Micrometer scale guidance of mesenchymal stem cells to form structurally oriented large-scale tissue engineered cartilage

Abstract

Current clinical methods to treat articular cartilage lesions provide temporary relief of the symptoms but fail to permanently restore the damaged tissue. Tissue engineering, using mesenchymal stem cells (MSCs) combined with scaffolds and bioactive factors, is viewed as a promising method for repairing cartilage injuries. However, current tissue engineered constructs display inferior mechanical properties compared to native articular cartilage, which could be attributed to the lack of structural organization of the extracellular matrix (ECM) of these engineered constructs in comparison to the highly oriented structure of articular cartilage ECM. We previously showed that we can guide MSCs undergoing chondrogenesis to align using microscale guidance channels on the surface of a two-dimensional (2-D) collagen scaffold, which resulted in the deposition of aligned ECM within the channels and enhanced mechanical properties of the constructs. In this study, we developed a technique to roll 2-D collagen scaffolds containing MSCs within guidance channels in order to produce a large-scale, three-dimensional (3-D) tissue engineered cartilage constructs with enhanced mechanical properties compared to current constructs. After rolling the MSC-scaffold constructs into a 3-D cylindrical structure, the constructs were cultured for 21 days under chondrogenic culture conditions. The microstructure architecture and mechanical properties of the constructs were evaluated using imaging and compressive testing. Histology and immunohistochemistry of the constructs showed extensive glycosaminoglycan (GAG) and collagen type II deposition. Second harmonic generation imaging and Picrosirius red staining indicated alignment of neo-collagen fibers within the guidance channels of the constructs. Mechanical testing indicated that constructs containing the guidance channels displayed enhanced compressive properties compared to control constructs without these channels. In conclusion, using a novel roll-up method, we have developed large scale MSC based tissue-engineered cartilage that show microscale structural organization and enhanced compressive properties compared to current tissue engineered constructs.

Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model

“…Articular cartilage defects are very common due to the increasing numbers of patients with traumatic injuries and osteoarthritis (OA) [ 1 ]. Cartilage naturally lacks a blood supply and nerves [ 2 ]. Hence, the repair of cartilage lesions is very difficult due to the poor healing capacity.…”

Aligned electrospun cellulose scaffolds coated with rhBMP-2 for both in vitro and in vivo bone tissue engineering

“…The change in cell adhesion and elongated cellular morphology on nanofibrous scaffolds can be explained by the classical theory of contact guidance (Jamaiyar et al, 2017). Aligned nanofibers have recently been explored to employ spatial instruction for different stem cells types, such as endothelial cells (Chou et al, 2017), neuronal cells (Hyysalo, Ristola, Joki, Honkanen, Vippola & Narkilahti, 2017), cardiomyocytes (Wanjare, Hou, Nakayama, Kim, Mezak & Abilez, 2017), and BMSCs (Perikamana et al, 2015). When BMSCs were cultured on aligned poly(L-lactic acid) (PLLA) nanofibers, the same morphological changes were observed as we reported (Perikamana et al, 2015).…”

An injectable, click-crosslinked, cytomodulin-modified hyaluronic acid hydrogel for cartilage tissue engineering

“…Cartilage tissue engineering is considered a promising modality for effective repair of damaged cartilage tissue 7,8 . The procedure most often used in cartilage tissue engineering involves a suitable combination of seeded cells, a biocompatible scaffold, and biological factors that support cartilage formation.…”