University of California Irvine School of Medicine, Irvine, California, USA.
Department of Biomedical Engineering, University of California Irvine, Irvine, California, USA.
Am J Sports Med. 2021 Apr;49(5):1305-1312. doi: 10.1177/0363546521995184. Epub 2021 Mar 5.
Although the toxic effects of bupivacaine on chondrocyte monolayer culture have been well described, its cellular and mechanical effects on native and engineered articular cartilage remain unclear. For the repair of articular cartilage defects, fresh autologous and allogenic cartilage grafts are commonly used, and engineered cell-based therapies are emerging. The outcome of grafting therapies aimed at repairing damaged cartilage relies largely on maintaining proper viability and mechanical suitability of the donor tissues.
To investigate the in vitro effects of single bupivacaine exposure on the viability and mechanics of 2 cartilage graft types: native articular cartilage and engineered neocartilage.
Controlled laboratory study.
Articular cartilage explants were harvested from the bovine stifle femoral condyles, and neocartilage constructs were engineered from bovine stifle chondrocytes using the self-assembling process, a scaffold-free approach to engineer cartilage tissue. Both explants and neocartilage were exposed to chondrogenic medium containing a clinically applicable bolus of 0.5%, 0.25%, or 0% (control) bupivacaine for 1 hour, followed by fresh medium wash and exchange. Cell viability and matrix content (collagen and glycosaminoglycan) were assessed at = 24 hours after treatment, and compressive mechanical properties were assessed with creep indentation testing at = 5 to 6 days after treatment.
Single bupivacaine exposure was chondrotoxic in both explants and neocartilage, with 0.5% bupivacaine causing a significant decrease in chondrocyte viability compared with the control condition (55.0% ± 13.4% vs 71.9% ± 13.5%; < .001). Bupivacaine had no significant effect on matrix content for either tissue type. There was significant weakening of the mechanical properties in the neocartilage when treated with 0.5% bupivacaine compared with control, with decreased aggregate modulus (415.8 ± 155.1 vs 660.3 ± 145.8 kPa; = .003), decreased shear modulus (143.2 ± 14.0 vs 266.5 ± 89.2 kPa; = .002), and increased permeability (14.7 ± 8.1 vs 6.6 ± 1.7 × 10 m/Ns; = .009). Bupivacaine exposure did not have a significant effect on the mechanical properties of native cartilage explants.
Single bupivacaine exposure resulted in significant chondrotoxicity in native explants and neocartilage and significant weakening of mechanical properties of neocartilage. The presence of abundant extracellular matrix does not appear to confer any additional resistance to the toxic effects of bupivacaine.
Clinicians should be judicious regarding the use of intra-articular bupivacaine in the setting of articular cartilage repair.
虽然布比卡因对软骨细胞单层培养的毒性作用已得到很好的描述，但它对天然和工程化关节软骨的细胞和机械作用仍不清楚。对于关节软骨缺损的修复，通常使用新鲜的自体和同种异体软骨移植物，并且新兴的工程细胞疗法。旨在修复受损软骨的移植物治疗的结果在很大程度上取决于维持供体组织的适当活力和机械适应性。
研究单次布比卡因暴露对 2 种软骨移植物类型（天然关节软骨和工程化新软骨）的活力和力学性能的体外影响。
对照实验室研究。
从牛膝关节股骨髁中采集关节软骨标本，并使用自组装过程从牛膝关节软骨细胞中工程化构建新软骨，这是一种无支架方法来构建软骨组织。标本和新软骨均暴露于含有临床应用的 0.5%、0.25%或 0%（对照）布比卡因的软骨形成培养基中 1 小时，然后用新鲜培养基冲洗和交换。处理后 24 小时评估细胞活力和基质含量（胶原和糖胺聚糖），处理后 5-6 天通过蠕变压痕测试评估压缩力学性能。
单次布比卡因暴露对标本和新软骨均具有软骨毒性作用，0.5%布比卡因与对照相比显著降低软骨细胞活力（55.0%±13.4%比 71.9%±13.5%； <.001）。布比卡因对两种组织类型的基质含量均无显著影响。与对照相比，用 0.5%布比卡因处理的新软骨的机械性能明显减弱，聚集弹性模量降低（415.8±155.1 比 660.3±145.8 kPa； =.003），剪切弹性模量降低（143.2±14.0 比 266.5±89.2 kPa； =.002），渗透率增加（14.7±8.1 比 6.6±1.7×10 m/Ns； =.009）。布比卡因暴露对天然软骨标本的机械性能没有显著影响。
单次布比卡因暴露会导致天然标本和新软骨的明显软骨毒性，并显著削弱新软骨的力学性能。丰富的细胞外基质的存在似乎不会对布比卡因的毒性作用产生任何额外的抵抗力。
在关节软骨修复的情况下，临床医生应慎重使用关节内布比卡因。
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