Importance of Donor Chondrocyte Viability for Osteochondral Allografts

Stannard, James P.; Cook, James L.; Stoker, Aaron M.; Bozynski, Chantelle C.; Kuroki, Keiichi; Cook, Cristi R.; Pfeiffer, Ferris M.

doi:10.1177/0363546516629434

Cited by 101 publications

(145 citation statements)

References 41 publications

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“…In order to validate these in vitro study findings, Cook et al (2014Cook et al ( , 2016 conducted a preclinical canine model study. In this study, canine femoral condyle OCAs were stored for 28 or 60 days after procurement at room temperature using our novel protocol with a proprietary media named Media 3 and a proprietary container named "C" compared to the SOC tissue bank protocol at 4 C. Mean chondrocyte viability in OCAs stored in our protocol was 82% at day 28 and 89% at day 60 while for those stored using the SOC protocol was 60% at day 28 and 52% at day 60.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, all OCAs were negative for microbial growth at all time points when tested according to the current U.S. Pharmacopeia <71> protocol (www.pharmawe binars.com/usp-71-pharma-webinars/), and extracellular matrix composition and biomechanical properties were Media 3 (every 7 days) C >100% at day 63 Figure 1. Radiographic and histologic comparison between an unsuccessful osteochondral allograft (OCA) preserved 60 days with a current standard of care protocol and a successful OCA preserved 60 days in our novel protocol (MOPS™) 6 months after press-fit implantation in femoral condyles from a preclinical canine model study (Cook et al, 2016;Cook et al, 2014). Radiographically, an unsuccessful OCA in medial femoral condyle shows mild articular surface irregularities (box) while a successful OCA in medial femoral condyle shows smooth articular surface (box).…”

Section: Resultsmentioning

confidence: 99%

“…For all experiments, chondrocyte viability was determined using Calcein AM (Invitrogen, Carlsbad, CA) for the live cell stain and either ethidium homodimer-1 (Invitrogen, Carlsbad, CA) or SYTOX Blue (Invitrogen, Carlsbad, CA) for visualizing dead cells as described elsewhere (Cook et al 2014(Cook et al , 2016Garrity et al 2012;). In addition, histologic integrity of OCAs was evaluated using the Osteoarthritis Research Society International (OARSI) system ).…”

Section: Methodsmentioning

confidence: 99%

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Biologic Joint Repair Strategies: The Mizzou BioJoint Story

et al. 2017

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Because articular cartilage has very limited healing potential, most symptomatic cartilage injuries eventually result in end-stage osteoarthritis and are treated with artificial joint replacement. Our interdisciplinary, comparative orthopedic research performed by a team of DVMs, MDs, engineers, and basic scientists has yielded marked progress toward effective biologic joint restoration strategies by bringing bench-side ideas to fruition in bedside applications in both canine and human patients. This mini-review summarizes the progress of biologic joint restoration strategies at our center.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Biologic Joint Repair Strategies: The Mizzou BioJoint Story

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“…Currently, many different biomaterials are under experimental investigation or are already used in clinical applications (Cook et al 2016). These biomaterials are composed of natural polymers like collagen (Gille et al 2010; Pascarella et al 2010), agarose (Wang et al 2011), hyaluronan (Solchaga et al 2000; Kang et al 2009), synthetic polymers (e.g.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronan thiomer gel/matrix mediated healing of articular cartilage defects in New Zealand White rabbits—a pilot study

et al. 2017

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BackgroundArticular cartilage defects are limited to their regenerative potential in human adults. Our current study evaluates tissue regeneration in a surgically induced empty defect site with hyaluronan thiomer as a provisional scaffold in a gel/matrix combination without cells on rabbit models to restore tissue formation.MethodsAn osteochondral defect of 4 mm in diameter and 5 mm in depth was induced by mechanical drilling in the femoral center of the trochlea in 18 New Zealand White rabbits. Previously evaluated from an in vitro study hyaluronan thiomer matrix, and a hyaluronan thiomer gel was used to treat the defect. As a control, the defect was left untreated. During the whole study, rabbits were clinically examined and after 4 (n = 3) or 12 (n = 3) weeks, the rabbits were sacrificed. Joints were evaluated macroscopically (Brittberg score) and by histology (O’Driscoll score). Synovial cells from the synovial fluid smear were histopathologically evaluated.ResultsThe healing of the defects varied intra-group wise at the first observation period. After 12 weeks the results concerning the cartilage repair score were inhomogeneous within each group, while the macroscopic analysis was more homogenous. In the synovial fluid smear, the mean score of infiltrated synovial and non-synovial cells was slightly increased after 4 weeks and slightly decreased after 12 weeks in both the treatment groups in comparison to the untreated control.ConclusionsTaken together with results from the in vivo study indicated that implantation of hyaluronan thiomer as a combination of gel and matrix might enhance articular cartilage regeneration in an empty defect. Despite their benefits, the intrinsic healing capacity of New Zealand rabbits is a limitation for comparative test subject in pre-clinical models of cartilage defects.

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“…One of the major causes of failure for OCA transplantation is loss of essential chondrocyte viability during the preservation and storage period of tissue prior to eligible patient matching and transplantation. Essential chondrocyte viability for OCAs is considered to be at least 70% of day 0 viable chondrocyte density with successful preclinical and clinical outcomes strongly corresponding to this key metric for graft quality . While chondrocyte viability at time of OCA transplantation has been reported to be a contributing factor to successful outcomes, it is also possible that metabolic responses of the OCA in transitioning from storage temperature to body temperature may contribute to mechanisms causing failure.…”

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Metabolic responses of osteochondral allografts to re‐warming

Stoker

Caldwell

Stannard

et al. 2019

Journal Orthopaedic Research

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Symptomatic chondral and osteochondral defects affect a large and growing number of patients. A safe and effective surgical treatment for large articular defects is osteochondral allograft (OCA) transplantation. One of the major causes of failure for OCA transplantation is loss of essential chondrocyte viability during the preservation and storage period. It is also possible that metabolic responses of the OCA when transitioning from storage temperature to body temperature may contribute to mechanisms causing failure. The present study was designed to compare MOPS SM -preserved OCAs to those stored using the current standard of care (SOC) method with respect to metabolic responses when rewarmed for transplantation to and maintenance at body temperature (37˚C). It was theorized that grafts stored using the MOPS SM protocol would maintain significantly higher chondrocyte viability and produce significantly lower levels of inflammatory mediators and degradative enzymes, and significantly higher levels of chemokines compared to grafts stored using the SOC protocol. Left over SOC and MOPS SM -stored OCA tissues were collected after surgery, and cartilage explants were cultured for 6 days. Media was analyzed for biomarkers using commercially available assays. Cartilage from SOC grafts released significantly higher levels of PGE2, MMP-1, MMP-2, and MMP-13, and significantly lower levels of IL-8 and Groa, compared to cartilage from MOPS SM -stored grafts. Clinical significance: These data suggest that OCAs stored using the MOPS SM protocol have potentially less detrimental initial inflammatory and degradative responses to re-warming for transplantation compared to OCAs stored using the current tissue bank protocols. ß

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Importance of Donor Chondrocyte Viability for Osteochondral Allografts

Abstract: Optimizing chondrocyte viability in all aspects of OCA transplantation-including procurement, processing, storage, transportation, and surgical implantation-needs to be a primary focus for OCA clinical use.

Cited by 101 publications

References 41 publications

Biologic Joint Repair Strategies: The Mizzou BioJoint Story

Biologic Joint Repair Strategies: The Mizzou BioJoint Story

Hyaluronan thiomer gel/matrix mediated healing of articular cartilage defects in New Zealand White rabbits—a pilot study

Metabolic responses of osteochondral allografts to re‐warming

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