Development of watertight and bioabsorbable synthetic dural substitutes

Abstract:  We have developed novel watertight and bioabsorbable synthetic dural substitutes. The substitutes were designed such that they had a three-layered structure, and each layer comprised a bioabsorbable copolymer prepared from l -lactide, glycolide, and ε-caprolactone. Various copolymers were synthesized, and appropriate compositions were selected for preparing the substitutes based on the results of leakage tests. Experimental substitutes that prevented the leakage of saline through the suture lines between the substitutes and dura mater were prepared. An in vitro study was performed in which the substitutes were sutured to porcine dura mater, and the amount of saline leakage was measured. It was demonstrated that leakage through the suture line could be completely suppressed by using the substitutes we developed along with favorable suturing techniques.     

Dendronized Hyperbranched Polyethyleneimines with Switchable Thermoresponsiveness and Encapsulation

Hyperbranched polyethyleneimines (PEIs) with multiple layered structures and high density of terminal amino groups have shown great potential for applications in biomedicine, sensors, and catalysis. In this work, a kind of dendronized hyperbranched PEIs (DHPs) is synthesized by modification of PEIs with dendritic oligoethylene glycols (OEGs). These DHPs not only inherit the characteristic thermoresponsive behavior from the OEG dendrons, but also show low cytotoxicity and switchable encapsulation capacities. Their thermoresponsive behavior is found to be mainly dependent on the coverage and amphiphilicity of dendritic OEGs, solution pH, and NaCl concentration. Moreover, DHPs exhibit advantages in thermally-switchable complexation with guest molecules because of their adjustable crowding effect from the densely packed OEG chains. In addition, these DHPs can also be used as nanoreactors, which can reduce metal ions into metal nanoparticles in a convenient way. In virtue of these peculiarities, it is believed that these dendronized hyperbranched PEIs with smart properties can be used as promising scaffolds in drug-controlled release and nanoreactors.     

Bacterial biopolymers: From production to applications in biomedicine

Bacterial polymers obtained tremendous attention over the decades owing to its widespread use in biomedical applications. A better understanding on metabolic pathways and development of improved production strategies through metabolic engineering tools to synthesize tailor made polymer materials to meet their applicability in biomedicine. This review focuses on wide range of these biocompatible polymeric materials include polysaccharides, polyesters, polyamides and polyphosphates with wound healing, antioxidant, antitumor, antimicrobial activities. This review focuses on the advantages of various biomaterials to obtain controlled/sustained drug release and tissue engineering applications in biomedical field and the applications of microbial polysaccharides as drugs in pharmaceutical industry. This review describes the most prominent biomedical applications of bacterial biopolymer material as wound healing bandages, drug delivery, tissue engineering, ortho-dental applications and hydrogels. Reviews the future aspects based on economic feasibility and challenges in mass production and downstream processing of biopolymers and its tailor made synthesis to accomplish diverse applications.     

Substituent-Controlled Energetics and Barriers of Mechanochromic Spiropyran-Functionalized Poly(ɛ-caprolactone)

In a joint theoretical and experimental study, it is shown that the onset of the mechanically-induced spiropyran (SP) to merocyanine (MC) isomerization can be controlled by both the regiochemistry and the substitution pattern of SP. Four SP-based bifunctional initiators with consistently varied polymer chain anchor point and substituent are used to synthesize poly-ε-caprolactone (PCL). Theoretical calculations (1S and 3S COGEF methods) and in-situ visible light absorption measurements of films during uniaxial stress–strain experiments consistently show varying activation barriers of the force-induced ring-opening reaction of SP to give MC. SPs with PCL chains attached in ortho-position to the pyran oxygen isomerize at lower stress than their para-analogs. NO₂-substituted SP mechanophores exhibit a lower activation barrier compared with H-substituted ones, but only if the  NO₂ substituent is located in para-position relative to the O at the pyran half. These results are consistent with theoretical loading rate-dependent rupture forces required to break the C O bond of SP and may guide mechanophore design.     

Catalyst-Free Multicomponent Tandem Polymerizations of Aliphatic Amines,Activated Alkyne,and Formaldehyde toward Poly(tetrahydropyrimidine)s

Poly(tetrahydropyrimidine)s are promising heterocyclic polymers with unique biocompatibility, antibacterial ability, inherent fluorescence property, and so on, whose development is limited by their synthetic approaches. Multicomponent polymerizations (MCPs) are a group of powerful tools for the facile construction of heterocyclic polymers from simple monomers. Herein, a catalyst-free multicomponent tandem polymerization of aliphatic diamines, activated alkyne, and formaldehyde was developed at 60 °C in methanol in air to construct poly(tetrahydropyrimidine)s with well-defined structures, high molecular weights (M_w up to 57700 g mol⁻¹), high yields (up to 84%), and satisfactory thermal stability. The MCP was featured with commercially available monomers, high efficiency, catalyst-free economic and mild condition, which was applicable to aliphatic diamines with complicated chemical reactivity, providing a robust and efficient approach for the synthesis of diversified heterocyclic polymers such as poly(tetrahydropyrimidine)s.     

Emerging Concepts in Iodine Transfer Polymerization

Controlled radical polymerization corresponds to variety of synthetic strategies that aim the generation of precise macromolecular architectures. Iodine transfer polymerization (ITP) is one of the oldest methods to conduct controlled radical polymerization; however, it seems to have lost visibility compared to other popular techniques. It relies on utilization of iodine species in reversible deactivation kinetics, and it has some significant advantages compared to other methods. Its simplicity, minimized toxicity, metal-free nature, no coloring on final product, and ease of purification provide widespread applicability, even in industry. In this perspective, the basics of ITP are re-introduced, and emerging technologies (heterophase polymerization, photoinitiation, and sustainability) in ITP are discussed.     

A Polymer Lost in the Shuffle: The Perspective of Poly(para)phenylenes

During 1990s, poly(para)phenylenes (PPPs) are one of the most prominent and hyped classes of conjugated polymers. Even though they have been heavily investigated for different applications, they are now eking out a rather niche existence. It is believed that this decline of interest partly has come from the early obstacle of synthesizing high-molecular weight, processable, and defect-free PPPs. Early examples of PPPs are not only rather oligomers than polymers but also contain many regiochemical and structural defects. Furthermore, early unsubstituted materials are infusible and insoluble, which have made their practical application almost impossible. Another reason for the decline of research interest in PPPs may be their underperformance in early applications, particularly in organic light-emitting diodes (OLEDs), which ultimately lead to a lack of follow-up publications. However, over the last two decades not only more precise and advanced synthesis methods have arisen but also a more profound understanding of those applications has been achieved within which new technological approaches have emerged. It is believed that PPPs would benefit from this development. Accordingly, in this perspective, the synthesis, structures, properties, and applications of PPPs reported so far as well as their potential in future technologies are discussed.     

Marangoni-Driven Patterning in Polymer Thin Film Supported on Shrinking Substrate for Resolution Enhancement

The Marangoni effect causes liquids to flow toward localized regions with higher surface tension. In a polymer thin film, the flow induced by photochemically programmed surface tension gradients can be harnessed to manufacture patterned surfaces. Patterned polymer films are particularly useful for controlling adhesion, improving photonic device efficiency, and directing cellular alignment. In general, a broader range of accessible pattern resolutions and/or aspect ratios ensures a broader range of applications. However, because of the process flow for pattern formation, the final pattern periodicity of the Marangoni-driven features matches that of the initially prescribed surface energy pattern. To achieve better resolution without using sophisticated and complex tools, a shrinking (or pre-strained) polymer film is used as a substrate. The shrinking substrate can “contract or densify” the features along the substrate plane. Consequently, the resolution of the patterns formed on the shrinking substrate is improved by the shrinkage rate of the substrate compared with those formed on the non-shrinking substrate (i.e., silicon wafer).     

Side Chain Engineering of Amphiphilic Conjugated Polymer Nanoparticles for Biofilm Ablation

Biofilm recalcitrance, which enables bacteria to survive deep within the body under antimicrobial treatment, leading to persistent infections by reducing the penetration of antimicrobials, remains a major challenge in the antibacterial field. Conjugated polymer-based nanoparticles with near-infrared (NIR) photo responsiveness have emerged as a promising class of photothermal agents for biofilm ablation. However, the development of CPNs has been limited due to dissociation of the nanoparticles synthesized through nanoprecipitation. In this study, surface-functionalized amphiphilic conjugated polymer-based nanoparticles with photothermal conversion capacity for pH-responsive targeting of bacteria are developed. The pH-sensitive properties of the nanoparticles promote their adhesion to negatively charged bacterial surfaces, resulting in accumulation in biofilms. This accumulation enhances the ablation efficiency of biofilms under the synergistic photothermal effect. The method of constructing functional amphiphilic conjugated polymer-based nanoparticles is simple to operate and can be used universally, providing a potential design option for biocompatible light-responsive nanoparticles for in vivo applications.