ICRS 2018 - Conference Calendar

Found 536 Presentations For Request "primate"

Podium Presentation Rehabilitation and Sport

15.4.1 - 10 Year Follow-Up of a Randomized Trial Evaluating Accelerated Weight Bearing after Autologous Chondrocyte Implantation (ID 9387)

Presentation Number
15.4.1
Topic
Rehabilitation and Sport
Lecture Time
17:00 - 17:09
Corresponding Author
Disclosure
J Ebert - Grant Research Support (Hollywood Private Hospital Research Foundation)

Abstract

Purpose

Encouraging outcomes are reported following matrix-induced autologous chondrocyte implantation (MACI), though longer term results are lacking and rehabilitation is traditionally conservative. This study investigated long-term outcomes after an accelerated weight bearing (WB) protocol.

Methods and Materials

After MACI, 70 patients were randomized to an accelerated (AR, 8 weeks, n=34) or conservative (CR, 12 weeks, n=36) return to full WB gait. Clinical outcomes were assessed at 3 and 6 months, as well as 1, 2, 5 and 10 years (range 10.5-11.5 years). This included a range of outcome measures including the KOOS, Lysholm, Cincinnati, Tegner and SF-36, as well as active knee ROM and maximal isokinetic knee strength. High resolution magnetic resonance imaging (MRI) was undertaken at 3 months and 1, 2, 5 and 10 years to assess pertinent parameters of graft repair, as well as a combined MRI composite score. ANOVA investigated all scores over time, between the AR and CR groups.

Results

No group differences (p>0.05) were observed in clinical or MRI-based scores. All clinical scores significantly improved (p<0.001) to 5 years, maintained to 10 years. At 10 years post-surgery, a mean Limb Symmetry Index (LSI) for maximal knee extension strength was calculated for the AR (94.9%) and CR (98.9%) groups, comparing the operated and non-operated limbs. 79.4% of the AR group and 83.3% of the CR group had good-excellent tissue infill, while a good-excellent composite score was observed in 82.4% of AR and 83.3% of CR patients. MRI demonstrated graft failure in 8.8% (AR, n=3) and 8.3% (CR, n=3) of patients. 88.2% (AR) and 88.9% (CR) were satisfied with MACI for relieving their pain.

Conclusion

MACI provided high levels of satisfaction and tissue durability beyond 10 years. The AR protocol reduced the time spent on crutches and produced comparable outcomes to the conservative regimen, without compromising graft integrity.

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Podium Presentation Rehabilitation and Sport

15.4.7 - Return To Running Following Knee Osteochondral Repair Using An Anti-Gravity Treadmill (ID 9388)

Presentation Number
15.4.7
Topic
Rehabilitation and Sport
Lecture Time
17:54 - 18:03
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

The purpose of this study was to assess the impact of an anti-gravity treadmill return to running programme on self-efficacy and subjective knee function following knee osteochondral surgery.

Methods and Materials

Two otherwise healthy female endurance runners who had undergone knee osteochondral surgery were recruited. Patient A was 9 months post-surgery for a left knee femoral cartilage grade 3-4 defect 3 cm 2. Patient B was 11 weeks post-surgery for a partial lateral menisectomy and chondroplasty. An anti-gravity treadmill was used to manipulate loading during a graduated phased return to running. Self-efficacy was evaluated using the Self-Efficacy for Rehabilitation outcomes scale (SER) and the Knee Self-Efficacy Scale (K-SES). Subjective knee function was evaluated using the Knee injury and Osteoarthritis Outcome Score (KOOS).

Results

The programmes resulted in improvements in SER (Patient A 57%; Patient B 18%) and K-SES present (Patient A 89%; Patient B 33%) and K-SES future (Patient A 65%; Patient B 33%). Only the KOOS Sport/Rec (Patient A and B) and the Quality of Life (Patient B) subscales showed clinically important improvements.

Conclusion

The programmes resulted in improved knee and rehabilitation self-efficacy and subjective knee function following osteochondral repair of the knee. These case reports illustrate the importance of considering self-efficacy in individualising rehabilitation after knee osteochondral surgery and highlights the potential role for anti-gravity treadmills in enhancing self-efficacy and subjective knee function in preparation for a return to sport.

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P242 - Current Trends In The Publication Of Articular Cartilage Repair Techniques (ID 9392)

Presentation Number
P242
Topic
Others
Lecture Time
10:45 - 10:45
Session Name
11.0 - Poster Viewing / Exhibition (ID 780)
Corresponding Author
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

Articular cartilage lesions are difficult to heal, and remain a challenge for orthopedic surgeons. Many techniques are now being used for cartilage repair; including abrasion, drilling, microfracture, autologous osteochondral transplantation, allografts and autologous chondrocyte implantation(ACI) either as two-staged or a single-stage procedure. The field is thus evolving, with established and emerging technologies.Here, we aim to study the publication trends in articular cartilage repair over the last ten years.

Methods and Materials

A literature search was performed on the Pubmed, Web of Science, and SCOPUS databases.Suitable key words and Boolean operators were used (articular cartilage injury AND ‘‘marrow stimulation OR microfracture’’, “osteochondral autograft,” “osteochondral allograft” and “‘autologous chondrocyte implantation”), in September 2017. Trends in a publication on these topics were analyzed, focussing on a number of publications over last ten years, type of research (basic science or clinical), type of publication (the language of publication, authors, institution, and country.

Results

articular cartilage repair-country-institution-author.pngarticular cartilage repair articles-year.pngThere was an increasing trend in publications related to articular cartilage repair.A search on Pubmed revealed 407,115,112 and 303 documents on searching for articular cartilage injury AND “marrow stimulation OR microfracture,” “osteochondral autograft,” “osteochondral allograft,” and ACI respectively.Similar searches revealed 5804,59,70 and 373 documents on Web of Science; 5310,1601,1692 and 3926 on SCOPUS respectively, in the same order of topics.We manually excluded unrelated articles and publication trends were analyzed. Overall, most papers published were from the United States, and Cole BJ was the most published author.

Conclusion

There has been an upsurge of interest in articular cartilage repair techniques, as is evident by an increasing trend in research and publications in this area.Two stage procedures of autologous chondrocyte implementation are now giving way to single arthroscopic stage techniques.Tissue engineering techniques, including stem cells and biomimetic tissues, will become the basis for the next generation of cartilage regeneration.

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Podium Presentation Joint Specific Cartilage Repair

19.3.6 - A Comprehensive Functional Evaluation System Of The Regenerative Cartilage (ID 9393)

Presentation Number
19.3.6
Topic
Joint Specific Cartilage Repair
Lecture Time
11:53 - 12:02
Corresponding Author
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

One of the essential requirements that helps to maintain the normal joint motor function is the incomparable tribological property of the articular cartilage. Hidden clinical risks will be inevitably left over in the use of regenerative cartilage repairs with poor wear resistance.

Methods and Materials

Here we compared two different strategies, bone marrow enrichment plus microfracture and Bio-Gide® matrix cartilage repairing system (BME-MB),and microfracture plus Bio-Gide® matrix technique (MB), in the sheep cartilage defect repair.

Results

We identified that superior to the MB group, the wear resistant performance of the BME-MB regenerative cartilage was more close to the native cartilage, whether in the changing of the surface friction coefficient, surface roughness, volume loss, weight loss, the quantity and stiffness of the wear particles, as well as the expression and continuity of the cartilage "protective protein", proteoglycan 4 (PRG4).

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Conclusion

This leads to the establishment of a novel wear resistance-centered evaluation system, which helps to assess the cartilage durability, avoid the clinical risk, reduce the dispensable time and money cost in the translational medicine of cartilage regeneration.

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Podium Presentation Cartilage /Cell Transplantation

13.3.2 - A Single Stage Arthroscopic Autologous Collagen Induced Chondrogenesis - Five Year Results (ID 9394)

Presentation Number
13.3.2
Topic
Cartilage /Cell Transplantation
Lecture Time
13:39 - 13:48
Corresponding Author
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

Chondral injuries of the knee are common and often seen in young and active individuals. We describe a single stage arthroscopic procedure for the treatment of articular cartilage defects in the knee. It involves micro drilling (MD) and application of Atelo-Collagen with fibrin gel. The study aimed to evaluate the clinical and radiological outcomes at five years.

Methods and Materials

The pre-clinical study involved two groups of rabbits, treated with Microdrilling (MD) alone and MD and Atelocollagen combined with fibrin gel application. New cartilage from both groups was subjected to staining with hematoxylin-eosin for tissue morphology, toluidine blue for collagen and safranin O for GAG content; immunohistochemistry with antibodies IH11 and CIIC1 for collagen type I and II respectively; and scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to analyze the microstructural morphologies. The fibrin gel-Atelocollagen group scored better than the MD group, on all counts.

This prospective study of 30 patients with symptomatic ICRS grade III/IV chondral defects, ranging from 2-8cm2. The surgical procedure involved debridement of the lesion, MD, and application of Atelo-Collagen with fibrin gel under CO2 insufflation. Patients underwent morphological MRI, quantitative T2*-mapping, and d-GEMRIC scan. Clinical assessment employed the Lysholm, IKDC and KOOS scores while the radiological assessment was performed with MOCART score.

Results

At five-year, Lysholm score was 78, compared to 50.8 pre-operatively (p < 0.05). KOOS (symptomatic) was 90, compared to 65.7 pre-operatively. IKDC (subjective) was 80 from 39 preoperatively. The mean T2* relaxation-times for the repair tissue and native cartilage were 26 and 29.9 respectively. Average MOCART score for all lesions was 70.

Conclusion

This technique shows encouraging clinical results at five-year follow-up. The morphological MRI shows good cartilage defect filling, and the biochemical MRI (T2*-mapping) suggests hyaline-like repair tissue.

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Poster Stem Cells

P268 - Antimir-221 Loaded Fibrin/Hyaluronic Acid Hydrogel For The Guidance Of Endogenous Cartilage Repair (ID 9396)

Presentation Number
P268
Topic
Stem Cells
Lecture Time
10:45 - 10:45
Session Name
11.0 - Poster Viewing / Exhibition (ID 780)
Corresponding Author
Disclosure
A. Yayon, ProCore Bio Med Ltd., CEO ProCore Bio Med Ltd. owns the patent and commercializes the fibrin/hyaluronic acid hydrogel (RegenoGel™) used in this work.

Abstract

Purpose

Strategies promoting endogenous cartilage repair aim to recruit endogenous mesenchymal stem cells (MSCs) to injuries, subsequently inducing in situ chondrogenesis. Previously, we showed that silencing microRNA(miR)-221 in hMSCs in vitro strongly enhanced their cartilage production in vivo. We here focused on the establishment of a fibrin/hyaluronic acid (FB/HA) hydrogel delivery system to inhibit miR-221 in situ, for guiding endogenous cartilage repair.

Methods and Materials

In vitro invasion of FB/HA by CFDA-SE-labelled bone marrow hMSCs was assessed by confocal imaging. Chondrogenesis was confirmed by qRT-PCR and histology. An animal cartilage defect model (bovine osteochondral plugs implanted subcutaneously in athymic mice) was employed to assess endogenous cell invasion and cartilage production in vivo. FB/HA was loaded with fluorescent LNA-antimiR-221 (25÷250nM). The release profile was monitored over 7 days and FB/HA mediated silencing in hMSCs was determined by qRT-PCR.

Results

When cultured onto FB/HA, hMSCs infiltrated the hydrogel within 7 days. FB/HA supported in vitro hMSCs chondrogenesis, as shown by collagen II and aggrecan expression and glycosaminoglycan production (Fig. 1A). In vivo, FB/HA demonstrated abundant endogenous cell invasion after 4 weeks, but limited and variable cartilage production was observed, suggesting that further cues are needed to promote chondrogenesis (Fig. 1B). Thus, we functionalized FB/HA with antimiR-221/lipofectamine complexes. FB/HA strongly retained antimiR-221 over time, with minimal release of the molecule over 14 days of culture (12,7%). Culture of hMSCs in antimiR-221 loaded FB/HA led to complete knockdown of miR-221 within 7 days (≥ 95% silencing for antimiR ≥ 100nM) (Fig. 2).

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fig.2 icrs abstract.jpg

Conclusion

FB/HA allowed abundant cell infiltration in vitro and in vivo, but on its own led to limited and variable cartilage production. By functionalizing FB/HA with antimiR-221, we developed a novel construct that mediates knockdown of the anti-chondrogenic miR-221 in invading hMSCs in situ. Our delivery system may be employed for enhancing cartilage repair by endogenous stem cells.

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Poster Osteochondral Grafts

P224 - Contralateral Lateral Femoral Condyle Allografts Provide Acceptable Match for OCD Lesions Of The Medial Femoral Condyle (ID 9397)

Presentation Number
P224
Topic
Osteochondral Grafts
Lecture Time
10:45 - 10:45
Session Name
11.0 - Poster Viewing / Exhibition (ID 780)
Disclosure
J. Grant, JRF Ortho, Grant Research Support; J. Grant, Ossur Inc., Consultant

Abstract

Purpose

The purpose of this study was to determine whether contralateral lateral femoral condyle (LFC) allografts can provide an acceptable (<1mm deviation) surface topography match for classic osteochondritis dessicans (OCD) lesions of the medial femoral condyle (MFC).

Methods and Materials

A 20mm circular osteochondral “defect” with the anterior edge 1cm posterior and 1cm medial to the roof of the intercondylar notch was created in the recipient MFC (n=10). A randomly ordered donor MFC or LFC plug was harvested, transplanted (Fig 1A), scanned with nano-CT, reconstructed (Fig 1B), registered to an initial scan of the recipient MFC, and processed in MATLAB to determine the height deviation (dRMS) between the native and donor surfaces (Fig 1C), percent area unacceptably proud (>1mm; %Aproud) and sunken (<-1 mm; %Asunk). Step-off height (hRMS), percent circumference unacceptably proud (>1mm; %Cproud) and sunken (< -1mm; %Csunk) were measured using DragonFly software (Fig 1D). The process was then repeated for the other allograft plug. Two-way mixed ANOVAs with Sidak corrections for multiple comparisons (a=0.05) were used.

figure1.jpg

Results

Both MFC and LFC plugs showed acceptable step-off heights in all four quadrants. LFC plugs did not significantly differ from MFC plugs with respect to all measured parameters (dRMS, %Aproud, %Asunk, hRMS, %Cproud, and %Csunk) (Table 1). In general, plugs were more unacceptably sunken than proud circumferentially. Within LFC plugs, %Cproud was significantly greater laterally compared to all other locations around the plug (p<0.0001).

table 1.jpg

Conclusion

Similar to centrally located defects, allograft type was found to not have an effect on surface deviation or step-off height for medial OCD lesions. With comparable dRMS, %Aproud, %Asunk, hRMS, %Cproud, and %Csunk, both MFC and LFC allografts can be expected to present similar stresses on the knee joint and achieve predictably positive clinical outcomes, thus improving donor availability and reducing surgical wait times for matches.

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Podium Presentation Stem Cells

19.4.8 - hWJMSCs Co-cultured with pACs in ACECM Oriented Scaffold Improve Cartilage Repair in a Caprine Model (ID 9398)

Presentation Number
19.4.8
Topic
Stem Cells
Lecture Time
12:18 - 12:27
Corresponding Author
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

To explore the effectiveness of tissue engineering cartilage constructed by a novel method using human Umbilical Cord Wharton’s Jelly mesenchymal stem cells(hWJMSCs) co-cultured with primary articular cartilage cells(pACs) in accellular cartilage extracellular matrix(ACECM) oriented scaffold to repair full-thickness cartilage defect in a caprine model.

Methods and Materials

The tissue engineering cartilage constructed by hWJMSCs co-culturing with pACs in different ratios in ACECM oriented scaffold. After co-culturing for 1 week and 3 weeks, all samples were tested the levels of genes and proteins, cellular biobehavior and the optimal ratio group was transplanted to repair full-thickness cartilage defect in caprine model. After 6 and 9 months, the effectiveness of co-culture group was evaluated in macroscopy, histology, biomechanics and imaging test compared with blank control group and monoculture groups.

Results

In vitro, hWJMSCs undergone chondrogenic differentiation in native-like chondrocytes microenvironment consisting of pACs and ACECM oriented scaffold due to the upregulation of gene collagenand aggrecan, while the cytoactive of pACs was significant improved compared with monocuture. The optical ratio co-culture group was successfully achieved a full cartilage- like tissue regeneration in 6 months. Compared with blank control group, the histological score and biomechanics of co-culture group were significant higher in 6 months and 9 months. The magnetic resonance imaging showed the neo-tissue of co-culture group was uniform and no obvious marrow edema signal, which weren’t found in monoculture groups.

Conclusion

Co-culture system consisted of hWJMSCs, pACs and ACECM oriented scaffold was benefit to the chondrogenic differentiation of hWJMSCs and cytoactive promotion of pACs, which made enormous contributions to the repair and regeneration of articular cartilage in caprine model. This novel method is a promising strategy to overcome predicaments of seed cells in articular cartilage tissue engineering including unstable chondrogenic differentiation of stem cells and deficiency of chondrocytes in the future.

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Podium Presentation Osteoarthritis

19.2.6 - Lipoxin A4 Plays A Key Role In Therapeutic Effects Of Treadmill Exercise On Osteoarthritis In Rats (ID 9399)

Presentation Number
19.2.6
Topic
Osteoarthritis
Lecture Time
11:51 - 12:00
Corresponding Author
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

The aim was to evaluate the role of lipoxin A4 (LXA4) in therapeutic effects of different intensity treadmill exercise on rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA).

Methods and Materials

One hundred and twenty-four male Sprague-Dawley rats were submitted to two different treadmill exercise protocols: a single session of treadmill exercise or formal treadmill exercise. A single session of treadmill exercise: sixty-four rats were randomly divided into different intensity treadmill exercise for 60 min only once. Serum and intra-articular lavage fluid (IALF) were collected at different time after treadmill exercise (n=4). Formal treadmill exercise: sixty rats were randomly divided into six groups (n=10): control group (CG), knee OA group (OAG), OA with low, moderate and high intensity treadmill exercise (OAL, OAM and OAH), and OAM + BOC-2 (an antagonist of LXA4 receptor). Exercise was 60 min/day, 5 days/week for 4 weeks. The rats were evaluated by ELISA, histology, immunohistochemistry and western blotting. Fibroblast-like synoviocytes (FLSs) were obtained from knee joint of rats. The effects of LXA4 on interleukin (IL)-1β induced FLSs were evaluated by western blotting and immunofluorescence.

Results

The results of ELISA, histological evaluation, western blotting and immunohistochemistry indicated that the OAM had a better treatment which could be suppressed by BOC-2. Moreover, LXA4 could attenuate the expression of matrix metalloproteinase (MMP)-3 and MMP-13 and suppress the nuclear translocation of NF-κB p65 induced by IL-1β in FLSs.

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Conclusion

Conclusion: LXA4 play a key role in therapeutic effects of treadmill exercise on MIA-induced OA which is modulated by NF-κB signaling pathway.

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Podium Presentation Osteoarthritis

26.4.5 - Diabetes Mellitus Accelerates Progression of Osteoarthritis in Streptozotocin-induced Diabetic Mice (ID 9400)

Presentation Number
26.4.5
Topic
Osteoarthritis
Lecture Time
11:06 - 11:15
Corresponding Author
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

Diabetes mellitus (DM) has been demonstrated to be an independent risk factor of osteoarthritis (OA). 1) to develop a DM-OA model; 2) to validate diabetes aggravates OA; 3) to evaluate the microarchitecture, chemical composition and biomechanical properties of subchondral bone (SB) as a consequence of the damaged induced by diabetes OA.

Methods and Materials

Mice were divided into DM-OA, OA, Sham group. DM-OA group was injected streptozotocin to induce diabetes. OA was surgically induced in DM-OA and OA groups by transected ACL. Animals were sacrificed at 4, 8, 12 weeks after operation. Joints were decalcified for histological analysis. Undecalcifed joints were used to evaluate properties of SB using confocal Raman microspectroscopy to measure chemical composition, and microindentation to measure biomechanical properties. Micro‑CT imaging was to evaluate structure, with subsequent mechanical compression of the SB to investigate fracture properties.

Results

OARSI score of DM-OA group was higher than other groups at 8, 12 weeks. The number of osteoclasts in DM-OA group was higher than other groups at 8, 12 weeks. Conversely, mineral-to-collagen ratio, microindentation elastic modulus and hardness of DM-OA group was lower than other two groups at 8, 12 weeks. Micro-architectural parameters showed bone volume fraction, trabecular thickness and bone mineral density of DM-OA group to be lower than other groups at 12 weeks. Trabecular spacing and structural model index was higher compared to other groups at 12 weeks. Fracture properties, including stiffness and fracture load, of DM-OA group were also reduced at 12 weeks.figure 1.giffigure 2.gif

Conclusion

Pathology results from DM-OA group were worse, proving diabetes to aggravate OA pathogenesis. Diabetes elevated the number of osteoclasts and deteriorated the structure of SB. Trabecular biomechanical properties were declined due to a decrease in bone mineral density in the DM-OA group. The weakened biomechanical properties of SB make it more vulnerable to failure.

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Poster Clinical Outcome

P123 - Changes of Patellofemoral Arthritis After Medial Open Wedge High Tibial Osteotomy (ID 9403)

Presentation Number
P123
Topic
Clinical Outcome
Lecture Time
10:45 - 10:45
Session Name
11.0 - Poster Viewing / Exhibition (ID 780)
Corresponding Author
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

Previous studies have suggested negative effects of open wedge high tibial osteotomy (OWHTO) on patellofemoral (PF) joints. However, the details have not yet been fully clarified. The purpose of this study was to evaluate the changes of articular cartilage of PF joints before and after OWHTO.

Methods and Materials

The study involved 41 knees in 37 patients (22 males, 15 females, average 57.0 years old) who underwent OWHTO for the treatments of medial-compartment osteoarthritis and also received a second-look arthroscopy at the time of plate removal ( average of 13.1 months after OWHTO). The status of cartilage degeneration and injury in the PF joint was evaluated arthroscopically using the International Cartilage Repair Society (ICRS) grading system at the time of OWHTO and second-look arthroscopy. Clinical evaluations were performed using the Knee Society Score (KSS). The ROC curve analysis was performed to examine the relationships between the amount of the medial opening gap during and the progression of the ICRS grade in the PF joints.

Results

KSS was significantly improved after surgery (P< 0.01). The ICRS grade for patella and trochlea progressed in 9 knees (22.0%) and 12 knees (29.3%) respectively. The mean medial opening gap was 12.6 mm (8 -19mm). The ROC curve analysis showed that the cut-off value for progression of the ICRS grading was 15 mm in both patellar side and trochlear side. The ratio of the patients who had a progressed ICRS grading was significantly higher in the patients who had a medial opening gap of >=15mm compared with the patients who had a medial opening gap of < 15mm.

Conclusion

There was a tendency that cartilage damages in the PF joints progress after OWHTO in patients who had a medial opening gap of >=15 mm and a caution may be necessary when performing OWHTO.

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Poster Biomaterials and Scaffolds

P55 - Pain Relief In A Synovitis Model By Intra-Articular Injection Of Triamcinolone Acetonide Biomaterial Microspheres (ID 9404)

Presentation Number
P55
Topic
Biomaterials and Scaffolds
Lecture Time
10:45 - 10:45
Session Name
11.0 - Poster Viewing / Exhibition (ID 780)
Corresponding Author
Disclosure
No Significant Commercial Relationships

Abstract

Purpose

Inflammation in an osteoarthritic joint predominantly causes pain and stimulates cartilage matrix breakdown. Triamcinolone acetonide (TAA) is intra-articularly injected to alleviate pain and reduce inflammation temporarily. Since multiple injections entail risks, local sustaining TAA release can overcome such disadvantages. PLGA formulations of TAA has been shown to effectively prolong inhibited pain in OA, but is limited to 4 weeks. A novel polyesteramide (PEA) microsphere platform based on natural α-amino acids previously showed release in the joint for over 3 months. To evaluate its capacity for sustained TAA release in inhibiting pain and inflammation, PEA microspheres loaded with TAA were locally delivered in a rat model of acute inflammatory arthritis.

Methods and Materials

Localized synovitis was induced in the left knee of 18 adult Sprague-Dawley rats by intra-articular injection of streptococcal-cell-wall-peptidoglycan-polysaccharide (PGPS with 5 mg rhamnose/mL) (priming, day -14). Synovitis flare-ups were evoked every 2 weeks by administration of intravenous PGPS. 2.5 hours prior first reactivation (day 0), 25 µl unloaded and loaded microspheres with 2.5 mg/ml TAA or bolus TAA (2.5 mg/ml) were intra-articularly delivered in the affected knee. Differences in joint thickness, dynamic weight-bearing, paw withdrawal latency and lameness was scored to compare the effect of prolonged sustained TAA release.

Results

Joint thickness was significant increased due to synovitis flare-ups and bolus TAA injection could not reduce this swelling over the entire study period, whereas a single injection of controlled released TAA was able to reduce this. Furthermore, sustained release of TAA restored paw withdrawal latencies, improved weight symmetry, paw surface placement and lameness of affected limb. Post-termination microCT images and corresponding histopathology are currently being analyzed.

Conclusion

Sustained suppression of synovitis by controlled TAA release from the PEA platform provides prolonged reduction of joint inflammation, functional improvement and pain relief over an extended period after single injection.

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