty years different surgical techniques have been developed to treat cartilage defects. When the size of the lesions becomes bigger, the treatment becomes more challenging.

- Donor site morbidity is one of the principal contraindications of autologous osteochondral grafting in large defects. Addtionally, fibrocartilage will form between the plugs when mosaicplasty with higher numbers of plugs is performed.

- The use of ACI is not cost-effective, requiring two surgical procedures. This procedure is almost completely abandoned, for example, in Italy.

- Fresh osteochondral allografts have been widely used to treat large osteochondral defects of the knee, but many questions are still open regarding cartilage viability and preservation and bone integration.

Tissue bio-engeneering has helped the orthopedic surgeons producing multiple scaffolds for the treatment of larger defects, aiming to create three-dimensional scaffolds which act as templates for tissue development. Lately the awareness of the involvement of the subchondral bone in these lesions, resulted in the need to develop cell-free treatment strategies focused on the entire osteochondral unit. The “cell-free” osteochondral grafts have been developed with the aim to give specific regenerative signals to mesenchymal cells coming from the bone marrow. An ideal graft would be an off-the-shelf product from both a surgical and commercial standpoint, so many biomaterials have been proposed in the last years to induce cartilage “regeneration” in situ, directly in the site of lesion.

Content

To address the subchondral bone, designated three dimensional scaffolds have been developed to treat more extended chondral and osteochondral defects. Maioregen® (Fin-Ceramica SpA, Faenza, Italy)is a nanostructured biomimetic scaffold with a porous 3-dimensional trilayer composite structure, mimicking the whole osteochondral anatomy. This scaffold was introduced into clinical practice because a cell-free approach after animal studies showed good results in terms of both cartilage and bone tissue formation. Clinical studies have showed that the implantation of this biomimetic scaffold to treat chondral and osteochondral knee defects proved to be effective in terms of clinical outcome at a short follow-up time in a large patient population, even though altered findings have been detected at MRI.

More recently various components processed with tissue engineering have been proposed as a valid alternative because they can participate actively to the process of tissue regeneration and are able to integrate with healthy tissues. Agili-C™ (CartiHeal, Israel) is a recently developed cell-free, resorbable, bi-phasic scaffold made of inorganic calcium carbonate (aragonite). Aragonite is a biological material similar to human bone in its three- dimensional structure, pore interconnections and crystalline form of calcium carbonate (CaCO 3), with osteoconductive ability which make it suitable for bone repair. The calcium carbonate structures are gradually resorbed and replaced by functional bone tissue. This implant has been used mostly in the knee joint, but also other joints as the ankle and the big toe have been treated. Results are nowadays promising, with improvement of all the clinical scores at short and medium follow-up and with an MRI and X-ray aspect that no other scaffolds have shown before with good cartilage formation and scaffold reabsorption. Moreover the uniqness of this implant is that you can treat wide range of patients, including arthritic and non-arthrititc joints, single and multiple lesions as well as both chondral and osteochondral defects

References

Large fresh osteochondral allografts of the knee: a systematic clinical and basic science review of the literature. De Caro F, Bisicchia S, Amendola A, Ding L. Arthroscopy. 2015 Apr;31(4):757-65. doi: 10.1016/j.arthro.2014.11.025. Epub 2015 Feb 3. Review. PMID: 25660010

Treatment of Large Knee Osteochondral Lesions With a Biomimetic Scaffold: Results of a Multicenter Study of 49 Patients at 2-Year Follow-up. Berruto M, Delcogliano M, de Caro F, Carimati G, Uboldi F, Ferrua P, Ziveri G, De Biase CF. Am J Sports Med. 2014 Jul;42(7):1607-17. doi: 10.1177/0363546514530292. Epub 2014 Apr 28. PMID: 24778267

Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee. Delcogliano M, de Caro F, Scaravella E, Ziveri G, De Biase CF, Marotta D, Marenghi P, Delcogliano A. Knee Surg Sports Traumatol Arthrosc. 2014 Jun;22(6):1260-9. doi: 10.1007/s00167-013-2717-3. Epub 2013 Oct 22. PMID: 24146051

Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model.Kon E, Filardo G, Robinson D, Eisman JA, Levy A, Zaslav K, Shani J, Altschuler N. Knee Surg Sports Traumatol Arthrosc. 2014 Jun;22(6):1452-64. doi: 10.1007/s00167-013-2467-2. Epub 2013 Mar 12

Osteochondral regeneration with a novel aragonite-hyaluronate biphasic scaffold: up to 12-month follow-up study in a goat model. Kon E, Filardo G, Shani J, Altschuler N, Levy A, Zaslav K, Eisman JE, Robinson D. J Orthop Surg Res. 2015 May 28;10:81. doi: 10.1186/s13018-015-0211-y.

A novel aragonite-based scaffold for osteochondral regeneration: early experience on human implants and technical developments.Kon E, Robinson D, Verdonk P, Drobnic M, Patrascu JM, Dulic O, Gavrilovic G, Filardo G. Injury. 2016 Dec;47 Suppl 6:S27-S32. doi: 10.1016/S0020-1383(16)30836-1.

Agili-C implant promotes the regenerative capacity of articular cartilage defects in an ex vivo model. Chubinskaya S, Di Matteo B, Lovato L, Iacono F, Robinson D, Kon E. Knee Surg Sports Traumatol Arthrosc. 2018 Nov 1. doi: 10.1007/s00167-018-5263-1.

Autologous Matrix-Induced Chondrogenesis: A Systematic Review of the Clinical Evidence.Gao L, Orth P, Cucchiarini M, Madry H.Am J Sports Med. 2019 Jan;47(1):222-231. doi: 10.1177/0363546517740575. Epub 2017 Nov 21

Long-term follow-up evaluation of autologous chondrocyte implantation for symptomatic cartilage lesions of the knee: A single-centre prospective study.Berruto M, Ferrua P, Pasqualotto S, Uboldi F, Maione A, Tradati D, Usellini E. Injury. 2017 Oct;48(10):2230-2234. doi: 10.1016/j.injury.2017.08.005. Epub 2017 Aug 4.

Purpose

Unicompartmental OA is often characterized by the presence of bone marrow edema (BME) in the femoral condyle and tibial emi-plateau, which is responsible for significant pain. The aim of the present study is to describe the clinical outcome following injection of bone marrow concentrate (BMC) in the articular space and withing the BME areas.

Methods and Materials

Twenty-three patients (15 M and 8W, mean age: 56) were treated by harvesting 90 cc of bone marrow (60cc from the anterior iliac crest and 30cc from the tibia) to achieve 9cc of BMC after centrifugation in the OR. Under fluoroscopic guidance, 3 cc of BMC were injected intra-articularly and in both the BME areas in the femoral condyle and tibial plateau. Patients were prospectively evaluated up to 12 months’ follow-up by the following items: VAS for pain, IKDC subjective and objective, KOOS and Tegner Score. Small samples of BMC obtained from the tibia and the iliac crest were also sent to lab for characterization

Results

No intra-op adverse events has occurred. A significant reduction in VAS for pain was reported at 3 months (from 6.2 ±1.9 to 3.3 ±0.9 ), with stable results up to the final evaluation at one year. Similarly, IKCD-subj. increased from 42.8 ±13.1 to 59.5±15.2 at 3 months, without further statistical improvement up to 12 months. A similar trend was also documented also in all the subscales of KOOS. Two patients were considered failed and underwent other surgical treament. In terms of cellularity, lab analysis revealed significantly higher number of mesenchymal stem cells in the crest-harvested BMC compared to tibia.

Conclusion

Intra-articular and intra-osseous injections of BMC is an easy and safe treatment approach in patients affected by unicompartmental OA associated to BME. Short-term evaluation revealed decrease of pain and improvement in knee function, that should be confirmed at longer follow-up