Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

Abstract

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS – which was released from scaffolds quickly – significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

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.…”

Hypoxia impacts human MSC response to substrate stiffness during chondrogenic differentiation

“…For cartilage, which has a very poor capacity for self-repair in the adult, much of what is known about the conditions that foster cartilage formation come from developmental studies, including the study of limb bud development and endochondral ossification in the axial skeleton. Cartilage TE strategies that mimic both the biochemical milieu as well as the mechanical environment that native cells experience during these developmental processes may yield engineered constructs that can repair damaged adult tissues [6] , [7] , [8] , [9] .…”

Structural and Functional Properties of Neocartilage Construct Engineered in Poly (Lactic-co-Glycolic Acid) (PLGA) based Scaffolds

“…One of the characteristics of a good scaffold is it can provide en ough mechanical strength as an initial support for the neo-tissue formation [21]. This is perhaps due to the atelocollagen that promotes the secretion of collagen within the cells [22]. The secretion of ECM contributes to the mechanical strength of the scaffolds [19].…”