ICRS 2019 - Conference Calendar

Browsing Over 343 Presentations

Extended Abstract (for invited Faculty only)

1.0.3 - Stem Cell Tourism - The Clinican' Perspective

Presentation Number
1.0.3
Lecture Time
12:30 - 12:45
Session Type
Plenary Session
Corresponding Author
Extended Abstract (for invited Faculty only) Stem Cells

1.0.2 - Stem Cell Tourism - The Scientist' Perspective

Presentation Number
1.0.2
Presentation Topic
Stem Cells
Lecture Time
12:15 - 12:30
Session Type
Plenary Session
Corresponding Author

Abstract

Introduction

As early as the 1700’s, it was observed that the potential of articular cartilage for intrinsic regeneration was minimal. Even very small cartilage defects cannot re-establish their essential low friction surface and tend to degrade further over time and a consequence of this inadequacy is osteoarthritis/OA, a chronic, degenerative joint disorder. Osteoarthritis is the fastest growing global health problem, with a total joint replacement being the only effective treatment for patients with end stage osteoarthritis. Many groups world-wide are examining the use of multiple stem cell/progenitor cells types to repair cartilage defects and/or modulate inflammation to promote healing in the osteoarthritic joint; however, little efficacy in promoting cartilage repair, or reducing patient symptoms over temporary treatments such as micro-fracture has been observed. One potential reason behind this lack of efficacy in clinical study results could be derived from the heterogeneity between patients, cell sources and even within cell populations (within a given patient) highlighting our need for more basic research into these progenitor and stem cell populations and their application in the treatment of osteoarthritis.

Content

Unfortunately this lack of evidence based research (both basic and clinical) has not stopped clinics from offering unfounded and unregulated cell therapies including ‘stem cell therapies’ for numerous chronic diseases. Many of the clinics that offer these services, target patients suffering from cartilage injury and/or osteoarthritis as there are currently no Health Canada or FDA approved therapeutics to treat this disease. While Health Canada has introduced a moratorium on these unapproved therapies and the FDA is pursuing injunctions against a number of clinics in the US, many clinics are still offered unfounded cell therapies to patients throughout North America.

At the present time, the limited amount of high quality published clinical research on these therapies, does not support the efficacy of these cell therapies for the treatment of osteoarthritis. In this presentation, I will discuss current cell therapies being offered as well the results of clinical and pre-clinical studies into the potential use of purified and characterized stem/progenitor cell populations for the treatment of cartilage injury and/or osteoarthritis.

While I believe that cell therapies including stem cell based approaches have promise for treating chronic degenerative conditions such as osteoarthritis, it is essential that we develop a better understanding of risks vs. benefits as well as the mechanisms underlying these therapies before they are offered to patients. Providing therapies not supported by strong basic and clinical evidence not only puts patients at risk, but may also irreparably damage the credibility of the field of regenerative medicine and our ability to translate evidence based therapies into the clinic.

Overall, as a field we require a deeper understanding of the role of tissue resident and exogenously delivered stem cells within the arthritic joint and base future cellular therapeutic approaches on a strong foundation of basic and pre-clinical science. Developing an effective disease-modifying therapy for osteoarthritis that uses patient-derived stem cells or that results in the patient’s own tissues repairing themselves would result in a paradigm shift in how precision medicine is utilized and delivered.

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Extended Abstract (for invited Faculty only)

1.0.1 - The Patient Perspective

Presentation Number
1.0.1
Lecture Time
12:00 - 12:15
Session Type
Plenary Session
Corresponding Author
Extended Abstract (for invited Faculty only) Others

1.0.4 - Discussion & Take Home Points

Presentation Number
1.0.4
Presentation Topic
Others
Lecture Time
12:45 - 13:00
Session Type
Plenary Session
Extended Abstract (for invited Faculty only) Others

2.0.1 - A Joint Effort: Clinical and Research Collaboration to Treat and Understand Knee Pathologies

Presentation Number
2.0.1
Presentation Topic
Others
Lecture Time
13:00 - 13:20
Session Type
Plenary Session
Corresponding Author

Abstract

Introduction

Knee pain effects 25% of individuals over age 55, and is most commonly due to osteoarthritis, although other etiologies can occur [1]. For many of these patients, their arthritis is too advanced for arthroscopy but too premature for arthroplasty. This leaves many patients in a grey zone where no good surgical treatments remain. Furthermore, even well indicated total knee arthroplasty outcomes result in persistent knee pain in 10-34% of cases [2]. Therefore, there is a large unmet need to help understand and treat knee pain outside of the structural abnormalities that is typically the focus for surgeons. Through collaborating with other medical fields and basic scientists, translational research can further our understanding, and eventually our treatment practices, of the knee in the future.

Content

The knee is a unique joint that may be better perceived as an organ due to its complexity and multiple tissue types and should be treated as such. When taking this approach, it becomes reasonable to focus treatments based on the different tissue types including the following: hyaline articular cartilage, bone, synovial fluid, meniscus, ligaments, and the synovial lining. Along with this, the contributions to pain can be significant when considering the bone and synovial lining as the cartilage is aneural. This was demonstrated by Dye et al. when he had an arthroscopy performed on his knee while awake and demonstrated that the most sensitive area was in fact the synovium [3]. Therefore, while treating structural abnormalities in the knee are important, treating the knee environment such as the synovial fluid and synovium itself can be just as relevant. These treatments can result from collaboration with the field of Rheumatology and have included treatments such as injections of steroids for post-traumatic osteoarthritis and IL1-Ra for ACL injury [4-5]. Novel injections are also being investigated, such as ABT-981, an immunoglobin that targets IL-1α and IL-1β and intraarticular injections of Etanercept [6].

Treatment options for patients with knee pathologies, both surgical and non-surgical, continue to evolve. This is largely in part due to a greater volume of basic and translational science literature of the knee, especially our understanding of the role of synovial fluid and the healing potential of cartilage. This understanding has led to a recent interest in the role of biologic treatments. Biologics, including adipose tissue, platelet-rich plasma, hyaluronic acid (HA), bone marrow aspiration (BMAC), and amniotic fluid, have been relatively understudied in the treatment of knee pain [7]. These compounds have the potential to alter the synovial fluid environment and may have a clinical benefit intraoperatively and postoperatively. Early evidence of their efficacy has been shown in some studies. For example, the AMELIA study, which investigated HA in knee arthritis, showed symptom improvement [8]. Other current clinical trials include the investigation of intraarticular BMAC for the treatment of early arthritis. As we continue researching these compounds, basic scientists must collaborate with physicians to understand the mechanism behind these interventions by testing the effects of biologics on an in vitro knee environment and exploring compounds, namely growth factors and cytokines, that likely play a role.

While different structures in the knee can cause pain, the nerves themselves can be the source of pain as well. For example, anesthesiologists have shown that the addition of cooled radiofrequency ablation with corticosteroid injection improves outcomes in patients with symptomatic osteoarthritis [9]. Furthermore, pain management physicians have shown that Botox can be used in the treatment of patellofemoral pain syndrome [10].

The components of the knee, from articular cartilage to synovium, create a unique environment that works as a synergistic unit. However, when parts of this system go awry, pain often ensues. Therefore, physicians from different specialties, researchers, physical therapists, and other healthcare personnel need to collaborate to understand and treat the pain of this complex joint.

References

[1] Peat, G., R. McCarney, and P. Croft. "Knee Pain and Osteoarthritis in Older Adults: A Review of Community Burden and Current Use of Primary Health Care." Ann Rheum Dis 60, no. 2 (Feb 2001): 91-7.

[2] Beswick, A. D., V. Wylde, R. Gooberman-Hill, A. Blom, and P. Dieppe. "What Proportion of Patients Report Long-Term Pain after Total Hip or Knee Replacement for Osteoarthritis? A Systematic Review of Prospective Studies in Unselected Patients." BMJ Open 2, no. 1 (2012): e000435.

[3] Dye, S. F., G. L. Vaupel, and C. C. Dye. "Conscious Neurosensory Mapping of the Internal Structures of the Human Knee without Intraarticular Anesthesia." Am J Sports Med 26, no. 6 (Nov-Dec 1998): 773-7.

[4] Kraus, V. B., J. Birmingham, T. V. Stabler, S. Feng, D. C. Taylor, C. T. Moorman, 3rd, W. E. Garrett, and A. P. Toth. "Effects of Intraarticular Il1-Ra for Acute Anterior Cruciate Ligament Knee Injury: A Randomized Controlled Pilot Trial (Nct00332254)." Osteoarthritis Cartilage 20, no. 4 (Apr 2012): 271-8.

[5] Lattermann, C., C. A. Jacobs, M. Proffitt Bunnell, L. J. Huston, L. G. Gammon, D. L. Johnson, E. K. Reinke, et al. "A Multicenter Study of Early Anti-Inflammatory Treatment in Patients with Acute Anterior Cruciate Ligament Tear." Am J Sports Med 45, no. 2 (Feb 2017): 325-33.

[6] Wang, S. X., S. B. Abramson, M. Attur, M. A. Karsdal, R. A. Preston, C. J. Lozada, M. P. Kosloski, et al. "Safety, Tolerability, and Pharmacodynamics of an Anti-Interleukin-1alpha/Beta Dual Variable Domain Immunoglobulin in Patients with Osteoarthritis of the Knee: A Randomized Phase 1 Study." Osteoarthritis Cartilage 25, no. 12 (Dec 2017): 1952-61.

[7] Devitt, B. M., S. W. Bell, K. E. Webster, J. A. Feller, and T. S. Whitehead. "Surgical Treatments of Cartilage Defects of the Knee: Systematic Review of Randomised Controlled Trials." Knee 24, no. 3 (Jun 2017): 508-17.

[8] Navarro-Sarabia, F., P. Coronel, E. Collantes, F. J. Navarro, A. R. de la Serna, A. Naranjo, M. Gimeno, G. Herrero-Beaumont, and Amelia study group. "A 40-Month Multicentre, Randomised Placebo-Controlled Study to Assess the Efficacy and Carry-over Effect of Repeated Intra-Articular Injections of Hyaluronic Acid in Knee Osteoarthritis: The Amelia Project." Ann Rheum Dis 70, no. 11 (Nov 2011): 1957-62.

[9] Davis, T., E. Loudermilk, M. DePalma, C. Hunter, D. Lindley, N. Patel, D. Choi, et al. "Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation with Corticosteroid Injection in the Management of Knee Pain from Osteoarthritis." Reg Anesth Pain Med 43, no. 1 (Jan 2018): 84-91.

[10] Chen, J. T., A. C. Tang, S. C. Lin, and S. F. Tang. "Anterior Knee Pain Caused by Patellofemoral Pain Syndrome Can Be Relieved by Botulinum Toxin Type a Injection." Clin Neurol Neurosurg 129 Suppl 1 (Feb 2015): S27-9.

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Extended Abstract (for invited Faculty only) Others

2.0.2 - Bridging the Bed-Bench Gap: Scientist Perspective

Presentation Number
2.0.2
Presentation Topic
Others
Lecture Time
13:20 - 13:40
Session Type
Plenary Session
Corresponding Author

Abstract

Introduction

It’s an exciting time for Orthoregeneration research. New tools and technologies have provided further insight into the biology and repair of joint tissues than ever before. Despite much progress in recent decades, the quest to achieve “perfect” joint restoration in patients with damaged cartilage has remained elusive. Perhaps the answer has been lost somewhere in translation. It is a long journey from bench to bedside, and this talk will explore why and how effective collaboration between basic scientists and physicians is essential to achieve our common goals.

Content

By definition, translational research leverages basic biology to create and implement practices which improve patient care [1]. Recent major advances in gene and cell therapy highlight how successful scientist-physician collaborations have resulted in ground-breaking therapies for patients [2, 3] and key examples exist in the cartilage repair field as well [4, 5]. A formidable obstacle to such partnerships is a perceived cultural divide between basic scientists and clinicians, which is not unique to the Orthoregeneration field [6]. This culture divide can often be attributed to communication barriers, and as highlighted by Restifo and Phelan, basic scientists and clinicians often do not speak the same language. [6] Lengthy and highly specialized training result in the creation of unique dialects including specific terminology and acronyms. These dialects separate not only the scientists and clinicians, but can alienate them from the general public as well. Where then, do we begin to bridge this divide? First, defining shared challenges and objectives is a critical step forward.

Fundamentally, both clinicians and basic scientists in our field are working to restore joint function. It is well understood from both perspectives that joints are complicated organs involving multiple tissues under varied stresses. However, there is less agreement regarding which specific challenges are the greatest in the field. At the bench, basic scientists have recently made great progress towards understanding signaling mechanisms required for maintenance of a healthy chrondrocyte phenotype [7]. We have new answers for long standing questions regarding the origin and fate of intrinsic joint progenitor cell populations [8-11]. If, how and when this information could be leveraged to develop new therapies for patients remains unknown. From a basic science perspective these are all intriguing areas of research – but which would be the highest priority for clinicians? Further communication is needed to develop a consensus.

Recent data suggests that the traditional linear pipeline from bench to bedside may not be the most efficient path forward [12]. Basic scientists in the Orthoregeneration field need a clear understanding of which issues clinicians view as the greatest challenges. Inversely, clinicians could benefit from information about the knowledge and tools available from the bench. A refined circular or iterative model of translational research which fosters greater reciprocal interaction between scientists and clinicians could be the most productive path forward towards these efforts [12]. Furthermore, this model should strive to include not only experts in the Orthoregeneration field, but interdisciplinary collaborations as well [13].

In summary, several key challenges exist for basic science – clinical collaborations. There is great strength in the diversity between scientists and clinicians. To leverage this strength, the Orthoregeneration field must work towards speaking a common language, collectively defining challenges so that we may work together to achieve shared goals.

References

1. Woolf, S.H., The meaning of translational research and why it matters. Jama, 2008. 299(2): p. 211-213.

2. Mendell, J.R., et al., Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med, 2017. 377(18): p. 1713-1722.

3. June, C.H., et al., CAR T cell immunotherapy for human cancer. Science, 2018. 359(6382): p. 1361-1365.

4. Grande, D.A., et al., The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. Journal of Orthopaedic Research, 1989. 7(2): p. 208-218.

5. Brittberg, M., et al., Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New england journal of medicine, 1994. 331(14): p. 889-895.

6. Restifo, L.L. and G.R. Phelan, The cultural divide: exploring communication barriers between scientists and clinicians. Disease models & mechanisms, 2011. 4(4): p. 423-426.

7. Sherwood, J., Osteoarthritis year in review 2018: biology. Osteoarthritis and Cartilage, 2019. 27(3): p. 365-370.

8. Li, L., et al., Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice. The FASEB Journal, 2016. 31(3): p. 1067-1084.

9. Decker, R.S., et al., Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs. Developmental Biology, 2017. 426(1): p. 56-68.

10. Roelofs, A.J., et al., Joint morphogenetic cells in the adult mammalian synovium. Nature Communications, 2017. 8: p. 15040.

11. Fellows, C.R., et al., Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence. Scientific reports, 2017. 7: p. 41421.

12. Fudge, N., et al., Optimising Translational Research Opportunities: A Systematic Review and Narrative Synthesis of Basic and Clinician Scientists' Perspectives of Factors Which Enable or Hinder Translational Research. PloS one, 2016. 11(8): p. e0160475-e0160475.

13. Chao, H.-T., L. Liu, and H.J. Bellen, Building dialogues between clinical and biomedical research through cross-species collaborations. Seminars in cell & developmental biology, 2017. 70: p. 49-57.

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Extended Abstract (for invited Faculty only) Others

2.0.3 - Innovating Joint Preservation - An Industry Perspective

Presentation Number
2.0.3
Presentation Topic
Others
Lecture Time
13:40 - 14:00
Session Type
Plenary Session
Corresponding Author

Abstract

Introduction

The cartilage repair field was the pioneer of biological approaches in the re-attainment of joint homeostasis, including the use of cells and tissue in joint surface repair. Why then are we still trying and failing to attain our goal whilst the rest of medicine surges ahead in harnessing the power of cells and genes in all areas of medicine from opthalmology to immunology and cancer? Was John Hunter correct in 1743?

Content

From the groundbreaking work of early pioneers in the cartilage repair field to the latest crop of therapies, we as a field are trying, and mostly not succeeding in our goal of repairing and regenerating cartilage. Cartilage repair pioneers led the way in understanding how cells and even tissues might be harvsted safely from living patients and stored or reused in the repair of cartilage defects.

This talk will explore the current state of the art in cell and gene therapies being developed globally for a variety of diseases and how the cartilage repair and joint preservation field might be able to learn from some of these developments and breakthroughs. The rapid expansion in the development of cell and gene therapies has allowed us to look at how therapies are developed and to make some fundamental changes to the way we think about collaboration between the various actors in this ecosystem. By starting with autologous products, we have brought the scientific, clinical and manufacturing steps much closer together with a common focus - the patient. This has allowed knowledge and experience to spill over from one group to the other, creating new ways of working to the benefit of our patients.

It is not just these groups that have had to change the way they work. Regulators, previously the keepers of the developmental and scientific application knowledge have had to lean into companies and academics in order to understand the rapidly developing field of Regenerative Medicine and the multitude of scientific adavnces being made at a blistering pace. By companies and academics assuming a new role of educators to the regulators, we have managed to build a much stronger relationship of trust with them and in so doing helped to advance their understanding, but also our ability to propose new approaches and therapies at a much faster rate with more uncertainties than previously before. By bringing the regulators on our journey of scientific discovery, we have empowered them to generally take a more risk balanced approach to regulation and review of advanced therapies, allowing patients to access them sooner than previously.

The relationship between academia and industry has also shifted thanks to the unique challenges of advanced therapies. No longer are the large pharma giants the masters of drug discovery and development. They have come to realise that the true innovation engines are in academia. Academia is the fertile ground of scientific breakthrough, but industry is the sunlight that allows it to blossom into therapies from which thousands of patients will benefit. Regen med has allowed industry and academia to find new ways of innovating in partnership. We will explore some of these examples and how patients have benefitted from this new found mutual understanding and respect.

Only by all players in the ecosystem working together to innovate for patients will we be able to improve how we address the challenges of repairing and regenerating the joint, and soon perhaps even preventing the degeneration occuring in the first place. This is an exciting time for our ecosystem and only by collaborating will we truly prove John Hunter wrong.

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Extended Abstract (for invited Faculty only) Rehabilitation and Sport

3.2.1 - Prevention Strategies: Current Trends & Knowledge Using the Experiences of ACL Research

Presentation Number
3.2.1
Presentation Topic
Rehabilitation and Sport
Lecture Time
14:15 - 14:35
Session Type
Special Session
Corresponding Author

Abstract

Introduction

Knee injuries are a common occurrence of sport participation and it has become increasing apparent that such injuries can have a lifelong consequence for the athlete. One of the most serious knee injuries is an anterior cruciate ligament (ACL) tear and this injury will be used throughout this talk to illustrate concepts pertaining to injury prevention or risk reduction.

Content

There is evidence to show that degenerative changes in the knee can occur early, within one to two years, after an anterior cruciate ligament (ACL) injury and that on average 50% of patients are estimated to develop disabling osteoarthritis in the longer term. Although there is some evidence that ACL reconstruction reduces the risk of osteoarthritis there is stronger evidence that it does little to protect the knee from long term degeneration. Associated damage which may occur to the menisci or articular surfaces, has also been shown to increase the risk of developing osteoarthritis. Therefore, injury prevention is key. Unfortunately, the rates of ACL injury are steadily increasing, particularly at the younger end of the age spectrum. Concerning new data also shows that rates of concomitant meniscal injuries have also substantially increased, and again the younger aged athlete is more susceptible. This increasing prevalence of meniscal involvement is of concern for long term knee health.

Fortunately, injury prevention programs can reduce the risk of both knee injuries and ACL injuries. Most programs have targeted female athletes and incorporate neuromuscular training interventions to address modifiable risk factors. Most evidence is available for ACL injury risk reduction in female athletes although there is emerging evidence for male athletes. It has been recommended that such programs should include a combination of plyometric, strength and balance training for at least 6 weeks with a minimum of 1 session per week. For optimal results training should take place both pre and in-season. Critical components for the success of such training programs have been shown to be age (younger athletes gaining most benefit), dosage (superior results with longer and more frequent training), exercise variation and verbal feedback. Including any one of these four components has been shown to reduce injury risk by 18%. Injury prevention programs additionally have the potential to reduce further medical costs, with cost analysis showing that the optimum implementation strategy is to target high risk athletes aged 12-25 years. For this group US$17,000 can be spent per participant on the program. However, perhaps one of the biggest challenges with injury prevention training programs is in their implementation. Regular compliance is a critical factor for injury risk reduction and barriers to high compliance have been therefore been investigated. Program design has been shown to be a key influencing factor with programs that contain sport specific tasks and less than 15 minutes to complete positively associated with compliance.

Despite bests efforts to reduce ACL injury risk, ACL injuries still occur, and attention must also be directed to secondary prevention strategies. These include prevention of further ACL injury as well as prevention of post traumatic knee osteoarthritis. In terms of second ACL injury prevention, although numerous risk factors have been identified it is clear that younger athletes who return to pivot and contact sports have high rates of further injury and must therefore be a focus. Return to sport testing has become popular over recent years. It is unclear though whether such testing is designed to determine whether an athlete is capable of returning to sport or determine whether it is safe. Despite the current discussions around return to sport testing following ACL reconstruction, the evidence around it is relatively limited, and the available evidence is somewhat conflicting. A common theme however is that a surprisingly low number of athletes meet return to sport thresholds and criteria with a recent systematic review showing an overall rate of 23% of patients passing return to sport test batteries both prior to and after return to strenuous sports. Caution should therefore be used in applying information gained from current return to sport testing and advising athletes about the risk for further injury.

It has recently been argued that there is no clear evi­dence that current ACL rehabilitation programs include approaches to prevent future de­velopment of knee osteoarthritis and that such an approach should include aggressive knee extensor strengthening, as well as strategies for optimal loading of the vulnerable joint. Patient education should also be a key component to ensure realistic expectations for long term knee heath.

Whilst injury prevention and risk reduction strategies for primary and secondary ACL injury and osteoarthritis has been a focus of current research the challenge remains to extrapolate from this body of evidence to other lower limb musculoskeletal injuries for which data is scarce.

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Extended Abstract (for invited Faculty only) Rehabilitation and Sport

3.2.2 - Does Blood Flow Restriction have a Role?

Presentation Number
3.2.2
Presentation Topic
Rehabilitation and Sport
Lecture Time
14:35 - 14:55
Session Type
Special Session
Corresponding Author

Abstract

Introduction

Marked quadriceps weakness has been demonstrated prior to undergoing cartilage restoration procedures, and these deficits often persist postoperatively. Blood flow restriction training (BFRT) continues to gain interest amongst rehabilitation specialists as a novel method to improve quadriceps strength. Blood flow restriction training (BFRT) involves the use of an inflatable cuff applied to the thigh to slow blood flow as subjects exercise with a light weight allowing them to receive the same training benefits as if they were training under high loads. The premise for using BFRT after cartilage procedures was initially based off successful use in healthy populations but more recently in patients knee disorders demonstrating greater strength gains than traditional forms of exercise. There is evidence supporting the premise that BFRT will result in both improved quadriceps and hip strength. This then holds promise as greater muscle strength in turn will result in improved lower extremity biomechanics, improved functional capacity, and an accelerated recovery.

Content

In this presentation, we will discuss the physiologic mechanisms of BFRT. We and others have shown BFRT is able to preferentially improve muscle fiber cross-sectional area, increase satellite cell proliferation and may reduce the extracellular matrix in healthy subjects. We are further motivated by our recently published data in anterior cruciate ligament reconstructed subjects which show that these are the precise properties of muscle that are negatively impacted after the injury and rehabilitation so should be positively altered by BFRT.We have also seen that improved quadriceps strength is associated with reducedfear of re-injury and improved self-reported ability to perform quadriceps-dominant activities such as ascending stairs.

BFRT could potentially benefit those with patellofemoral lesions as well. Increased quadriceps strength has been shown to be protective against patellofemoral cartilage loss as well as less pain and improved function.BFRT may not only result in improved quadriceps strength but also proximal changes in hip strength and muscular characteristics. Hip weakness and increased knee adduction angles increase the forces born by the articular cartilage. Improving quadriceps and hip strength may also be chondroprotective by reducing femoral internal rotation thereby lessening compressive forces borne by the cartilage of the lateral patella and trochlea. BFRT with the cuff placed around the proximal thigh has been demonstrated to improve quadriceps strength but has also resulted in changes proximal to the cuff. In healthy volunteers, thigh girth and hip abduction and external rotation strength have both been shown to have significantly greater improvements following a BFRT program when compared to those that completed the same exercise program without BFRT. In older adults, BFRT has also been demonstrated to increase cross sectional area of the hip adductor and gluteus maximus muscle groups in addition to the quadriceps.

Despite rapid adoption in the clinical setting, there is a great deal of variability in BFRT treatment protocols being used. This variability then results in variable strength gains with BFRT. In a balanced presentation of the literature to date, we will also discuss the treatment protocols that have been the most effective as well as contraindications that must be considered prior to using BFRT.

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Extended Abstract (for invited Faculty only)

3.2.3 - Can we Accelerate Rehab?

Presentation Number
3.2.3
Lecture Time
14:55 - 15:15
Session Type
Special Session
Corresponding Author
Extended Abstract (for invited Faculty only)

3.3.1 - Neocart

Presentation Number
3.3.1
Lecture Time
14:15 - 14:35
Session Type
Special Session
Corresponding Author
Disclosure
No Significant Commercial Relationship
Extended Abstract (for invited Faculty only) Cartilage /Cell Transplantation

3.3.2 - Prospective, Randomized Trial to Compare Autologous Chondrocyte Implantation with Spheroid Technology vs. Microfracture

Presentation Number
3.3.2
Presentation Topic
Cartilage /Cell Transplantation
Lecture Time
14:35 - 14:55
Session Type
Special Session
Corresponding Author

Abstract

Introduction

Introducation: Matrix-associated autologous chondrocyte implantation (ACI) and microfracture (MF) are well-established treatments for full-thickness cartilage defects of the knee. However, clinical studies of high-level evidence comparing matrix-associated ACI to MF are still limited. Additionally, since different products and principles of ACI vary significantly, there is a specific need for clinical evidence in terms of efficiency and safety for every individual approach. With regard to this, the present prospective randomized clinical trial was initiated to investigate confirm the non-inferiority and investigate the superiority of a pure autologous spheroid based ACI (SPHEROX TM) compared with microfracture by a statistical hierarchical approach for focal and isolated cartilage defects of the knee op to a defect size of 2 cm2.

Content

Methods: Patients with focal cartilage defects of the knee between 1 and 4 cm2 were randomized to be treated by ACI or microfracture. No concomitant procedures were included. Both procedures followed standard protocols. In short, at time of screening arthroscopy the availability of the patients for the present study was confirmed and the patient was randomizend in either the ACI group or the microfracture group. While microfracturing was performed immediately in this group, for the ACI group cell harvesting was performed during index arthroscopy followed by the expansion period of approximately 8 weeks. In the ACI group, the transplantation was performed as a second surgery in a mini-open approach. For the ACI 10–70 spheroids/cm2 were administered. Rehabilitation was similar in both group. In short, partial weight bearing was recommended for a period of 8 weeks and limited range of motion was recommended in preference of the individual surgeon. CPM was used routinely. The primary outcome measure was the Knee Injury and Osteoarthritis Outcome Score (KOOS) at the time of surgery and 6,12, 24 and 36 months following index surgery. This report presents results for 24 and 36 months after treatment.

Results: Both ACI and microfracture led to a significant improvement treated over the three-year observation period. For the overall KOOS, the statistical hypothesis of non-inferiority (the intended primary goal of the study) was formally confirmed; additionally, for the three subscores “Quality of Life”, “Activities of daily living” and “Sport and Recreation”, superiority of the ACI over MF was shown at different timepoints during the follow-up period. Occurrence of adverse events were not different between both treatments (ACI 77%; MF 74%). Concerning patient's safety, 9 Serious adverse events were reported for ACI and 10 for MF. However, none of the SAE was considered treatment related in the ACI group, while in the MF group 5 were possible treatment related.

Conclusion: Patients treated with matrix-associated ACI with spheroid technology showed substantial improvement in various clinical outcomes after 36 months. The advantage of ACI compared with microfracture was underlined by the clear, formal demonstration of its statistical non-inferiority, approaching superiority, and by (descriptive) superiority in the KOOS subscores ‘Activities of daily living’ and ‘Sport/Recreation’. Age and defect size showed no significant effect on clinical outcome, indicating that the treatment of limited focal defects – i.e., smaller than currently recommended by national and international orthopedic societies – should be considered.

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