S. Tabbaa (Flagstaff, US)

University of California, San Franciso

Presenter Of 3 Presentations

Podium Presentation Allografts

16.3.4 - An Analysis of Factors that Influence Meniscal Allograft Size Discrepancies Between Patient and Donor Populations

Presentation Topic
Allografts
Date
14.04.2022
Lecture Time
11:51 - 12:00
Room
Potsdam 1
Session Name
Session Type
Free Papers
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Successful outcomes of meniscal allograft transplantation are dependent on adequate size matching of donor and patient meniscus. The extent that donor pools meet the demands of the patient pool is unknown. The purpose of this study was to analyze the variability in meniscus size and anthropometric data between donors (supply) and patients (demand), and determine the impact on time to match.

Methods and Materials

Lateral and medial meniscal measurements, sex, patient height and weight, and time to match a donor graft were extracted from a tissue supplier database. Distributions of meniscus size for patient and donor pools were analyzed. Body Mass Index (BMI), meniscus area, body mass to meniscus area index (BMMI), and height to meniscus area index (HMI) were compared via chi-square tests and independent samples t-test. The effect of size on time to match was analyzed using ANOVA and post-hoc Tukey test.

Results

The distributions of meniscus sizes were significantly different for meniscus donor and patient populations (Fig1A-D). The lateral meniscus patients showed a higher frequency of larger size meniscus and the medial meniscus patients showed a higher frequency of smaller size meniscus. The lateral meniscus analysis showed significantly greater meniscus area and increased average height in the patient population. The medial meniscus analysis showed significantly smaller meniscus areas in the patient population contributing to an increased BMMI and HMI. The time to match a donor meniscus was affected by the patient meniscus size.

dia1.jpgFigure 1: Distribution of donor (blue) and patient (gray) meniscus sizes.

Conclusion

This analysis demonstrates variations in frequency of meniscus sizes between donor and patient populations. This variation is attributed to significant differences in anthropometric data between patient and donor populations. This work identifies a mismatch between demand and supply. Areas of size mismatch were further substantiated by the longer time period to identify a donor match.

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Poster Osteochondral Grafts

P174 - Fresh Osteochondral and Chondral Allograft Preservation and Storage Media: A Systematic Review of the Literature

Presentation Topic
Osteochondral Grafts
Date
13.04.2022
Lecture Time
09:30 - 09:30
Room
Exhibition Foyer
Session Name
7.3 - Poster Viewing / Coffee Break / Exhibition
Session Type
Poster Session
Disclosure
S. Tabbaa, JRF Ortho, Consultant, Restoration Biologics LLC, Member; F. Guilak, Restoration Biologics LLC, Member, Cytex Therapeutics, Employee and Shareholder; Bugbee, JRF Ortho, Consultant, Restoration Biologics LLC, Member

Abstract

Purpose

Storage procedures and parameters have a significant influence on the health of fresh osteochondral allograft (OCA) cartilage. To date, there is lack of agreement on the optimal storage conditions for OCAs. The purpose of this study was to systematically review the literature on (i) experimental designs and reporting of key variables of ex vivo (laboratory) studies (ii) the effects of various storage solutions and conditions on cartilage health ex vivo, and (iii) in vivo animal studies and human clinical studies evaluating the effect of fresh OCA storage on osteochondral repair and outcomes.

Methods and Materials

A systematic review was performed using PubMed, EMBASE, and Cochrane databases. The inclusion criteria included laboratory studies (ex vivo) reporting cartilage health outcomes following prolonged storage (> 3 days) of fresh osteochondral or chondral tissue explants, and animal studies (in vivo) reporting outcomes of fresh OCA. Frozen, cryopreserved, decellularized, synthetic, or tissue-engineered grafts were excluded.

Results

Fifty-five peer-reviewed articles met the inclusion criteria. Ex vivo studies reported a spectrum of tissue sources and storage solutions and conditions, although the majority of studies lacked complete reporting of key variables including storage solution formula and environmental conditions (Fig. 1). The effect of various conditions and storage solutions, such as temperature, on cartilage health were inconsistent. Although 60% of animal models suggest storage time may influence outcomes and 80% suggest inferior outcomes with frozen OCA compared to fresh OCA, 75% of clinical studies report no correlation between storage time and outcomes (Fig. 2).

icrs 2021 systematic review figure 1.jpg

icrs 2021 systematic review figure 2.jpg

Conclusion

Due to the variability in experimental designs and lack of reporting across studies, it is still not possible to determine optimal storage conditions, although animal studies suggest storage time and chondrocyte viability influence osteochondral repair outcomes. High quality clinical data is needed to investigate the effects of storage and graft health on outcomes.

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Poster Osteochondral Grafts

P175 - Understanding the Mechanism of Cartilage Health Decline during Osteochondral Allograft Storage: Metabolomic Analysis of Storage Media

Presentation Topic
Osteochondral Grafts
Date
13.04.2022
Lecture Time
09:30 - 09:30
Room
Exhibition Foyer
Session Name
7.3 - Poster Viewing / Coffee Break / Exhibition
Session Type
Poster Session
Disclosure
S. Tabbaa, JRF Ortho, Consultant, Restoration Biologics LLC, Member F. Guilak, Restoration Biologics LLC, Member, Cytex Therapeutics, Employee and Shareholder L. Lemmerman, Restoration Biologics LLC, Consultant W. Bugbee, JRF Ortho, Consultant, Restoratio

Abstract

Purpose

A major limitation of osteochondral allografts (OCA) is deterioration of cartilage health during prolonged storage. Despite limited understanding of the mechanism associated with chondrocyte death during storage, it is well established that chondrocyte viability in OCA is a critical factor for repair and clinical outcomes. The purpose of this study was to determine if bioactive metabolites impact chondrocyte death and graft health during storage.

Methods and Materials

To elucidate potential mechanisms of cartilage health decline during storage, fresh human hemi-condyle osteochondral allograft tissues and media provided by a US tissue bank were analyzed at Day 7, Day 28, and Day 68 of prolonged cold storage. Targeted metabolomics analysis measured bioactive fatty acids using mass spectrometry. Primary (ROOH) and secondary (MDA) lipid oxidation were measured. Chondrocyte viability and viable cell density was measured using standard LIVE/DEAD and confocal microscopy. One- and two-way ANOVAs with post-hoc Tukey tests were used to compare differences in early and later time points of prolonged cold storage.

Results

All fatty acid metabolites (Figure 1) significantly increased with increased storage time except for stearic acid (p<0.05). LOOH was significantly higher at Day 28 of storage. No difference in secondary lipid peroxide product were observed. Consistent with previous reports, LIVE/DEAD (Figure 2) showed significant decline in chondrocyte viability in both the en face and vertical cross-section analysis with increased storage time (p<0.05).

icrs oca metabolomics figure 1 final.png

icrs 2021 oca metabolomics fig 2.png

Conclusion

It is well established that elevated levels of certain fatty acids and lipid oxidation can alter cell function and cause cell death through lipotoxicity and other mechanisms. This work identified levels of fatty acids and oxidation in the storage media which have both been shown to affect cell dysfunction and death in other non-adipose tissues. These findings provide important targets for understanding why cartilage health declines during storage to better optimize media formulations and improve graft health.

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Presenter Of 2 Presentations

Osteochondral Grafts

P174 - Fresh Osteochondral and Chondral Allograft Preservation and Storage Media: A Systematic Review of the Literature

Abstract

Purpose

Storage procedures and parameters have a significant influence on the health of fresh osteochondral allograft (OCA) cartilage. To date, there is lack of agreement on the optimal storage conditions for OCAs. The purpose of this study was to systematically review the literature on (i) experimental designs and reporting of key variables of ex vivo (laboratory) studies (ii) the effects of various storage solutions and conditions on cartilage health ex vivo, and (iii) in vivo animal studies and human clinical studies evaluating the effect of fresh OCA storage on osteochondral repair and outcomes.

Methods and Materials

A systematic review was performed using PubMed, EMBASE, and Cochrane databases. The inclusion criteria included laboratory studies (ex vivo) reporting cartilage health outcomes following prolonged storage (> 3 days) of fresh osteochondral or chondral tissue explants, and animal studies (in vivo) reporting outcomes of fresh OCA. Frozen, cryopreserved, decellularized, synthetic, or tissue-engineered grafts were excluded.

Results

Fifty-five peer-reviewed articles met the inclusion criteria. Ex vivo studies reported a spectrum of tissue sources and storage solutions and conditions, although the majority of studies lacked complete reporting of key variables including storage solution formula and environmental conditions (Fig. 1). The effect of various conditions and storage solutions, such as temperature, on cartilage health were inconsistent. Although 60% of animal models suggest storage time may influence outcomes and 80% suggest inferior outcomes with frozen OCA compared to fresh OCA, 75% of clinical studies report no correlation between storage time and outcomes (Fig. 2).

icrs 2021 systematic review figure 1.jpg

icrs 2021 systematic review figure 2.jpg

Conclusion

Due to the variability in experimental designs and lack of reporting across studies, it is still not possible to determine optimal storage conditions, although animal studies suggest storage time and chondrocyte viability influence osteochondral repair outcomes. High quality clinical data is needed to investigate the effects of storage and graft health on outcomes.

Collapse
Osteochondral Grafts

P175 - Understanding the Mechanism of Cartilage Health Decline during Osteochondral Allograft Storage: Metabolomic Analysis of Storage Media

Abstract

Purpose

A major limitation of osteochondral allografts (OCA) is deterioration of cartilage health during prolonged storage. Despite limited understanding of the mechanism associated with chondrocyte death during storage, it is well established that chondrocyte viability in OCA is a critical factor for repair and clinical outcomes. The purpose of this study was to determine if bioactive metabolites impact chondrocyte death and graft health during storage.

Methods and Materials

To elucidate potential mechanisms of cartilage health decline during storage, fresh human hemi-condyle osteochondral allograft tissues and media provided by a US tissue bank were analyzed at Day 7, Day 28, and Day 68 of prolonged cold storage. Targeted metabolomics analysis measured bioactive fatty acids using mass spectrometry. Primary (ROOH) and secondary (MDA) lipid oxidation were measured. Chondrocyte viability and viable cell density was measured using standard LIVE/DEAD and confocal microscopy. One- and two-way ANOVAs with post-hoc Tukey tests were used to compare differences in early and later time points of prolonged cold storage.

Results

All fatty acid metabolites (Figure 1) significantly increased with increased storage time except for stearic acid (p<0.05). LOOH was significantly higher at Day 28 of storage. No difference in secondary lipid peroxide product were observed. Consistent with previous reports, LIVE/DEAD (Figure 2) showed significant decline in chondrocyte viability in both the en face and vertical cross-section analysis with increased storage time (p<0.05).

icrs oca metabolomics figure 1 final.png

icrs 2021 oca metabolomics fig 2.png

Conclusion

It is well established that elevated levels of certain fatty acids and lipid oxidation can alter cell function and cause cell death through lipotoxicity and other mechanisms. This work identified levels of fatty acids and oxidation in the storage media which have both been shown to affect cell dysfunction and death in other non-adipose tissues. These findings provide important targets for understanding why cartilage health declines during storage to better optimize media formulations and improve graft health.

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