Injectable Thermogel Generated by the "Block Blend" Strategy as a Biomaterial for Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection is an established method for the removal of early cancers and large lesions from the gastrointestinal tract but is faced with the risk of perforation. To decrease this risk, a submucosal fluid cushion (SFC) is needed clinically by submucosal injection of saline and so on to lift and separate the lesion from the muscular layer. Some materials have been tried as the SFC so far with disadvantages. Here, we proposed a thermogel generated by the "block blend" strategy as an SFC. This system was composed of two amphiphilic block copolymers in water, so it was called a "block blend". We synthesized two non-thermogellable copolymers poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) and blended them in water to achieve a sol-gel transition upon heating in both pure water and physiological saline. We explored the internal structure of the resultant thermogel with transmission electron microscopy, three-dimensional light scattering, 13C NMR, fluorescence resonance energy transfer, and rheological measurements, which indicated a percolated micelle network. The biosafety of the synthesized copolymer was preliminarily confirmed in vitro. The main necessary functions as an SFC, namely, injectability of a sol and the maintained mucosal elevation as a gel after injection, were verified ex vivo. This study has revealed the internal structure of the block blend thermogel and illustrated its potential application as a biomaterial. This work might be stimulating for investigations and applications of intelligent materials with both injectability and thermogellability of tunable phase-transition temperatures.

Cell migration regulated by RGD nanospacing and enhanced under moderate cell adhesion on biomaterials.

While nanoscale modification of a biomaterial surface is known to influence various cell behaviors, it is unclear whether there is an optimal nanospacing of a bioactive ligand with respect to cell migration. Herein, we investigated the effects of nanospacing of arginine-glycine-aspartate (RGD) peptide on cell migration and its relation to cell adhesion. To this end, we prepared RGD nanopatterns with varied nanospacings (31-125 nm) against the nonfouling background of poly(ethylene glycol), and employed human umbilical vein endothelial cells (HUVECs) to examine cell behaviors on the nanopatterned surfaces. While HUVECs adhered well on surfaces of RGD nanospacing less than 70 nm and exhibited a monotonic decrease of adhesion with the increase of RGD nanospacing, cell migration exhibited a nonmonotonic change with the ligand nanospacing: the maximum migration velocity was observed around 90 nm of nanospacing, and slow or very slow migration occurred in the cases of small or large RGD nanospacings. Therefore, moderate cell adhesion is beneficial for fast cell migration. Further molecular biology studies revealed that attenuated cell adhesion and activated dynamic actin rearrangement accounted for the promotion of cell migration, and the genes of small G proteins such as Cdc42 were upregulated correspondingly. The present study sheds new light on cell migration and its relation to cell adhesion, and paves a way for designing biomaterials for applications in regenerative medicine.

Structural mechanics of 3D-printed poly(lactic acid) scaffolds with tetragonal, hexagonal and wheel-like designs.

While various porous scaffolds have been developed, the focused study about which structure leads to better mechanics is rare. In this study, we designed porous scaffolds with tetragonal, hexagonal and wheel-like structures under a given porosity, and fabricated corresponding poly(lactic acid) (PLA) scaffolds with three-dimensional printing. High-resolution micro-computed tomography was carried out to calculate their experimental porosity and confirm their high interconnectivity. The theoretical and experimental compressive properties in the longitudinal direction were characterized by finite element analysis method and electromechanical universal testing system, respectively. Thereinto, the scaffold with the tetragonal structure exhibited higher mechanical strength both theoretically and experimentally. Creep and stress relaxation behaviors of the scaffolds revealed that the tetragonal scaffold had less significant viscoelasticity. Immersion dynamic mechanical analysis was performed to test their cycle-loading fatigue behaviors in the simulated body fluid at 37 °C; the tetragonal scaffold exhibited the latest fatigue beginning point at 4400 cycles, which indicated a better anti-fatigue performance; the hexagonal and wheel-like ones exhibited the middle and earliest fatigue beginning points at 3200 and 2500 cycles, respectively. What is more, cytocompatibility and histocompatibility of the scaffolds with all of the structures were confirmed by cell counting kit-8 assay in vitro and three-month subcutaneous implantation in rats in vivo. Hence, the key property difference of the three examined structures comes from their mechanics; the tetragonal structure exhibited better mechanics in the longitudinal direction examined in this study, which could be taken into consideration in design of a porous scaffold for tissue engineering and regeneration.

Strategy of Metal-Polymer Composite Stent To Accelerate Biodegradation of Iron-Based Biomaterials.

The new principle and technique to tune biodegradation rates of biomaterials is one of the keys to the development of regenerative medicine and next-generation biomaterials. Biodegradable stents are new-generation medical devices applied in percutaneous coronary intervention, etc. Recently, both corrodible metals and degradable polymers have drawn much attention in biodegradable stents or scaffolds. It is, however, a dilemma to achieve good mechanical properties and appropriate degradation profiles. Herein, we put forward a metal-polymer composite strategy to achieve both. Iron stents exhibit excellent mechanical properties but low corrosion rate in vivo. We hypothesized that coating of biodegradable aliphatic polyester could accelerate iron corrosion due to the acidic degradation products, etc. To demonstrate the feasibility of this composite material technique, we first conducted in vitro experiments to affirm that iron sheet corroded faster when covered by polylactide (PLA) coating. Then, we fabricated three-dimensional metal-polymer stents (MPS) and implanted the novel stents in the abdominal aorta of New Zealand white rabbits, setting metal-based stents (MBS) as a control. A series of in vivo experiments were performed, including measurements of residual mass and radial strength of the stents, histological analysis, micro-computed tomography, and optical coherence tomography imaging at the implantation site. The results showed that MPS could totally corrode in some cases, whereas iron struts of MBS in all cases remained several months after implantation. Corrosion rates of MPS could be easily regulated by adjusting the composition of PLA coatings.

Achieving High Drug Loading and Sustained Release of Hydrophobic Drugs in Hydrogels through In Situ Crystallization.

Inadequate drug loading of hydrophobic drugs is a classic problem when hydrogels are utilized as sustained-release carriers of drugs. Herein, a strategy to load plenty of hydrophobic drugs is presented. The antitumor drug 10-hydroxycamptothecin in the thermogel of poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) is employed. The drug is soluble in an alkaline medium, yet insoluble in a neutral/acidic medium. The crystallization is triggered after adding an alkaline drug solution into an acidic copolymer solution. The concentrated copolymer aqueous solution undergoes a sol-gel transition upon heating, faster than the crystallization. As a result, plenty of evenly dispersed drug microcrystals are formed. The in vitro and in vivo experiments indicate both high drug loading and sustained release with enhanced antitumor efficacy and reduced adverse effects. The system resolves the challenge in formulation of hydrophobic drugs in hydrogels, and is stimulating for encapsulating drugs with a soluble-insoluble transition into a material environment.