Does low‐intensity pulsed ultrasound stimulate maturation of tissue‐engineered cartilage?

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Abstract
Traumatic events are a primary cause of local lesions of articular cartilage. Tissue engineered, cartilage‐like structures represent an alternative to current treatment methods. The time necessary for tissue maturation and the mechanical quality of the regenerate at implantation are both critical factors for clinical success. Low‐intensity pulsed ultrasound has proven to accelerate chondrogenesis in vitro. The goal of this study was to evaluate whether low‐intensity pulsed ultrasound is capable of accelerating the process of cartilage maturation and increasing regenerate stability. Hyaline‐like cartilage specimens were generated in vitro and subcutaneously implanted in the backs of nude mice. Twenty‐eight animals received 20 min of low‐intensity pulsed ultrasound treatment daily, and 28 animals received a sham treatment. Specimens were explanted after 1, 3, 6, and 12 weeks, mechanically tested with the use of an indentation test, histologically examined, and processed for RT‐PCR. The Young's moduli significantly increased from 3 to 12 weeks, and at 6 weeks were comparable to those of native articular cartilage. In histological examination, specimens showed neocartilage formation. There was no significant difference between ultrasound‐treated and sham‐treated groups. The mechanical stability of the neocartilage specimens increased with treatment time and reached values of native cartilage after 6 weeks in vivo. Low‐intensity pulsed‐ultrasound stimulation showed no stimulatory effect on tissue maturation. In contrast, ultrasound‐treated specimens showed a reduced Col 2 expression at 1 week and were significantly less stiff compared to native cartilage at 6 and 12 weeks. An acceleration of the maturation of tissue‐engineered neocartilage in a clinical setting by means of low‐intensity pulsed ultrasound therefore appears rather unrealistic. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 68B: 21–28, 2004