3D biomaterial P scaffolds carrying umbilical cord mesenchymal stem cells improve biointegration of keratoprosthesis.

Biointegration of a keratoprosthesis (KPro) is critical for the device stability and long-term retention. Biointegration of the KPro device and host tissue takes place between the surrounding corneal graft and the central optic (made by poly (methyl methacrylate)). Our previous clinical results showed that auricular cartilage reinforcement is able to enhance the KPro biointegration. However, the auricular cartilage is non-renewable and difficult to acquire. In this study, we developed a novel type of biomaterial using a three-dimensional porous polyethylene glycol acrylate scaffold (3D biological P-scaffold) carrier with chondrocytes differentiated from induced human umbilical cord mesenchymal stem cells (hUC-MSCs) and tested in rabbit corneas. The results showed hUC-MSCs bear stem cell properties and coule be induced into chondrocytes, P-scaffold is beneficial to the growth and differentiation of hUC-MSCs bothin vivoandin vitro. Besides, after implanting the P-scaffold into the corneal stroma, no serious immune rejection response, such as corneal ulcer or perforation were seen, suggested a good biocompatibility of P-scaffold with the corneal tissue. Moreover, after implanting P-scaffold in together with the differentiated chondrocytes into the rabbit corneal stroma, they significantly increased corneal thickness and strengthened the host cornea, and chondrocytes could stably persist inside the cornea. In summary, the 3D biological P-scaffold carrying differentiated hUC-MSCs could be the preferable material for KPro reinforcement.

Cryoprotectant enables structural control of porous scaffolds for exploration of cellular mechano-responsiveness in 3D.

Despite the wide applications, systematic mechanobiological investigation of 3D porous scaffolds has yet to be performed due to the lack of methodologies for decoupling the complex interplay between structural and mechanical properties. Here, we discover the regulatory effect of cryoprotectants on ice crystal growth and use this property to realize separate control of the scaffold pore size and stiffness. Fibroblasts and macrophages are sensitive to both structural and mechanical properties of the gelatin scaffolds, particularly to pore sizes. Interestingly, macrophages within smaller and softer pores exhibit pro-inflammatory phenotype, whereas anti-inflammatory phenotype is induced by larger and stiffer pores. The structure-regulated cellular mechano-responsiveness is attributed to the physical confinement caused by pores or osmotic pressure. Finally, in vivo stimulation of endogenous fibroblasts and macrophages by implanted scaffolds produce mechano-responses similar to the corresponding cells in vitro, indicating that the physical properties of scaffolds can be leveraged to modulate tissue regeneration.

Physical Properties of Implanted Porous Bioscaffolds Regulate Skin Repair: Focusing on Mechanical and Structural Features.

Porous bioscaffolds are applied to facilitate skin repair since the early 1990s, but a perfect regeneration outcome has yet to be achieved. Until now, most efforts have focused on modulating the chemical properties of bioscaffolds, while physical properties are traditionally overlooked. Recent advances in mechanobiology and mechanotherapy have highlighted the importance of biomaterials' physical properties in the regulation of cellular behaviors and regenerative processes. In skin repair, the mechanical and structural features of porous bioscaffolds are two major physical properties that determine therapeutic efficacy. Here, first an overview of natural skin repair with an emphasis on the major biophysically sensitive cell types involved in this multistage process is provided, followed by an introduction of the four roles of bioscaffolds as skin implants. Then, how the mechanical and structural features of bioscaffolds influence these four roles is discussed. The mechanical and structural features of porous bioscaffolds should be tailored to balance the acceleration of wound closure and functional improvements of the repaired skin. This study emphasizes that decoupling and precise control of the mechanical and structural features of bioscaffolds are significant aspects that should be considered in future biomaterial optimization, which can build a foundation to ultimately achieve perfect skin regeneration outcomes.