Deciphering Mechanical Regulation of Chondrogenesis in Fibrin–Polyurethane Composite Scaffolds Enriched with Human Mesenchymal Stem Cells: A Dual Computational and Experimental Approach

Abstract

Fibrin-polyurethane composite scaffolds support chondrogenesis of human mesenchymal stem cells (hMSCs) derived from bone marrow and due to their robust mechanical properties allow mechanical loading in dynamic bioreactors, which has been shown to increase the chondrogenic differentiation of MSCs through the transforming growth factor beta pathway. The aim of this study was to use the finite element method, mechanical testing, and dynamic in vitro cell culture experiments on hMSC-enriched fibrin-polyurethane composite scaffolds to quantitatively decipher the mechanoregulation of chondrogenesis within these constructs. The study identified compressive principal strains as the key regulator of chondrogenesis in the constructs. Although dynamic uniaxial compression did not induce chondrogenesis, multiaxial loading by combined application of dynamic compression and interfacial shear induced significant chondrogenesis at locations where all the three principal strains were compressive and had a minimum magnitude of 10%. In contrast, no direct correlation was identified between the level of pore fluid velocity and chondrogenesis. Due to the high permeability of the constructs, the pore fluid pressures could not be increased sufficiently by mechanical loading, and instead, chondrogenesis was induced by triaxial compressive deformations of the matrix with a minimum magnitude of 10%. Thus, it can be concluded that dynamic triaxial compressive deformations of the matrix is sufficient to induce chondrogenesis in a thresholddependent manner, even where the pore fluid pressure is negligible.

Asymmetrical seeding of MSCs into fibrin-poly(ester-urethane) scaffolds and its effect on mechanically induced chondrogenesis

“…In Uniform scaffolds, where all cells seeded within the scaffold were labelled, the labelled MSCs were present around the four edges of the scaffold but not within the centre of the scaffold (Figure ). Previous work in this model system has shown homogeneous seeding of scaffolds immediately after seeding and at day 7 of culture (Zahedmanesh et al ., ); therefore, the loss of cells from the centre of the scaffolds appears to occur as a result of longer periods of culture.…”

“…Seeding a cell layer of MSCs on a three‐dimensional construct containing chondrocytes has also been shown to improve construct properties (Mesallati et al ., ). This need for anisotropy is even more important in loaded environments; for example, in the loading system used in this work, because the distribution of multicomponent strain – critical in the induction of chondrogenesis – can vary throughout the scaffold (Zahedmanesh et al ., ).…”

“…Loaded scaffolds were exposed to 20 cycles of 10% compression superimposed on top of a 10% pre‐strain and shear loading (± 25°) at 1Hz for 1 h a day, five times a week. The application of multi‐axial mechanical load to fibrin–poly(ester‐urethane) scaffolds in this system has been described previously (Zahedmanesh et al ., ).…”

Regenerative rehabilitation: The role of mechanotransduction in orthopaedic regenerative medicine

“…Work is in progress to develop an osteochondral defect model that can be subjected to multiaxial load. This is an area where finite element analysis (FEA) models could accelerate knowledge, providing predictive outcome measures that can be defined . Models that can take into account the patient specific injury and load distribution could be used to establish the load patterns experienced by the injury site.…”

Critical Review on the Physical and Mechanical Factors Involved in Tissue Engineering of Cartilage

“…Studies have combined natural polymers [63,64] as well as mixing natural and synthetic polymers [65]. Composite scaffolds allow for the creation of more complex geometries and better functional properties more representative of AC in order to support enhanced cell adhesion, proliferation and dif- Collagen [63,103,104] Poly(ethylene) glycol [61,105] Chitosan [106,107] Gelatin-hydroxyphenylpropionic acid [71] Fibrin [54,56,108,109] Poly(caprolactone) [110,111] Alginate [53,64] Self-assembling peptides [68,70,72,73] Hyaluronic acid [55,64,108] poly(l-lactive acid) [67,111] Agarose and gellan gum…”