Fouling-resistant zwitterionic polymers for complete prevention of postoperative adhesion.

Postoperative adhesions are most common issues for almost any types of abdominal and pelvic surgery, leading to adverse consequences. Pharmacological treatments and physical barrier devices are two main approaches to address postoperative adhesions but can only alleviate or reduce adhesions to some extent. There is an urgent need for a reliable approach to completely prevent postoperative adhesions and to significantly improve the clinical outcomes, which, however, is unmet with current technologies. Here we report that by applying a viscous, cream-like yet injectable zwitterionic polymer solution to the traumatized surface, postoperative adhesion was completely and reliably prevented in three clinically relevant but increasingly challenging models in rats. The success rate of full prevention is over 93% among 42 animals tested, which is a major leap in antiadhesion performance. Clinically used Interceed film can hardly prevent the adhesion in any of these models. Unlike current antiadhesion materials serving solely as physical barriers, the "nonfouling" zwitterionic polymer functioned as a protective layer for antiadhesion applications with the inherent benefit of resisting protein/cell adhesions. The nonfouling nature of the polymer prevented the absorption of fibronectins and fibroblasts, which contribute to the initial and late-stage development of the adhesion, respectively. This is the key working mechanism that differentiated our "complete prevention" approach from current underperforming antiadhesion materials. This work implies a safe, effective, and convenient way to fully prevent postoperative adhesions suffered by current surgical patients.

Synthesis of agarose-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] zwitterionic graft copolymers via ATRP and their thermally-induced aggregation behavior in aqueous media.

A novel polysaccharide-based zwitterionic copolymer, agarose-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] (agarose-g-PDMAPS) with UCST, depending both on hydrogen bonding and electrostatic interaction, was synthesized by ATRP, and its aggregation behavior in aqueous media was investigated in detail. Proton nuclear magnetic resonance spectroscopy, Fourier transform-infrared spectroscopy, and gel-permeation chromatography were performed to characterize the copolymer. Thermosensitive behaviors of the copolymers in water, NaCl, and urea solution were tracked by ultraviolet, dynamic light scattering, and transmission electron microscopy analysis. It was found that the copolymers existed as "core-shell" spheres at an elevated temperature, as a result of the self-assembly of the agarose backbones located in the "core" driven by hydrogen-bonding interactions. When the copolymer solution was cooled below UCST, the core-shell spheres began to aggregate because of the electrostatic interactions and collapse of PDMAPS side chains in the "shell" layer. UCST of the copolymer could be tuned in a wide range, depending on the chain lengths of PDMAPS. This is the first example to investigate the thermosensitivity, combining ionic interactions of the zwitterionic side chains with hydrogen bondings from the biocompatible agarose backbones. The synthetic strategy presented here can be employed in the preparation of other novel biomaterials from a variety of polysaccharides.

Biomaterial-tight junction interaction and potential impacts.

The active pharmaceutical ingredients (APIs) have to cross the natural barriers and get into the blood to impart the pharmacological effects. The tight junctions (TJs) between the epithelial cells serve as the major selectively permeable barriers and control the paracellular transport of the majority of hydrophilic drugs, in particular, peptides and proteins. TJs perfectly balance the targeted transport and the exclusion of other unexpected pathogens under the normal conditions. Many biomaterials have shown the capability to open the TJs and improve the oral bioavailability and targeting efficacy of the APIs. Nevertheless, there is limited understanding of the biomaterial-TJ interactions. The opening of the TJs further poses the risk of autoimmune diseases and infections. This review article summarizes the most updated literature and presents insights into the TJ structure, the biomaterial-TJ interaction mechanism, the benefits and drawbacks of TJ disruption, and methods for evaluating such interactions.

Establishment of a Physical Model for Solute Diffusion in Hydrogel: Understanding the Diffusion of Proteins in Poly(sulfobetaine methacrylate) Hydrogel.

Prediction of the diffusion coefficient of solute, especially bioactive molecules, in hydrogel is significant in the biomedical field. Considering the randomness of solute movement in a hydrogel network, a physical diffusion RMP-1 model based on obstruction theory was established in this study. The physical properties of the solute and the polymer chain and their interactions were introduced into this model. Furthermore, models RMP-2 and RMP-3 were established to understand and predict the diffusion behaviors of proteins in hydrogel. In addition, zwitterionic poly(sulfobetaine methacrylate) (PSBMA) hydrogels with wide range and fine adjustable mesh sizes were prepared and used as efficient experimental platforms for model validation. The Flory characteristic ratios, Flory-Huggins parameter, mesh size, and polymer chain radii of PSBMA hydrogels were determined. The diffusion coefficients of the proteins (bovine serum albumin, immunoglobulin G, and lysozyme) in PSBMA hydrogels were studied by the fluorescence recovery after photobleaching technique. The measured diffusion coefficients were compared with the predictions of obstruction models, and it was found that our model presented an excellent predictive ability. Furthermore, the assessment of our model revealed that protein diffusion in PSBMA hydrogel would be affected by the physical properties of the protein and the PSBMA network. It was also confirmed that the diffusion behaviors of protein in zwitterionic hydrogels can be adjusted by changing the cross-linking density of the hydrogel and the ionic strength of the swelling medium. Our model is expected to possess accurate predictive ability for the diffusion coefficient of solute in hydrogel, which will be widely used in the biomedical field.

Electrospun PDLLA/PLGA composite membranes for potential application in guided tissue regeneration.

With the aim to explore a membrane system with appropriate degradation rate and excellent cell-occlusiveness for guided tissue regeneration (GTR), a series of poly(D, L-lactic acid) (PDLLA)/poly(D, L-lactic-co-glycolic acid) (PLGA) (100/0, 70/30, 50/50, 30/70, 0/100, w/w) composite membranes were fabricated via electrospinning. The fabricated membranes were evaluated by morphological characterization, water contact angle measurement and tensile test. In vitro degradation was characterized in terms of the weight loss and the morphological change. Moreover, in vitro cytologic research revealed that PDLLA/PLGA composite membranes could efficiently inhibit the infiltration of 293 T cells. Finally, subcutaneous implant test on SD rat in vivo showed that PDLLA/PLGA (70/30, 50/50) composite membranes could function well as a physical barrier to prevent cellular infiltration within 13 weeks. These results suggested that electrospun PDLLA/PLGA (50/50) composite membranes could serve as a promising barrier membrane for guided tissue regeneration due to suitable biodegradability, preferable mechanical properties and excellent cellular shielding effects.