Person: Gomoll, Andreas H.
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Gomoll
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Andreas H.
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Gomoll, Andreas H.
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Publication Cell Seeding Densities in Autologous Chondrocyte Implantation Techniques for Cartilage Repair(SAGE Publications, 2012) Foldager, Casper Bindzus; Gomoll, Andreas H.; Lind, Martin; Spector, MyronCartilage repair techniques have been among the most intensively investigated treatments in orthopedics for the past decade, and several different treatment modalities are currently available. Despite the extensive research effort within this field, the generation of hyaline cartilage remains a considerable challenge. There are many parameters attendant to each of the cartilage repair techniques that can affect the amount and types of reparative tissue generated in the cartilage defect, and some of the most fundamental of these parameters have yet to be fully investigated. For procedures in which in vitro–cultured autologous chondrocytes are implanted under a periosteal or synthetic membrane cover, or seeded onto a porous membrane or scaffold, little is known about how the number of cells affects the clinical outcome. Few published clinical studies address the cell seeding density that was employed. The principal objective of this review is to provide an overview of the cell seeding densities used in cell-based treatments currently available in the clinic for cartilage repair. Select preclinical studies that have informed the use of specific cell seeding densities in the clinic are also discussed.Publication Surgical and Functional Outcomes in Patients Undergoing Total Knee Replacement With Patient-Specific Implants Compared With “Off-the-Shelf” Implants(SAGE Publications, 2015) Schwarzkopf, Ran; Brodsky, Merrick; Garcia, Giancarlo A.; Gomoll, Andreas H.Background: Total knee arthroplasty (TKA) instrumentation and implant designs have been evolving, with one of the current innovations being patient-specific implants (PSIs). Purpose To evaluate whether there is a significant difference in surgical time, intraoperative blood loss, postoperative range of motion, and length of stay between PSI and conventional TKA. Study Design Cohort study; Level of evidence, 3. Methods: A consecutive series of 621 TKA patients, 307 with PSIs and 314 with conventional implants, was reviewed. Differences in estimated blood loss, length of stay, range of motion, and surgical time/tourniquet time between the 2 cohorts were analyzed. Results: Linear regression analysis demonstrated that PSI decreased estimated blood loss by 44.72 mL (P < .01), decreased length of stay by 0.39 days (P < .01), decreased postoperative range of motion by 3.90° (P < .01), and had a negligible difference on surgical and tourniquet time. Conclusion: The use of PSI is associated with decreased estimated blood loss, decreased length of stay, decreased range of motion, and no discernible difference in surgical or tourniquet time, all of which are unlikely to be clinically significant.Publication Aarhus Regenerative Orthopaedics Symposium (AROS): Regeneration in the ageing population(Taylor & Francis, 2017) Foldager, Casper B; Bendtsen, Michael; Berg, Lise C; Brinchmann, Jan E; Brittberg, Mats; Bunger, Cody; Canseco, Jose; Chen, Li; Christensen, Bjørn B; Colombier, Pauline; Deleuran, Bent W; Edwards, James; Elmengaard, Brian; Farr, Jack; Gatenholm, Birgitta; Gomoll, Andreas H.; Hui, James H; Jakobsen, Rune B; Joergensen, Natasja L; Kassem, Moustapha; Koch, Thomas; Kold, Søren; Krogsgaard, Michael R; Lauridsen, Henrik; Le, Dang; Le Visage, Catherine; Lind, Martin; Nygaard, Jens V; Olesen, Morten L; Pedersen, Michael; Rathcke, Martin; Richardson, James B; Roberts, Sally; Rölfing, Jan H D; Sakai, Daisuke; Toh, Wei Seong; Urban, Jill; Spector, MyronThe combination of modern interventional and preventive medicine has led to an epidemic of ageing. While this phenomenon is a positive consequence of an improved lifestyle and achievements in a society, the longer life expectancy is often accompanied by decline in quality of life due to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal, patient-related, and basic science-related challenges in order to provide a reasoned roadmap for the future to deal with this compelling and urgent healthcare problem.Publication Cartilage repair in the degenerative ageing knee: A narrative review and analysis(Taylor & Francis, 2016) Brittberg, Mats; Gomoll, Andreas H.; Canseco, José A; Far, Jack; Lind, Martin; Hui, JamesBackground and purpose Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints.Publication Cellular senescence in aging and osteoarthritis: Implications for cartilage repair(Taylor & Francis, 2016) Toh, Wei Seong; Brittberg, Mats; Farr, Jack; Foldager, Casper Bindzus; Gomoll, Andreas H.; Hui, James Hoi Po; Richardson, James B; Roberts, Sally; Spector, MyronIt is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. The underlying mechanisms of cellular senescence, while not fully understood, have been associated with telomere erosion, DNA damage, oxidative stress, and inflammation. In this review, we discuss the causes and consequences of cellular senescence, and the associated biological challenges in cartilage repair. In addition, we present novel strategies for modulation of cellular senescence that may help to improve cartilage regeneration in an aging population.Publication Collagen Type IV and Laminin Expressions during Cartilage Repair and in Late Clinically Failed Repair Tissues from Human Subjects(SAGE Publications, 2015) Foldager, Casper Bindzus; Toh, Wei Seong; Christensen, Bjørn Borsøe; Lind, Martin; Gomoll, Andreas H.; Spector, MyronObjective: To identify the collagen type IV (Col4) isoform in articular cartilage and to evaluate the expressions of Col4 and laminin in the pericellular matrix (PCM) in damaged cartilage and during cartilage repair. Design: The Col4 isoform was determined in chondrocytes isolated from 6 patients cultured up to 6 days and in 21% O2 or 1% O2, and the gene expression of Col4 α-chains was investigated. The distribution of Col4 and laminin in traumatically damaged cartilage (n = 7) and clinically failed cartilage repair (microfracture, TruFit, autologous chondrocyte implantation; n = 11) were investigated using immunohistochemistry. Normal human cartilage was used as control (n = 8). The distribution during clinical cartilage repair procedures was investigated in a minipig model with 6-month follow-up (untreated chondral, untreated osteochondral, microfracture, autologous chondrocyte implantation; n = 10). Results: The Col4 isoform in articular cartilage was characterized as α1α1α2, which is an isoform containing antiangiogenic domains in the NC1-terminals (arresten and canstatin). In normal cartilage, laminin and Col4 was exclusively found in the PCM. High amounts (>50%) of Col4 in the PCM significantly decreased in damaged cartilage (P = 0.004) and clinically failed repair tissue (P < 0.001). Laminin was only found with high expression (>50%) in 4/8 of the normal samples, which was not statistically significantly different from damaged cartilage (P = 0.15) or failed cartilage repair (P = 0.054). Conclusions: Col4 in cartilage contain antiangiogenic domains and may play a role in the hypoxic environment in articular cartilage. Col4 and laminin was not found in the PCM of damaged and clinically failed repair.Publication Outcomes of Ultrasound-guided Glen Humeral Corticosteroid Injections in Adhesive Capsulitis(2016) Song, Amos; Katz, Jeffrey; Higgins, Laurence D; Newman, Joel; Gomoll, Andreas H.; Jain, Nitin B.Aims To assess short and longer-term outcomes of ultrasound-guided glenohumeral corticosteroid injections for adhesive capsulitis. Study Design A mixed prospective and retrospective study design Place and Duration of Study Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Department of Orthopaedic Surgery, Brigham and Women’s Hospital, between June 2011 and July 2012. Methodology Using medical records, we first retrospectively identified patients who had received ultrasound-guided injections of lidocaine and triamcinolone for adhesive capsulitis We then assessed short-term follow-up outcomes (within 3 months of procedure) using medical record review and phone interviews. Longer-term follow-up (at least 3 months from the procedure) outcomes were determined by mailings and phone calls. Average and worst shoulder pain scores were measured on a visual analog scale. Shoulder ROM was measured in forward flexion, isolated abduction, and external rotation. Results: Patients presented an average of 5.1 (SD=4.1) months after onset of symptoms. Within three months of the injection, 55.9% (95% CI: 39.2%, 72.6%) of patients reported greater than 75% pain relief and 44.1% (95% CI: 27.4%, 60.8%) of patients reported greater than 75% ROM improvement. The percentage of patients who improved increased with increased duration of follow-up. At short-term follow-up (mean=2.1 months, SD=2.7), average pain decreased from 5.6 (SD=2.2) to 3.0 (SD=1.8) (p ≤ .001) and worst pain decreased from 7.8 (SD=1.2) to 4.3 (SD=3.2) (p ≤ .001). At longer-term follow-up (mean =10.4 months, SD=3.7), average pain decreased to 1.9 (SD=1.9) (p ≤ .001) and worst pain decreased to 2.9 (SD=2.3) (p ≤ .001). Conclusion: A majority of patients had significant pain reduction and functional improvement after an ultrasound guided glenohumeral corticosteroid injection for adhesive capsulitis. Our patients experience the majority of their pain and functional relief within the first three months after an ultrasound-guided corticosteroid injection with continued increase in relief in the longer-term.Publication Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues(SAGE Publications, 2014) Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, MyronObjective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM.Publication Biomechanical Considerations in the Pathogenesis of Osteoarthritis of the Knee(Springer-Verlag, 2011) Heijink, Andras; Gomoll, Andreas H.; Madry, Henning; Drobnič, Matej; Filardo, Giuseppe; Espregueira-Mendes, João; Van Dijk, C. NiekOsteoarthritis is the most common joint disease and a major cause of disability. The knee is the large joint most affected. While chronological age is the single most important risk factor of osteoarthritis, the pathogenesis of knee osteoarthritis in the young patient is predominantly related to an unfavorable biomechanical environment at the joint. This results in mechanical demand that exceeds the ability of a joint to repair and maintain itself, predisposing the articular cartilage to premature degeneration. This review examines the available basic science, preclinical and clinical evidence regarding several such unfavorable biomechanical conditions about the knee: malalignment, loss of meniscal tissue, cartilage defects and joint instability or laxity.Publication Serum Levels of Hyaluronic Acid and Chondroitin Sulfate as a Non-Invasive Method to Evaluate Healing after Cartilage Repair Procedures(BioMed Central, 2009) Gomoll, Andreas H.Magnetic resonance imaging remains the only non-invasive method to assess the quality of cartilage repair procedures, but ideally would be complemented by other modalities, particularly blood tests. Nganvongpanit and colleagues investigated serum levels of hyaluronic acid (HA) and chondroitin sulfate (CS) for their correlation with tissue quality after cartilage repair with autologous chondrocytes versus subchondral drilling in a dog model. They reported better tissue quality in animals treated with chondrocyte implantation. Serum levels correlated with the histological score of biopsy samples: CS showed a negative (r = -0.69) and HA a positive (r = +0.46) correlation. Many questions remain to be answered before serum markers can provide a reliable, non-invasive tool to assess tissue quality, but these data provide an important foundation for additional research.