Scaffolds Derived from ECM Produced by Chondrogenically Induced Human MSC Condensates Support Human MSC Chondrogenesis

Abstract

Osteoarthritis is a leading cause of disability affecting an increasing number of individuals. However, cartilage replacement therapies are inadequate, and better cartilage regeneration products must be developed. In this work, we describe a human mesenchymal stem cell (hMSC)-based approach for fabricating extracellular matrix (ECM) scaffolds from tissueengineered cartilage sheets and then for inducing chondrogenesis of reseeded hMSCs within the ECM scaffolds. Two types of ECM scaffolds were fabricated: one from high-density hMSC sheets cultured with media-supplemented transforming growth factor beta-1 (TGF-β1; −MS) and the other from high-density hMSC sheets incorporated with TGF-β1-laden gelatin microspheres (+MS), which significantly enhance chondrogenesis within the sheet system. Interestingly, when scaffolds were reseeded with hMSCs, −MS scaffolds lead to significantly more glycosaminoglycan (GAG) accumulation than +MS scaffolds. Importantly, ECM scaffolds could be soak loaded with TGF-β1 to produce cartilage of similar quality as that of constructs cultured with TGF-β1 in the media, thereby removing the need for supplementing the media with the growth factor. Lastly, tissues formed with the scaffolds were larger with more uniform cartilage matrix elaboration compared to scaffold-free groups making this strategy a clinically promising auto-or allogeneic therapy.

Fiber Reinforced Cartilage ECM Functionalized Bioinks for Functional Cartilage Tissue Engineering

“…To successfully engineer cartilage‐like tissue using MSCs, it is critical to develop biomaterials that i) provide a microenvironment conducive to a stable chondrogenic phenotype, ii) provide mechanical integrity, and iii) possess the capacity to deliver growth factors and other regulatory biomolecules. In an effort to engineer cartilage‐mimetic biomaterials favorable to chondrogenesis, a number of studies have investigated the chondro‐inductivity of natural polymer scaffolds generated from and/or functionalized with commercially available collagens (typically type I or type II), hyaluronic acid, chondroitin sulfate and decellularized cartilage extracellular matrix (cECM) . While such ECM derived biomaterials are generally supportive of a chondrogenic phenotypic, they typically lack the mechanical properties for functioning in high load bearing environments.…”

Functionality of decellularized matrix in cartilage regeneration: A comparison of tissue versus cell sources

“…Recent evidence showed that, different from T-dECMs that induce chondrogenic differentiation directly, dECMs derived from chondrocyte/stem cells (C-dECMs) benefited cartilage regeneration by promoting expanded cell proliferation and chondrogenic potential [25,[27][28][29][30][31][32]. However, few review papers are available comparing the differences between these two dECMs when they serve as substrates for cartilage regeneration.…”

Living cell-only bioink and photocurable supporting medium for printing and generation of engineered tissues with complex geometries

“…Lacunae structures were also observed in sectioned slides of chondrogenically differentiated constructs ( Fig. 4h), indicating maturation of cartilage tissues 25 . Successful tissue formation by the 3D printed hMSCs were further confirmed by quantification of osteogenic (i.e., alkaline phosphatase (ALP) activity and calcium deposition) and chondrogenic (i.e., glycosaminoglycan (GAG) production) markers ( Fig.…”