PRP-fibrinogen gel-like chondrocyte carrier stabilized by TXA-preliminary study

Sitek, Patrycja; Wysocka-Wycisk, Aleksandra; Kępski, Fabian; Król, Dorota; Bursig, Henryk; Dyląg, Stanisław

doi:10.1007/s10561-011-9290-0

Cited by 19 publications

(17 citation statements)

References 16 publications

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“…Observed cytotoxicity is most likely a product of concentration and exposure time. Studies on the effect of topical TXA on chondrocytes and cartilage tissue suggest a threshold for toxicity of around 25 mg/ml with at least 3 h of exposure, and cells embedded in a natural (cartilage) or artificial (hydrogel) matrix are more resilient 13,20,24 . Furst and colleagues 25 reported 50 per cent viability in human fibroblasts exposed to TXA 100 mg/ml and 65 per cent viability for 50 mg/ml after 100 min of exposure; this is an intermediate exposure time compared with the present 10 min for limited exposure and 24-72 h for chronic exposure.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity and effect on wound re‐epithelialization after topical administration of tranexamic acid

et al. 2019

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BackgroundTopical administration of tranexamic acid (TXA) reduces bleeding from surgical wounds similarly to intravenous use, but with negligible risk of adverse systemic events. Topical use is expanding, but is off‐label. Surgeons lack guidelines regarding safe topical dosages and modes of administration. The effects of topical TXA on skin cells and wound healing are unknown. This study investigated whether topical TXA might be cytotoxic or affect wound re‐epithelialization.MethodsHuman keratinocytes and fibroblast cell cultures and an ex vivo human skin wound model were subjected to both short (limited) and long (chronic) exposure to various clinically relevant concentrations of TXA to mimic different modalities of topical administration. Cytotoxicity and effects on wound re‐epithelialization were evaluated.ResultsIn cell culture, toxicity from chronic exposure was associated with increasing concentration and exposure time. Limited exposure to TXA did not cause significant cytotoxicity even at high concentrations. Re‐epithelialization was completely absent in wounds chronically exposed to TXA concentrations of 25 mg/ml or above, and 50–100 mg/ml induced epidermolysis of normal epithelium, possibly by a non‐toxic mechanism. Wound re‐epithelialization was slightly delayed, but not impaired, by limited exposure to 100 mg/ml or chronic exposure to 6·25 mg/ml.ConclusionAlthough short exposure to even high concentrations of topical TXA seems well tolerated in vitro, prolonged exposure can be cytotoxic and may affect wound re‐epithelialization. Surgeons should adjust the TXA concentration to the planned mode of topical administration in clinical practice. Surgical relevanceTopical tranexamic acid (TXA) may reduce bleeding from surgical wounds similarly to intravenous administration without the risk of systemic effects. Little is known, however, regarding the adverse effects of TXA on exposed tissues.We exposed in vitro human keratinocytes and fibroblasts and an ex vivo human skin wound model to TXA at various concentrations and time intervals and found that short exposure to even high concentrations or prolonged exposure to low concentrations of TXA was well tolerated. Prolonged exposure to increasing concentrations increased keratinocyte and fibroblast toxicity, and TXA concentrations of 25 mg/ml or above completely prevented wound‐re‐epithelialization.Prolonged exposure to high concentrations of topical TXA may exert unwanted local tissue effects. This study suggests that surgeons should adjust TXA concentration to the planned mode of topical administration in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity and effect on wound re‐epithelialization after topical administration of tranexamic acid

et al. 2019

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“…It was reported that commercially available fibrin gel would disintegrate within 7 days, but such a rapid degradation could be delayed by seeding cells and adding fibrinolytic inhibitors, such as tranexamic acid, aprotonin, and galardin [62-64]. PRP-tranexamic acid gel seeded with chondrocytes could maintain stability in vitro for 4 weeks without any shrinkage, while cells remained viable and were able to migrate [64].…”

Section: Effect Of Platelet-rich Plasma On Cellsmentioning

confidence: 99%

“…PRP-tranexamic acid gel seeded with chondrocytes could maintain stability in vitro for 4 weeks without any shrinkage, while cells remained viable and were able to migrate [64]. The seeded chondrocytes likely produced abundant ECM, in a manner commensurate with scaffold degradation [62].…”

Section: Effect Of Platelet-rich Plasma On Cellsmentioning

confidence: 99%

Biology of platelet-rich plasma and its clinical application in cartilage repair

2014

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Platelet-rich plasma (PRP) is an autologous concentrated cocktail of growth factors and inflammatory mediators, and has been considered to be potentially effective for cartilage repair. In addition, the fibrinogen in PRP may be activated to form a fibrin matrix to fill cartilage lesions, fulfilling the initial requirements of physiological wound healing. The anabolic, anti-inflammatory and scaffolding effects of PRP based on laboratory investigations, animal studies, and clinical trials are reviewed here. In vitro, PRP is found to stimulate cell proliferation and cartilaginous matrix production by chondrocytes and adult mesenchymal stem cells (MSCs), enhance matrix secretion by synoviocytes, mitigate IL-1β-induced inflammation, and provide a favorable substrate for MSCs. In preclinical studies, PRP has been used either as a gel to fill cartilage defects with variable results, or to slow the progression of arthritis in animal models with positive outcomes. Findings from current clinical trials suggest that PRP may have the potential to fill cartilage defects to enhance cartilage repair, attenuate symptoms of osteoarthritis and improve joint function, with an acceptable safety profile. Although current evidence appears to favor PRP over hyaluronan for the treatment of osteoarthritis, the efficacy of PRP therapy remains unpredictable owing to the highly heterogeneous nature of reported studies and the variable composition of the PRP preparations. Future studies are critical to elucidate the functional activity of individual PRP components in modulating specific pathogenic mechanisms.

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“…At present, the interaction between these important periarticular tissues and TXA remains largely unknown, with rodent and human in vitro studies on chondrocytes providing conflicting results. 13-17 Adult tendon and, in particular, cartilage have a poor regenerative capacity and therefore significant damage to these tissues may be devastating to the patient. 18,19…”

Section: Introductionmentioning

confidence: 99%

Tranexamic acid toxicity in human periarticular tissues

McLean

McCall

Smith

et al. 2019

Bone & Joint Research

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ObjectivesTranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations.MethodsTendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death.ResultsThere was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues.ConclusionThe current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations.Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11–18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1.

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PRP-fibrinogen gel-like chondrocyte carrier stabilized by TXA-preliminary study

Cited by 19 publications

References 16 publications

Cytotoxicity and effect on wound re‐epithelialization after topical administration of tranexamic acid

Cytotoxicity and effect on wound re‐epithelialization after topical administration of tranexamic acid

Biology of platelet-rich plasma and its clinical application in cartilage repair

Tranexamic acid toxicity in human periarticular tissues

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