Shape-Configurable Mesh for Hernia Repair by Synchronizing Anisotropic Body Motion.

Continuous progress has been made in elucidating the relationship between material property, device design, and body function to develop surgical meshes. However, an unmet need still exists wherein the surgical mesh can handle the body motion and thereby promote the repair process. Here, the hernia mesh design and the advanced polymer properties are tailored to synchronize with the anisotropic abdominal motion through shape configuration. The thermomechanical property of shape configurable polymer enables molding of mesh shape to fit onto the abdominal structure upon temperature shift, followed by shape fixing with the release of the heat energy. The microstructural design of mesh is produced through finite element modeling to handle the abdominal motion efficiently through the anisotropic longitudinal and transverse directions. The design effects are validated through in vitro, ex vivo, and in vivo mechanical analyses using a self-configurable, body motion responsive (BMR) mesh. The regenerative function of BMR mesh leads to effective repair in a rat hernioplasty model by effectively handling the anisotropic abdomen motion. Subsequently, the device-tissue integration is promoted by promoting healthy collagen synthesis with fibroblast-to-myofibroblast differentiation. This study suggests a potential solution to promote hernia repair by fine-tuning the relationship between material property and mesh design.

Chiral Cell Nanomechanics Originated in Clockwise/Counterclockwise Biofunctional Microarrays to Govern the Nuclear Mechanotransduction of Mesenchymal Stem Cells.

Cell chirality is extremely important for the evolution of cell morphogenesis to manipulate cell performance due to left-right asymmetry. Although chiral micro- and nanoscale biomaterials have been developed to regulate cell functions, how cell chirality affects cell nanomechanics to command nuclear mechanotransduction was ambiguous. In this study, chiral engineered microcircle arrays were prepared by photosensitive cross-linking synthesis on cell culture plates to control the clockwise/counterclockwise geometric topology of stem cells. Asymmetric focal adhesion and cytoskeleton structures could induce chiral cell nanomechanics measured by atomic force microscopy (AFM) nanoindentation in left-/right-handed stem cells. Cell nanomechanics could be enhanced when the construction of mature focal adhesion and the assembly of actin and myosin cytoskeletons were well organized in chiral engineered stem cells. Curvature angles had a negative effect on cell nanomechanics, while cell chirality did not change cytoskeletal mechanics. The biased cytoskeleton tension would engender different nuclear mechanotransductions by yes-associated protein (YAP) evaluation. The chiral stimuli were delivered into the nuclei to oversee nuclear behaviors. A strong cell modulus could activate high nuclear DNA synthesis activity by mechanotransduction. The results will bring the possibility of understanding the interplay of chiral cell nanomechanics and mechanotransduction in nanomedicines and biomaterials.

Interconnected collagen porous scaffolds prepared with sacrificial PLGA sponge templates for cartilage tissue engineering.

Interconnected pore structures of scaffolds are important to control the cell functions for cartilage tissue engineering. In this study, collagen scaffolds with interconnected pore structures were prepared using poly(D,L-lactide-co-glycolide) (PLGA) sponges as sacrificial templates. Six types of PLGA sponges of different pore sizes and porosities were prepared by the solvent casting/particulate leaching method and used to regulate the interconnectivity of the collagen scaffolds. The integral and continuous templating structure of PLGA sponges generated well-interconnected pore structures in the collagen scaffolds. Bovine articular chondrocytes cultured in collagen scaffolds showed homogenous distribution, fast proliferation, high expression of cartilaginous genes and high secretion of cartilaginous extracellular matrix. In particular, the collagen scaffold templated by the PLGA sacrificial sponge that was prepared with a high weight ratio of PLGA and large salt particulates showed the most promotive effect on cartilage tissue formation. The interconnected pore structure facilitated cell distribution, cell-cell interaction and cartilage tissue regeneration.

PLGA-collagen-ECM hybrid meshes mimicking stepwise osteogenesis and their influence on the osteogenic differentiation of hMSCs.

Extracellular matrices (ECMs) are dynamically altered and remodeled during tissue development. How the dynamic remodeling of ECM affects stem cell functions remains poorly understood due to the difficulty of obtaining biomimetic ECMs. In this study, stepwise osteogenesis-mimicking ECM-deposited hybrid meshes were prepared by culturing human mesenchymal stem cells (hMSCs) in poly (lactic-co-glycolic acid) (PLGA)-collagen hybrid meshes and controlling the stages of the osteogenesis of hMSCs. Three types of hybrid mesh mimicking the ECMs that were secreted from stem cell stage of hMSCs (SC-ECM), early stage (EO-ECM) and late stage (LO-ECM) osteogenesis of hMSCs were prepared. The stepwise osteogenesis-mimicking ECM deposited PLGA-collagen hybrid meshes showed different ECM compositions associated with the stage of osteogenesis. Their effects on the osteogenic differentiation of hMSCs differed. EO-ECM scaffold increased and LO-ECM scaffold moderately promoted the osteogenic differentiation of hMSCs. However, SC-ECM scaffold inhibited the osteogenic differentiation of hMSCs. The novel PLGA-collagen-ECM hybrid meshes will provide useful tools for stem cell culture and tissue engineering.

PLGA-collagen-ECM hybrid scaffolds functionalized with biomimetic extracellular matrices secreted by mesenchymal stem cells during stepwise osteogenesis-co-adipogenesis.

A shift in osteogenesis toward adipogenesis of human bone marrow-derived mesenchymal stem cells (hMSCs) is a crucial pathological factor in the progression of osteoporosis. The development of an in vitro three-dimensional (3D) model that reflects the dynamic remodeling of extracellular matrices (ECMs) during simultaneous osteogenesis and adipogenesis of hMSCs can provide a useful tool to mimic the process and to investigate how 3D ECMs balance the osteogenic and adipogenic differentiation of hMSCs. In this study, ECMs secreted by hMSCs during their stepwise osteogenesis-co-adipogenesis were deposited on hybrid meshes of poly(lactide-co-glycolide) (PLGA) and collagen to prepare biomimetic PLGA-collagen-ECM hybrid scaffolds. Four types of stepwise differentiation ECMs were prepared: ECMs secreted by hMSCs at early stages of osteogenesis and adipogenesis (EOEA-ECMs), hMSCs at early stages of osteogenesis and late stages of adipogenesis (EOLA-ECMs), hMSCs at late stages of osteogenesis and early stages of adipogenesis (LOEA-ECMs) and hMSCs at late stages of osteogenesis and late stages of adipogenesis (LOLA-ECMs). The deposited ECMs had different compositions that were dependent on the different stages of osteogenesis and adipogenesis. They also showed different effects on balancing the adipogenic and osteogenic differentiation of hMSCs. The EOEA-ECM scaffold had a promotive effect on adipogenesis and a suppressive effect on the osteogenesis of hMSCs. The LOEA-ECM and LOLA-ECM scaffolds showed a promotive effect on osteogenesis and a moderate effect on the adipogenic differentiation of hMSCs. The EOLA-ECM scaffold exhibited a suppressive effect on both osteogenesis and adipogenesis of hMSCs. However, the EOLA-ECM scaffold promoted hMSC proliferation more strongly than the other ECM scaffolds. The results indicated that dynamically remodeling ECM scaffolds could affect the osteogenic and adipogenic differentiation of hMSCs and should provide a useful 3D cell culture model for the investigation of ECM-cell interactions.