Current advances in the development of natural meniscus scaffolds: innovative approaches to decellularization and recellularization

Abstract

The increasing rate of injuries to the meniscus indicates the urgent need to develop effective repair strategies. Irreparably damaged menisci can be replaced and meniscus allografts represent the treatment of choice; however, they have several limitations, including availability and compatibility. Another approach is the use of artificial implants but their chondroprotective activities are still not proved clinically. In this situation, tissue engineering offers alternative natural decellularized extracellular matrix (ECM) scaffolds, which have shown biomechanical properties comparable to those of native menisci and are characterized by low immunogenicity and promising regenerative potential. In this article, we present an overview of meniscus decellularization methods and discuss their relative merits. In addition, we comparatively evaluate cell types used to repopulate decellularized scaffolds and analyze the biocompatibility of the existing experimental models. At present, acellular ECM hydrogels, as well as slices and powders, have been explored, which seems to be promising for partial meniscus regeneration. However, their inferior biomechanical properties (compressive and tensile stiffness) compared to natural menisci should be improved. Although an optimal decellularized meniscus scaffold still needs to be developed and thoroughly validated for its regenerative potential in vivo, we believe that decellularized ECM scaffolds are the future biomaterials for successful structural and functional replacement of menisci.

Biological and Mechanical Predictors of Meniscus Function: Basic Science to Clinical Translation

“…Early studies have established proof of concept that scaffold recellularization is possible in vitro. Chondrocyte seeding onto a scaffold led to increased DNA content and collagen content over a 28‐day period, suggesting a synergistic effect by mimicking the cellular organization of tissues . While these results are promising, further comparative studies are required to identify the optimal cell source and cell seeding technique .…”

“…The use of acellular xenograft meniscus is another avenue that is currently being evaluated. Efficient and reproducible decellularization techniques are available that can maintain the protein architecture of the tissue; however, the chondroprotective properties of these scaffolds is yet to be determined . Several methods have been identified for scaffold decellularization, including freeze‐thaw cycling, enzymatic, ionic detergent removal, and sonication.…”

“…Several methods have been identified for scaffold decellularization, including freeze‐thaw cycling, enzymatic, ionic detergent removal, and sonication. While each technique provides unique merits, there are also drawbacks—primarily the loss of protein microstructure, including collagen type II and proteoglycans . An alternative approach is to convert solid meniscus ECM into an injectable hydrogel scaffold.…”

“…However, the loss of protein content (GAGs) observed in other decellularization techniques persists. The cell‐seeded scaffolds represent another approach for meniscus replacement . Early studies have established proof of concept that scaffold recellularization is possible in vitro.…”

Bio-Engineered Meniscus for Tissue Engineering

“…The mechanism of acid& bases in decellularizing tissues is by catalyzing hydrolytic degradation of the biomolecules that able to dissociate the DNA from the ECM and disrupting nucleic acid [23,30]. Chen et al had performed a decellularization of porcine meniscus using five types of acid consist of acetic acid, formic acid, peracetic acid, succinic acid, malic acid and citric acid with different acid immersion incubation time of 2, 4, 6, 8, 10 and 12 hours [31]. The results portrayed that formic acid with 2 h immersion treatment is the most effective because it managed to remove almost 96% of the DNA contents with minor adverse effect on ECM collagens and GAGs [31].…”