Treatment of hallux rigidus by a novel bi- phasic aragonite-based implant: results of a two year multi-centre clinical trial Matej Drobnič, Francesca Vannini, Elizaveta Kon, Oliver Dulić, Vaso Kecojević, Bogdan Andor, Nir Altschuler & Dror Robinson International Orthopaedics ISSN 0341-2695 International Orthopaedics (SICOT) DOI 10.1007/s00264-020-04872-8 1 23 Your article is protected by copyright and all rights are held exclusively by SICOT aisbl. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com”. 1 23 Author's personal copy International Orthopaedics https://doi.org/10.1007/s00264-020-04872-8 ORIGINAL PAPER Treatment of hallux rigidus by a novel bi-phasic aragonite-based implant: results of a two year multi-centre clinical trial Matej Drobnič1,2 & Francesca Vannini3 & Elizaveta Kon4,5,6 & Oliver Dulić7,8 & Vaso Kecojević7 & Bogdan Andor9 & Nir Altschuler10 & Dror Robinson11 Received: 27 October 2020 /Accepted: 3 November 2020 # SICOT aisbl 2020 Abstract Purpose The two year results of a multi-centre clinical trial were examined to evaluate surgical treatment of hallux rigidus using a novel, bi-phasic, biodegradable, and cell-free aragonite-based scaffold (Agili-C™, CartiHeal Ltd, Israel). Methods Twenty patients with moderate-to-severe hallux rigidus were recruited. After thorough metatarsophalangeal joint (MTPJ-1) debridement, the scaffolds were implanted into the defect centre. Eight patients received concomitant osteotomy. Treatment outcome was followed clinically (Pain VAS, FAAM-ADL, FAAM-Sport, AOFAS-HMIS, maximum active range of extension ROM-EXT, and flexion ROM-FLEX), and by medical imaging, at six month intervals for two years. Adverse events were recorded throughout the study follow-up period. Results Significant clinical improvement over time was observed in all evaluated parameters (screening to final evaluation averages: Pain VAS 59 to 26, FAAM-ADL 57 to 77, FAAM-Sport 39 to 66, AOFAS-HMIS 51 to 81, ROM-EXT 18° to 36°), except for ROM-FLEX. Radiographs showed stable MTPJ-1 width over the two years in 17/18 cases (94%). MRI demonstrated progressive implant biodegradation, coupled with articular cartilage and subchondral bone regeneration, with a repair tissue defect fill of 75–100% in 14/17 (82%) subjects at their final visit. Revision surgery with implant removal was performed in two patients. Conclusion Bi-phasic, osteochondral, biodegradable, aragonite-based scaffold demonstrated positive clinical outcome and a good safety profile in the treatment of medium-to-advanced hallux rigidus. According to the medical imaging, this implant has the potential to restore the entire osteochondral unit of metatarsal head. Keywords Agili-C . Osteochondral . Aragonite . Biodegradable . Bi-phasic . Cartilage . Great toe . Metatarsophalangeal . Osteoarthritis . Joint space . Osteophytes . Defect fill * Matej Drobnič 6 Department of Traumatology, Orthopedics and Disaster Surgery, [email protected] Sechenov First Moscow State Medical University, Moscow, Russia 7 Department for Orthopedic Surgery and Traumatology, Clinical 1 Department of Orthopedic Surgery, University Medical Centre Center of Vojvodina, Novi Sad, Serbia Ljubljana, Zaloška ulica 9, SI-1000 Ljubljana, EU, Slovenia 8 2 Chair of Orthopedics, Medical Faculty, University of Ljubljana, Medical Faculty, University of Novi Sad, Novi Sad, Serbia Ljubljana, Slovenia 9 Department of Orthopedics, Victor Babes University of Medicine 3 Clinic 1, Orthopedic Institute Rizzoli, Bologna University, and Pharmacy, Timisoara, Romania Bologna, Italy 10 CartiHeal, Kfar Saba, Israel 4 Humanitas Clinical and Research Center – IRCCS, Milan, Italy 5 Department of Biomedical Sciences, Humanitas University, 11 Faculty of Medicine, Hasharon Hospital Affiliated to Tel Aviv Milan, Italy University, Petah Tikwa, Israel Author's personal copy International Orthopaedics (SICOT) Introduction approved individually by each participating institution. Adult subjects with symptomatic hallux rigidus were enrolled. The Hallux rigidus is the most common arthritic condition in the inclusion criteria were the following: age 18 years or older, foot, with cartilage degeneration, synovitis, and osteophyte osteoarthritis of MTPJ-1, presence of good bone stock, formation of the first metatarsophalangeal joint (MTPJ-1), physically and mentally willing and able to comply with causing activity-related pain and stiffness associated with re- post-operative rehabilitation, and routinely scheduled clinical stricted dorsiflexion [1]. The estimated incidence of this con- and radiographic visits. The main exclusion criteria were any dition is 2.5% in subjects over 50, with a 2:1 female predom- past or present evidence of infection of the treated joint, any inance [2]. Despite known aetiology, such as long first ray, known malignant tumour of the foot, known inflammatory abnormally elevated or abducted first metatarsal (MT-1), pre- arthropathy or crystal-deposition arthropathy, and history of vious trauma, and positive family history of increased inci- any significant systemic disease. dence of hallux rigidus, most cases are idiopathic. According to clinical and radiographic criteria, Coughlin and Subjects and surgical intervention Shurnas graded MTPJ-1 degeneration into five (0–4) stages [3]. Initial treatment is typically conservative [4], but due to Twenty patients (11 female, 9 male) 56 (13) years, BMI 27.5 the ongoing degenerative process, surgical treatment is war- (3.4) kg/m2 were enrolled and treated with the study device. ranted in about half of the cases [5]. The golden-standard for Based on Coughlin and Shurnas criteria, the enrolled patients surgical interventions are MTPJ-1 cheilectomy without/with suffered from hallux rigidus grades 2 (7 pts), 3 (10 pts), and 4 dorsiflexion osteotomy of proximal phalanx for symptomatic (3 pts). Patients were operated on in an outpatient surgery hallux rigidus grades 1 and 2 [6], or MTPJ-1 arthrodesis in setting using general, spinal, or peripheral anaesthesia. later stages of the disease [7]. Alternatively, MTPJ-1 motion- Routine intra-operative antibiotic prophylaxis was adminis- preserving surgery may be performed, such as decompression tered, and a tourniquet was used upon surgeon’spreference. MT-1 osteotomy [8], inter-positional arthroplasty with local A dorsomedial approach to the MTPJ-1 was typically used. soft-tissues [9, 10], synthetic absorbable biomaterials (poly- First, the synovitis and osteophytes were debrided, and the urethane-urea [11]; poly-L/D-lactic acid [12]; polyvinyl alco- joint capsule was mobilized. The articular surface of the prox- hol hydrogel [13]), or partial/total metal joint arthroplasties imal phalanx was left intact. In the centre of the most promi- [14]. However, the clinical outcome and durability of these nent cartilage damage on MT-1 head a single, bi-phasic, bio- procedures is less predictable [15, 16]. degradable, osteochondral implant was positioned. The im- Due to an increasing awareness that subchondral bone res- plant diameters ranged from 7.5 mm (8 pts), 10 mm (10 toration is essential for high-quality durable cartilage repair, a pts), to 12.5 mm (2 pts). A designated surgical toolset was novel, aragonite-based, bi-phasic scaffold was developed used (CartiHeal, Israel) per the following surgical technique: (Agili-C™, CartiHeal) [17, 18]. The implant demonstrated (1) a guide wire positioning via a perpendicular aligner in the excellent preclinical results and has shown to enhance hyaline centre of MT-1 head, (2) a wire alignment along MT-1 shaft cartilage and subchondral bone restoration in the knee and additionally controlled using intra-operative radiographs, (3) ankle [19–21]. Herein, we present the results of a prospective, perpendicular drilling over the guide wire to the designated interventional, non-randomized, open-label, single-group as- depth in order to assure implant positioning 2 mm below the signment, multicenter clinical trial, with a follow-up of 24 articular surface, (4) a shaper that was used to adjust the lesion months in the MTPJ-1. We hypothesized that surgical treat- diameter, and (5) a gentle manual implant insertion with slight ment of hallux rigidus with this implant would be safe, signif- implant tapping to ensure press-fit fixation below the articular icantly decrease pain, increase range of motion in MTPJ-1, surface. Necessary concomitant osteotomy procedures were improve patients’ foot function, and demonstrate stable allowed, and they included seven extension osteotomies of repair-tissue formation over the implant. the proximal phalanx and one proximal MT-1 osteotomy for the realignment of the first ray. A case presentation with pre-/ intra-/post-operative details is presented in Fig. 1. Materials and methods Rehabilitation Study design Post-operatively, the operated toe was immobilized with a The study was designed as a prospective, interventional, non- soft-padded bandage for approximately two to three weeks.