Biochemical Stimulus-Based Strategies for Meniscus Tissue Engineering and Regeneration

Abstract

Meniscus injuries are very common and still pose a challenge for the orthopedic surgeon. Meniscus injuries in the inner two-thirds of the meniscus remain incurable. Tissue-engineered meniscus strategies seem to offer a new approach for treating meniscus injuries with a combination of seed cells, scaffolds, and biochemical or biomechanical stimulation. Cell- or scaffold-based strategies play a pivotal role in meniscus regeneration. Similarly, biochemical and biomechanical stimulation are also important. Seed cells and scaffolds can be used to construct a tissue-engineered tissue; however, stimulation to enhance tissue maturation and remodeling is still needed. Such stimulation can be biomechanical or biochemical, but this review focuses only on biochemical stimulation. Growth factors (GFs) are one of the most important forms of biochemical stimulation. Frequently used GFs always play a critical role in normal limb development and growth. Further understanding of the functional mechanism of GFs will help scientists to design the best therapy strategies. In this review, we summarize some of the most important GFs in tissue-engineered menisci, as well as other types of biological stimulation.

Preparation of Decellularized Bovine Tendon Scaffold and Evaluation of Its Interaction with Adipose Tissue-Derived Mesenchymal Stem Cells

“…Injury during sports activities is the most crucial problem that leads to the obligatory retirement of athletes. Tendon injuries are one of the most common injuries, and if they are acute, they can cause the inability to move, endanger physical health, increase medical costs, and reduce athletes' motivation (26). Therefore, the preparation of natural tendon scaffolds for therapeutic activities is of great importance in this field (27).…”

Microstructure Analysis and Reconstruction of a Meniscus

“…To overcome these limitations, different kinds of tissue‐engineered scaffolds have been developed 6, 7 , including using biomaterials to fabricate porous scaffolds, seeding cells on the scaffold, and adding growth factors for cell proliferation and differentiation 8 . A functional, tissue‐engineered scaffold should mimic the biomechanical structure of the meniscus and have appropriate mechanical properties to bear stress from different directions 9 .…”

Engineering Anisotropic Meniscus: Zonal Functionality and Spatiotemporal Drug Delivery

“…(i) stimulating cell migration, especially needed for acellular scaffolds to recruit endogenous cells towards the defect area 3,13 ; (ii) promoting cell proliferation and chondrogenic differentiation 3,13,14 , (iii) activating anabolic pathways involved in meniscal ECM synthesis 3 , (iv) supporting angiogenesis 15 , and/or (v) stimulating a controlled tissue degradation to enhance cell penetration 10 .…”

“…Of all the GFs, the transforming growth factor-β (TGF-β) superfamily (particularly TFG-β1, TFG-β3, bone morphogenic protein-2 (BMP-2) and bone morphogenic protein-7 (BMP-7)), the basic fibroblast growth factor (bFGF), and the insulin-like growth factor-1 (IGF-1) are the ones that have been most thoroughly investigated for meniscal regeneration. For an extensive reading about the GFs employed in meniscal TE we refer to a recent review on the topic 14 .…”

“…Considering the heterogeneous structure of the meniscus and the different cell types involved in its formation, achieving a successful meniscal regeneration poses a big challenge, that may require the delivery of multiple GFs with different release kinetics. In fact, examples of synergistic effects between GFs, such as bFGF and TGF-β3; IGF-1 and TGF-β1; connective tissue growth factor (CTGF) and TGF-β3 have been reported 14 , and the exploitation of these synergies seems to be the direction this field will go as it evolves.…”