Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering In addition, the biology of cartilage and the bony ECM is also summarized Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed

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Injectable hydrogels for cartilage and bone tissue engineering.

An injectable, self-healing hydrogel (≈1.5 kPa) is developed for healing nerve-system deficits. Neurosphere-like progenitors proliferate in the hydrogel and differentiate into neuron-like cells. In the zebrafish injury model, the central nervous system function is partially rescued by injection of the hydrogel and significantly rescued by injection of the neurosphere-laden hydrogel. The self-healing hydrogel may thus potentially repair the central nervous system.

An Injectable, Self‐Healing Hydrogel to Repair the Central Nervous System

Cell-material interactions constitute a key fundamental topic in biomaterials study. Various cell cues and matrix cues as well as soluble factors regulate cell behaviors on materials. These factors are coupled with each other as usual, and thus it is very difficult to unambiguously elucidate the role of each regulator. The recently developed material techniques of surface patterning afford unique ways to reveal the underlying science. This paper reviews the pertinent material techniques to fabricate patterns of microscale and nanoscale resolutions, and corresponding cell studies. Some issues are emphasized, such as cell localization on patterned surfaces of chemical contrast, and effects of cell shape, cell size, cell-cell contact, and seeding density on differentiation of stem cells. Material cues to regulate cell adhesion, cell differentiation and other cell events are further summed up. Effects of some physical properties, such as surface topography and matrix stiffness, on cell behaviors are also discussed; nanoscaled features of substrate surfaces to regulate cell fate are summarized as well. The pertinent work sheds new insight into the cell-material interactions, and is stimulating for biomaterial design in regenerative medicine, tissue engineering, and high-throughput detection, diagnosis, and drug screening.

Cell–Material Interactions Revealed Via Material Techniques of Surface Patterning

Recent Progress on Circularly Polarized Luminescent Materials for Organic Optoelectronic Devices

Mesenchymal stem cells (MSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and expanded as plastic adherent cells, MSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates reminiscent of skeletal condensation in vivo. Recent studies have shown that MSC 3D aggregation improved a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. Hence, the formation of 3D MSC aggregates has been explored as a novel strategy to improve cell delivery, functional activation, and in vivo retention to enhance therapeutic outcomes. This article summarizes recent reports of MSC aggregate self-assembly, characterization of biological properties, and their applications in preclinical models. The cellular and molecular mechanisms underlying MSC aggregate formation and functional activation are discussed, and the areas that warrant further investigation are highlighted. These analyses are combined to provide perspectives for identifying the controlling mechanisms and refining the methods of aggregate fabrication and expansion for clinical applications.

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Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

In this study, a multi-benzaldehyde functionalized poly(ethylene glycol) analogue, poly(ethylene oxide-co-glycidol)-CHO (poly(EO-co-Gly)-CHO), was designed and synthesized for the first time, and was applied as a cross-linker to develop an injectable hydrogel system. Simply mixing two aqueous precursor solutions of glycol chitosan (GC) and poly(EO-co-Gly)-CHO led to the formation of chemically cross-linked hydrogels under physiological conditions in situ. The cross-linking was attributed to a Schiff's base reaction between amino groups of GC and aldehyde groups of poly(EO-co-Gly)-CHO. The gelation time, water uptake, mechanical properties and network morphology of the GC/poly(EO-co-Gly) hydrogels were well modulated by varying the concentration of poly(EO-co-Gly)-CHO. Degradation of the in situ formed hydrogels was confirmed both in vitro and in vivo. The integrity of the GC/poly(EO-co-Gly) hydrogels was subcutaneously maintained for up to 12 weeks in ICR mice. The feasibility of encapsulating chondrocytes in the GC/poly(EO-co-Gly) hydrogels was assessed. Live/Dead staining assay demonstrated that the chondrocytes were highly viable in the hydrogels, and no dedifferentiation of chondrocytes was observed after 2 weeks of in vitro culture. Cell counting kit-8 assay gave evidence of the remarkably sustained proliferation of the encapsulated chondrocytes. Maintenance of the chondrocyte phenotype was also confirmed with an examination of characteristic gene expression. These features suggest that GC/poly(EO-co-Gly) hydrogels hold potential as an artificial extracellular matrix for cartilage tissue engineering.

An injectable hydrogel formed by in situ cross-linking of glycol chitosan and multi-benzaldehyde functionalized PEG analogues for cartilage tissue engineering

The effect of culture conditions on the adipogenic and osteogenic inductions of mesenchymal stem cells on micropatterned surfaces

Effects of surface molecular chirality on adhesion and differentiation of stem cells

Subcellular cell geometry on micropillars regulates stem cell differentiation.

Functional groups of materials are known to affect cell behaviors, yet the corresponding effect on stem cell differentiation is always coupled with that of cell spreading; it is thus unclear whether the chemical groups influence cell differentiation directly or via cell spreading indirectly. Herein we used a unique surface patterning technique to decouple the corresponding effects. Mesenchymal stem cells (MSCs) derived from bone marrow were seeded on surfaces coated with alkanethiols with one of four functional end groups (−CH3, −OH, −COOH, and −NH2) and underwent 9 days of chondrogenic induction. The measurements of quartz crystal microbalance with dissipation confirmed less proteins adsorbed from the cell culture media on the neutral −CH3 and −OH surfaces than on the charged −COOH and −NH2 surfaces. The neutral surfaces exhibited less cell spreading and higher extents of chondrogenic differentiation than the charged surfaces, according to the characterizations of immunofluorescence staining and quantita...

Effects of Functional Groups of Materials on Nonspecific Adhesion and Chondrogenic Induction of Mesenchymal Stem Cells on Free and Micropatterned Surfaces.

Bin Cao

Papers

An injectable hydrogel formed by in situ cross-linking of glycol chitosan and multi-benzaldehyde functionalized PEG analogues for cartilage tissue engineering

The effect of culture conditions on the adipogenic and osteogenic inductions of mesenchymal stem cells on micropatterned surfaces

Effects of surface molecular chirality on adhesion and differentiation of stem cells

Subcellular cell geometry on micropillars regulates stem cell differentiation.

Effects of Functional Groups of Materials on Nonspecific Adhesion and Chondrogenic Induction of Mesenchymal Stem Cells on Free and Micropatterned Surfaces.