A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol-gel transition with spontaneous physical gelation upon heating instead of cooling. If the transition in water takes place below the body temperature and the chemicals are biocompatible and biodegradable, such gelling behavior makes the associated physical gels injectable biomaterials with unique applications in drug delivery and tissue engineering etc. Various therapeutic agents or cells can be entrapped in situ and form a depot merely by a syringe injection of their aqueous solutions at target sites with minimal invasiveness and pain. This tutorial review summarizes and comments on this soft matter, especially thermogelling poly(ethylene glycol)-(biodegradable polyester) block copolymers. The main types of injectable hydrogels are also briefly introduced, including both physical gels and chemical gels.
We herein present a novel platform of well-controlled ordered and disordered nanopatterns positioned with a cyclic peptide of arginine-glycine-aspartic acid (RGD) on a bioinert poly(ethylene glycol) background, to study whether the nanoscopic order of spatial patterning of the integrinspecific ligands influences osteoblast adhesion. This is the first time that the nanoscale order of RGD ligand patterns was varied quantitatively, and tested for its impact on the adhesion of tissue cells. Our findings reveal that integrin clustering and such adhesion induced by RGD ligands is dependent on the local order of ligand arrangement on a substrate when the global average ligand spacing is larger than 70 nm; i.e., cell adhesion is "turned off" by RGD nanopattern order and "turned on" by the RGD nanopattern disorder if operating at this range of inter-ligand spacing.Integrin plays a central role in the formation of focal adhesions (FAs), which anchor cells to the extracellular matrix (ECM). 1 High-affinity binding of the integrin transmembrane proteins to ECM ligands has been extensively exploited for tailoring artificial synthetic ECM systems. 2 Thus far, it has been reported that cell responses to the synthetic ECM depend to a large extent on multiple substrate features, such as its chemical composition, 3-6 geometry and topographical features, 7 ligand organization, 8,9 and even substrate stiffness. 10,11 In particular, the spatial organization of the integrin-specific peptide sequence of arginineglycine-aspartic acid (RGD) on non-fouling substrates has attracted much attention. This sequence, contained in many ECM proteins, can be recognized by all five aV integrins (αVβ1, αVβ3, αVβ5, αVβ6, αVβ8), two β1 integrins (α5β1, α8β1) and αIIbβ3. 12 Once ligated, the integrin receptors link the ECM to the cytoskeleton and integrate intracellular and extracellular events. Furthermore, it is known that cellular behaviors such as adhesion, migration, proliferation and differentiation, are quite sensitive to the bioactivity, tether length, interspacing and density of surface RGD ligands in artificial ECM materials. 13-21Recent developments in nanotechnology have given access to the nanoscale organization of RGD ligands in both inorganic and polymeric substrates mimicking ECMs. Research concerning randomly dispersed RGD ligands grafted onto polymeric materials suggested that *Corresponding authors: E-mail: E-mail: Spatz@mf.mpg.de (J.P. Spatz); E-mail: jdding1@fudan.edu.cn (J. Ding). Supporting Information Available: A detailed description of the experimental protocols for sample preparation and characterization is available free of charge via the Internet at http://pubs.acs.org. Nevertheless, there has been no report to date of studies comparing cellular responses to nanostructured surfaces characterized by ordered or disordered organization of biomolecules such as RGD ligands. Herein, we chose to examine this critical issue in cell-nanomaterial interactions by exploring osteoblast adhesion regulated by the nanoscale organ...
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.
Porous scaffolds fabricated from biocompatible and biodegradable polymers play vital roles in tissue engineering and regenerative medicine. Among various scaffold matrix materials, poly(lactide-co-glycolide) (PLGA) is a very popular and an important biodegradable polyester owing to its tunable degradation rates, good mechanical properties and processibility, etc. This review highlights the progress on PLGA scaffolds. In the latest decade, some facile fabrication approaches at room temperature were put forward; more appropriate pore structures were designed and achieved; the mechanical properties were investigated both for dry and wet scaffolds; a long time biodegradation of the PLGA scaffold was observed and a three-stage model was established; even the effects of pore size and porosity on in vitro biodegradation were revealed; the PLGA scaffolds have also been implanted into animals, and some tissues have been regenerated in vivo after loading cells including stem cells.
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