Decorating Delivery Vehicles Using Hyaluronic Acid Oligosaccharides Enables Active Targeting Toward Cancer and Minimizes Adverse Effect of Chemotherapeutics.

The major drawback of conventional chemotherapeutic treatment is the non-specificity or inability to ascertain and target cancerous cells directly. In this study, an active targeting strategy that is poised to carry the anticancer agents to the desired sites for therapeutic action while avoiding toxicity to normal organs is provided. The active targeting of delivery vehicles is achieved by ligand-receptor interactions, in particular the specific binding between hyaluronic acid oligosaccharides (oHAs) and CD44 receptors.

Sulfated hyaluronic acid/collagen-based biomimetic hybrid nanofiber skin for diabetic wound healing: Development and preliminary evaluation.

Diabetic foot ulcers (DFUs) are one of the most serious and devastating complication of diabetes, manifesting as foot ulcers and impaired wound healing in patients with diabetes mellitus. To solve this problem, sulfated hyaluronic acid (SHA)/collagen-based nanofibrous biomimetic skins was developed and used to promote the diabetic wound healing and skin remodeling. First, SHA was successfully synthetized using chemical sulfation and incorporated into collagen (COL) matrix for preparing the SHA/COL hybrid nanofiber skins.

Construction of enzyme-laden vascular scaffolds based on hyaluronic acid oligosaccharides-modified collagen nanofibers for antithrombosis and in-situ endothelialization of tissue-engineered blood vessels.

The current use of synthetic grafts often yields low patency in the reconstruction of small-diameter blood vessels owing to the deposition of thrombi and imperfect coverage of the endothelium on the graft lumen. Therefore, the design of vascular scaffolds with antithrombotic performance and endothelialization is greatly required. Herein, we developed an enzyme-laden scaffold based on hyaluronic acid oligosaccharides-modified collagen nanofibers (labeled HA-COL) to improve the anti-platelet capacity and endothelialization of vascular grafts.

New injectable chitosan-hyaluronic acid based hydrogels for hemostasis and wound healing.

It is a challenge to develop hemostatic and wound dressings that are used for irregular shape and deep wound. Herein, a series of novel N-succinyl chitosan-oxidized hyaluronic acid based (NSC-OHA-based) hydrogels were fabricated, while calcium ions (Ca) and/or four-armed amine-terminated poly(ethylene glycol) (4-arm-PEG-NH, labeled as PEG1) were introduced to regulate the mechanical behavior and bioactivities. We found all NSC-OHA-based hydrogels displayed self-healing and injectable performances.

Biochemical Characterization and Synthetic Application of WciN and Its Mutants From Serotype 6B.

The biochemical properties of α-1,3-galactosyltransferase WciN from serotype 6B were systemically characterized with the chemically synthesized Glcα-PP-(CH)-OPh as an acceptor substrate. The site-directed mutation of D38 and A150 residues of WciN was further investigated, and the enzymatic activities of those WciN mutants revealed that A150 residue was the pivotal residue responsible for nucleotide donor recognition and the single-site mutation could completely cause pneumococcus serotype switch. Using WciN and WciN mutants as useful tool enzymes, the disaccharides Galα1,3Glcα-PP-(CH)-OPh and Glcα1,3Glcα-PP-(CH)-OPh were successfully prepared in multi-milligram scale in high yields.

Hyaluronic acid oligosaccharide-collagen mineralized product and aligned nanofibers with enhanced vascularization properties in bone tissue engineering.

Considering the structural complexity of natural bone and the limitations of current treatment options, designing a biomimetic and functional tissue-engineered bone graft has been an urgent need for the replacement and regeneration of defected bone tissue. In light of the cell recruitment to the defect region, scaffold-guided bone tissue engineering has proven to be a viable strategy that is poised to deliver effective osseointegration and vascularization during bone remodeling. Herein, we provide an engineered bone scaffold based on aligned poly(lactic-co-glycolide) (PLGA) nanofibers incorporated with hyaluronic acid oligosaccharide-collagen mineralized microparticles (labeled oHA-Col/HAP) to guide the cell-specific orientation and osseointegration in bone healing.

Hyaluronic acid oligosaccharides modified mineralized collagen and chitosan with enhanced osteoinductive properties for bone tissue engineering.

In this study, we prepared a biomimetic hyaluronic acid oligosaccharides (oHAs)-based composite scaffold to develop a bone tissue-engineered scaffold for stimulating osteogenesis and endothelialization. The functional oHAs products were firstly synthesized, namely collagen/hyaluronic acid oligosaccharides/hydroxyapatite (Col/oHAs/HAP), chitosan/hyaluronic acid oligosaccharides (CTS/oHAs), and then uniformly distributed in poly (lactic-co-glycolic acid) (PLGA) solution followed by freeze-drying to obtain three-dimensional interconnected scaffolds as temporary templates for bone regeneration. The morphology, physicochemical properties, compressive strength, and degradation behavior of the fabricated scaffolds, as well as in vitro cell responses seeded on these scaffolds and in vivo biocompatibility, were investigated to evaluate the potential for bone tissue engineering.

Fabrication and assessment of chondroitin sulfate-modified collagen nanofibers for small-diameter vascular tissue engineering applications.

Chondroitin sulfate (ChS) has shown promising results in promoting cell proliferation and antithrombogenic activity. To engineered develop a dual-function vascular scaffold with antithrombosis and endothelialization, ChS was tethered to collagen to accelerate the growth of endothelial cells and prevent platelet activation. First, ChS was used to conjugate with collagen to generate glycosylated products (ChS-COL) via reductive amination.

Exploring the broad nucleotide triphosphate and sugar-1-phosphate specificity of thymidylyltransferase Cps23FL from serotype 23F.

Glucose-1-phosphate thymidylyltransferase (Cps23FL) from serotype 23F is the initial enzyme that catalyses the thymidylyl transfer reaction in prokaryotic deoxythymidine diphosphate-l-rhamnose (dTDP-Rha) biosynthetic pathway. In this study, the broad substrate specificity of Cps23FL towards six glucose-1-phosphates and nine nucleoside triphosphates as substrates was systematically explored, eventually providing access to nineteen sugar nucleotide analogs.

Design and comprehensive assessment of a biomimetic tri-layer tubular scaffold via biodegradable polymers for vascular tissue engineering applications.

Considering the structural complexity of the native artery wall and the limitations of current treatment strategies, developing a biomimetic tri-layer tissue-engineered vascular graft is a major developmental direction of vascular tissue regeneration. Biodegradable polymers exhibit adequate mechanical characteristics and feasible operability, showing potential prospects in the construction of tissue engineering scaffold. Herein, we present a bio-inspired tri-layer tubular graft using biodegradable polymers to simulate natural vascular architecture.

Improving in vitro biocompatibility on biomimetic mineralized collagen bone materials modified with hyaluronic acid oligosaccharide.

Hyaluronic acid (HA) has great potential in bone tissue engineering due to its favorable bioactivity and biocompatibility, especially hyaluronic acid oligosaccharides (oHAs) shows a promising result in endothelialization of blood vessel. To improve endothelialized effect and osteogenic performance of bone scaffold, we have created a biomimetic nanofiber network based on collagen modified with hyaluronic acid oligosaccharides (Col/oHAs) and its mineralized product. Biomimetically mineralized Col/oHAs based composite (Col/oHAs/HAP) was prepared via self-assembly at room temperature.

Hyaluronic acid oligosaccharide-modified collagen nanofibers as vascular tissue-engineered scaffold for promoting endothelial cell proliferation.

Hyaluronic acid oligosaccharides (oHAs) have shown promising results in promoting vascular endothelial cell (EC) proliferation and endothelialization. To engineered develop tissue scaffold for promoting EC proliferation and vessel endothelialization, different sizes of oHAs were prepared and grafted onto collagen to improve the biological properties of the synthesized materials, especially in angiogenesis. Firstly, oHAs were successfully prepared and conjugated with collagen to construct glycosylated collagens by reductive amination.

Biochemical studies of a β-1,4-rhamnoslytransferase from Streptococcus pneumonia serotype 23F.

A new β-rhamnoslytransferase Cps23FT from Streptococcus pneumonia serotype 23F was expressed and characterized. Its enzymatic activity and function were confirmed for the first time by utilizing enzymatically prepared dTDP-Rha and chemically synthesized Glcα-PP-(CH2)11-OPh as substrates. This reaction gave the desired disaccharide Rhaβ-1,4-Glcα-PP-(CH2)11-OPh in a good isolated yield (67%), suggesting the potential of Cps23FT as a tool enzyme for the synthesis of complex oligosaccharides containing difficult β-rhamnosyl linkages.

Mechanical enhancement and in vitro biocompatibility of nanofibrous collagen-chitosan scaffolds for tissue engineering.

The collagen-chitosan complex with a three-dimensional nanofiber structure was fabricated to mimic native ECM for tissue repair and biomedical applications. Though the three-dimensional hierarchical fibrous structures of collagen-chitosan composites could provide more adequate stimulus to facilitate cell adhesion, migrate and proliferation, and thus have the potential as tissue engineering scaffolding, there are still limitations in their applications due to the insufficient mechanical properties of natural materials. Because poly (vinyl alcohol) (PVA) and thermoplastic polyurethane (TPU) as biocompatible synthetic polymers can offer excellent mechanical properties, they were introduced into the collagen-chitosan composites to fabricate the mixed collagen/chitosan/PVA fibers and a sandwich structure (collagen/chitosan-TPU-collagen/chitosan) of nanofiber in order to enhance the mechanical properties of the nanofibrous collagen-chitosan scaffold.

One-pot four-enzyme synthesis of thymidinediphosphate-l-rhamnose.

A new, robust one-pot four-enzyme synthetic method was developed for thymidinediphosphate-l-rhamnose starting from d-glucose-1-phosphate. The enzymes, Glc-1-P thymidylyltransferase, dTDP-Glc-4,6-dehydratase, dTDP-4-keto-6-deoxy-Glc-3,5-epimerase and dTDP-4-keto-Rha reductase were derived from Streptococcus pneumonia serotype 23F, expressed in Escherichia coli, and studied in detail to provide the first direct evidence for their functions.

Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration.

The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability.

Improved workability of injectable calcium sulfate bone cement by regulation of self-setting properties.

Calcium sulfate hemihydrate (CSH) powder as an injectable bone cement was prepared by hydrothermal synthesis of calcium sulfate dihydrate (CSD). The prepared materials showed X-ray diffraction peaks corresponding to the CSH structure without any secondary phases, implying complete conversion from CSD phase to CSH phase. Thermogravimetric (TG) analyses showed the crystal water content of CSH was about 6.

Mechanical properties and in vitro bioactivity of injectable and self-setting calcium sulfate/nano-HA/collagen bone graft substitute.

Calcium sulfate hemihydrate (CSH) was introduced into the mineralized collagen (nHAC) to prepare an injectable and self-setting in situ bone graft substitute. The mechanical properties of materials, which are dependant on the L/S ratio, the content of nHAC and setting accelerator, were discussed based on the satisfying injectability and setting properties. It was found that the compressive strength and modulus of materials increased with the decrease of nHAC content and L/S ratio.

Injectable calcium sulfate/mineralized collagen-based bone repair materials with regulable self-setting properties.

An injectable and self-setting bone repair materials (nano-hydroxyapatite/collagen/calcium sulfate hemihydrate, nHAC/CSH) was developed in this study. The nano-hydroxyapatite/collagen (nHAC) composite, which is the mineralized fibril by self-assembly of nano-hydrocyapatite and collagen, has the same features as natural bone in both main hierarchical microstructure and composition. It is a bioactive osteoconductor due to its high level of biocompatibility and appropriate degradation rate.

Injectable bone cement based on mineralized collagen.

A novel injectable bone cement based on mineralized collagen was reported in this paper. The cement was fabricated by introducing calcium sulfate hemihydrate (CaSO(4).1/2H(2)O, CSH) into nano-hydroxyapatite/collagen (nHAC).