High Amplitude Direct Compressive Strain Enhances Mechanical Properties of Scaffold-Free Tissue-Engineered Cartilage

Abstract

Adult cartilage has a limited healing capacity. Damages resulting from disease or injury increase over time and cause severe pain. One approach to reinstate the cartilage function is tissue engineering (TE). However, the generation of TE cartilage is time consuming and expensive and its properties are so far suboptimal. As in vivo cartilage is subject to loading, it is assumed that mechanical stimulation may enhance the quality of TE cartilage. In this study the short-term influence of variable compressive strain amplitudes on mechanical and biochemical properties of scaffold-free TE cartilage was investigated. Primary porcine chondrocytes were isolated, proliferated, redifferentiated, and transferred onto hydroxyapatite carriers, resulting in scaffold-free cartilage-carrier constructs. These constructs were placed in a custom-made bioreactor. Compression amplitudes of 5%, 10%, and 20% were applied. In each experiment four constructs were loaded with dynamic compression (3000 cycles/day, 1 Hz) for 14 days and four constructs served as unloaded control. The cartilage was evaluated biochemically, histological, and mechanically. No difference in glycosaminoglycan or collagen content between the loaded and the control groups was found. However, a positive correlation between compression amplitude and normalized Young's modulus was detected (R(2)=0.59, p<0.001). The highest compression amplitude of 20% had the strongest positive effect on the mechanical properties of the TE cartilage (Young's modulus increase of 241±28% compared to unloaded control). The data presented suggest that preconditioning with higher load amplitudes might be an attractive way of generating stiffer tissue and may help accelerating the cultivation of mechanically competent TE cartilage.

The knee meniscus: Structure–function, pathophysiology, current repair techniques, and prospects for regeneration

“…Mechanical stimulation of scaffold-free and self-assembled tissue has also shown promising results [229, 232, 238]. Self-assembled articular cartilage has been shown to withstand hydrostatic pressures of up to 10 MPa and respond positively by increasing aggregate modulus (96%), Young's modulus (92%), collagen per wet weight (51%) and GAG per wet weight (52%) [235].…”

“…Self-assembled articular cartilage has been shown to withstand hydrostatic pressures of up to 10 MPa and respond positively by increasing aggregate modulus (96%), Young's modulus (92%), collagen per wet weight (51%) and GAG per wet weight (52%) [235]. A somewhat similar study of scaffold-free porcine chondrocyte constructs demonstrated beneficial responses to direct compression stimulation at strain amplitudes of 5-20% [229]. Following this loading, 200-300% increases in construct stiffness and a 250% increase in Young's modulus was measured [229].…”

“…A somewhat similar study of scaffold-free porcine chondrocyte constructs demonstrated beneficial responses to direct compression stimulation at strain amplitudes of 5-20% [229]. Following this loading, 200-300% increases in construct stiffness and a 250% increase in Young's modulus was measured [229]. Since the knee meniscus is also loaded in cyclic direct compression in vivo [43, 239] these results are promising for tissue engineering of the meniscus using scaffold-free self-assembly.…”

Inkjet‐bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging

“…A stress-strain profile was obtained from the load and displacement data at the end of each relaxation phase to determine the unconfined compressive modulus [39].…”

Temporomandi̇bular Eklem Tami̇r Ve Rejenerasyonunda Doku Mühendi̇sli̇ği̇ Uygulamalari

“…Fonksiyonel kıkır-dak, fibrokartilaj ve diğer dokuların oluşumu için uygun olduğu görülmüştür. [67][68][69][70] Self-assembly bu yüzden TME disk doku mühendisliği için bir alternatif olabilir ve uygulanabilir, fakat yapı iskelesi olmayan yapıların hücrelerin yaşanabilirliliğini destekleme ve matriks üretimi konusunda yetersiz olduğu görülmüştür.…”