A Combination of Tisseel Fibrin Glue and Orthokine ACS improves Knee Meniscus Injury Treatment and helps Avoid Surgery 4-year follow-up Archive Study

Background: The routine use of biological therapies with potentially regenerative augmentation of tissue repair is reality. Techniques applied include stem cells, platelet preparations, recombinant growth factors and autologous conditioned serum (ACS), partly in combination with other techniques such as matrices, surgery and fibrin glue. ACS contains blood cell released factors which have the potential to improve tissue repair or regeneration. Aim: Retrospective analysis of clinical data of intra-articular fibrin glue fixation combined with ACS injections in clinical cases of routine outpatients presenting with knee pain and MRIconfirmed meniscal defects. Methods: An established intra-articular injection treatment method for osteoarthritis involving autologous conditioned serum (ACS) was routinely employed. ACS is prepared from patient’s blood subjected to extended coagulation at physiologic temperature. The serum supernatant is separated from cellular components by centrifugation. A dedicated medical device (EOT®II, Orthokine) is employed. Outpatients (n = 170), with lesions of the knee meniscus of heterogeneous genesis, severity and duration, were treated with fibrin glue to fixate the tissue injury followed by weekly intra-articular ACS injections (up to 6). Average age was 55.29 years (SD ±12.48) (range 14-84). Follow ups extend from baseline up to 4 years. Clinical effects are documented by WOMAC score at baseline, 6 weeks and yearly intervals. All analyses were performed from archived patient files. Results: 8 of 170 patients chose surgical treatment of the meniscal injury. 162 patients avoided surgery during the period analyzed. Mean WOMAC global score improved from 34.62 (SD ± 18.48) to 13.18 (SD ± 9.52) (p = 0.0015) at 4 years. Conclusion: This archive evaluation of a heterogeneous real-life cohort suggests that intraarticular fixation of meniscus injuries with fibrin glue followed by 4 i.a. ACS/BCS injections improves knee symptoms associated with meniscal injury. Controlled studies of Fibrin Glue + ACS treatment for meniscal lesions are advocated. Sports Injuries & Medicine Strumper RW, et al. Sports Injr Med: 5: 172. www.doi. org/10.29011/2576-9596.100072 www.gavinpublishers. com Citation: Strümper RW, Reinecke J, Rechmeier JW, Schilling R, Wehling P (2021) A Combination of Tisseel Fibrin Glue and Orthokine ACS improves Knee Meniscus Injury Treatment and helps Avoid Surgery 4-year follow-up Archive Study. Sports Injr Med 10172. DOI: 10.29011/2576-9596.110172 2 Volume 5; Issue 01 Sports Injr Med, an open access journal ISSN: 2576-9596 Introduction Knee injury is a major risk factor for the development of knee OA. The OA risk after knee injury goes up 4-6fold [1]. Numbers of acute meniscus injuries per 1000 inhabitants per year range from 0.5 to 0.7. This relates to stable knees. Instable knees’ percentage goes up to 96 % depending on the case. Meniscal tears are a common knee injury often related to sports activities. Among US high school athletes more than 20 % of all knee injuries are meniscus injuries. Other publications looking at different cohorts find > 10 % rates [2,3]. Knee injuries in general are significantly more likely to be treated with surgery than all other injuries. Hence, most meniscal injuries tend also to be treated surgically (> 60 %) [4]. Interestingly [2] points out that a vast number of sports injuries may not be treated appropriately. Since then (2000) this may have improved, advanced imaging techniques have improved in quality and become more easily accessible [5]. The 2019 ESSKA meniscus consensus [6] recommends surgery as early as possible when repair is required, preservation of the meniscus being the main intention of therapy by surgical repair. Biological augmentation (e.g. ACS, PRP, Stem Cells) was not embraced for lack of consistent evidence. Nonetheless ESSKA published an Instructional Course Lecture Book featuring a chapter on Biological Therapies in Orthopedics and Sports Medicine [7]. This emphasizes the fact that there is high interest in biologically augmented meniscus repair. Preservation of the meniscus has been attempted with locally applied fibrin glue [8]. Limited evidence exists for the use of autologous fibrin clots [9, 10]. However, these techniques have not been widely adapted in the clinical community. Fibrin glue stability as a “cast” is limited to weeks and the clinical results obviously were not convincing. Autologous conditioned serum in meniscal tears We have described a technique using autologous conditioned serum (ACS) also known as blood cell secretome (BCS) as augmentation to improve symptoms and structural damage related to meniscal tears without prior or concomitant surgery. Oxford knee score (OKS) and Boston Leeds Osteoarthritis Knee Score (BLOKS) were applied in 47 outpatients and documented significant improvements for both scores [11]. Other studies have shown the efficacy of BCS mostly in Osteoarthritis but also in Tendon and Muscle healing (soft tissue) (XXX). ACS/ BCS efficacy in Back pain resulting either from Facet OA or nerve root inflammation has also been published (XXX). Autologous conditioned serum combined with fibrin glue in meniscal tears In our office so far a total of > 500 cases of injured knee menisci have been treated routinely with fibrin glue locally applied by MRI guidance. Subsequently patients received ± 4 injections with ACS in weekly succession. The rationale of this protocol is that Fibrin glue is able to fixate the meniscal wound, bringing the margins in close vicinity. Similar to arthroscopic suturing or pin fixation this aims at facilitating cellular healing. In a damaged joint the milieu often is inflammatory/catabolic. Augmentation with ACS/BCS has shown to be inflammation resolving, to improve healing in a number of experimental and clinical studies with degenerative and acute tissue injuries. It should be capable to support healing more efficiently if the margins of a meniscal wound are kept in close contact long enough to enable cellular contact/healing and junction. This procedure was performed in a setting that avoids anesthesia and surgery. It may be suitable for a subset of injuries where surgical intervention is not strictly necessary. Materials and Methods Patients Outpatient files with a diagnosis of meniscal lesions who had undergone Tisseel plus Orthokine BCS treatment were included in this archive study. All patients had pain, effusion and loss of function of the index knee before treatment. Data were obtained in compliance with German law and the Declaration of Helsinki, and the authorized ethical committee cleared this retrospective study (U1111-1268-5097, No 276/2021) for the period 2016-2020. Patient anonymity has been carefully protected in the analysis and data analysis. This study meets the ethical standards of the journal. 170 cases of which full score documentation were available and included in this analysis. ACS/BCS ACS/BCS was prepared with venous blood drawn with the Orthokine device (EOT®II-syringe, Orthogen Lab Services, Germany), which contains medical grade glass spheres. Patients’ blood was subjected to extended coagulation in the device for 6 hours at 37 ° C. Serum was then recovered by centrifugation and injected into the patient’ joints at weekly intervals. The conditioned, cell-free serum is rich in Growth Factors IGF, TGFb, EGF, FGF, PDGF and Cytokines IL-1Ra and smaller amounts of IL-1b, IL-6, TNFa [33].