Enhanced hyaline cartilage formation and continuous osteochondral regeneration via 3D-Printed heterogeneous hydrogel with multi-crosslinking inks.

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.

Type II collagen scaffolds repair critical-sized osteochondral defects under induced conditions of osteoarthritis in rat knee joints via inhibiting TGF-ß-Smad1/5/8 signaling pathway.

The bidirectional relationship between osteochondral defects (OCD) and osteoarthritis (OA), with each condition exacerbating the other, makes OCD regeneration in the presence of OA challenging. Type II collagen (Col2) is important in OCD regeneration and the management of OA, but its potential applications in cartilage tissue engineering are significantly limited. This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration. Furthermore, the repair potential of Col2 scaffolds was validated in over critical-sized OCD models. After 90 days or 150 days since scaffold implantation, complete healing was observed histologically in critical-sized OCD, evidenced by the excellent integration with surrounding native tissues. The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties. The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue. Additionally, transcriptome and proteome analysis revealed the hindrance of TGF-ß-Smad1/5/8 in regenerated OA tissue. In conclusion, the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-ß-Smad1/5/8 signaling pathway.

Fabrication and Performance Evaluation of Gelatin/Sodium Alginate Hydrogel-Based Macrophage and MSC Cell-Encapsulated Paracrine System with Potential Application in Wound Healing.

A gelatin/sodium alginate-based hydrogel microsphere has been fabricated after reaction condition optimization. Macrophages (RAW246.7) and adipose mesenchymal stem cells (ADSC) have been subsequently encapsulated in the microsphere in order to construct a 3D paracrine system for wound healing treatment. The synthesized microsphere displayed neglectable cytotoxicity toward both encapsulated cells until 10 days of incubation, indicating promising biocompatibility of the microsphere. A qRT-PCR and ELISA experiment revealed positive regulation of cytokines (Arg-1, IL-6, IL-8, IL-10, bFGF, HGF, VEGF, TLR-1, and CXCL13) expression regarding macrophage phenotype transformation and anti-inflammatory performance both inside the microsphere and in the microenvironment of established in vitro inflammatory model. Additionally, positive tendency of cytokine expression benefit wound healing was more pronounced in a fabricated 3D paracrine system than that of a 2D paracrine system. Furthermore, the 3D paracrine system exhibited more efficiently in the wound healing rate compared to the 2D paracrine system in an in vitro model. These results suggested the current paracrine system could be potentially used as a robust wound healing dressing.

An Instant Underwater Tissue Adhesive Composed of Catechin-Chondroitin Sulfate and Cholesterol-Polyethyleneimine.

Due to the safety issue and poor underwater adhesion of current commercially available bioadhesives, they are hard to apply to in vivo physiological environments and more diverse medical use conditions. In this study, a novel and facile bioadhesive for underwater medical applications are designed based on the coacervation of electrostatic interactions and hydrophobic interactions, with the introduction of catechin as a provider of catechol moieties for adhesion to surrounding tissues. The orange-colored bio-adhesive, named PcC, is generated within seconds by mixing catechin-modified chondroitin sulfate and cholesterol chloroformate-modified polyethyleneimine with agitation. In vitro mechanical measurements prove that this novel PcC bio-adhesive is superior in underwater adhesion performance when applied to cartilage. Animal experiments in a rat mastectomy model and rat cartilage graft implantation model demonstrate its potential for diverse medical purposes, such as closing surgical incisions, reducing the formation of seroma, and tissue adhesive applied in orthopedic or cartilage surgery.

Design strategies for adhesive hydrogels with natural antibacterial agents as wound dressings: Status and trends.

The wound healing process is usually susceptible to different bacterial infections due to the complex physiological environment, which significantly impairs wound healing. The topical application of antibiotics is not desirable for wound healing because the excessive use of antibiotics might cause bacteria to develop resistance and even the production of super bacteria, posing significant harm to human well-being. Wound dressings based on adhesive, biocompatible, and multi-functional hydrogels with natural antibacterial agents have been widely recognized as effective wound treatments. Hydrogels, which are three-dimensional (3D) polymer networks cross-linked through physical interactions or covalent bonds, are promising for topical antibacterial applications because of their excellent adhesion, antibacterial properties, and biocompatibility. To further improve the healing performance of hydrogels, various modification methods have been developed with superior biocompatibility, antibacterial activity, mechanical properties, and wound repair capabilities. This review summarizes hundreds of typical studies on various ingredients, preparation methods, antibacterial mechanisms, and internal antibacterial factors to understand adhesive hydrogels with natural antibacterial agents for wound dressings. Additionally, we provide prospects for adhesive and antibacterial hydrogels in biomedical applications and clinical research.

Superlarge living hyaline cartilage graft contributed by the scale-changed porous 3D culture system for joint defect repair.

It is known that an excellent hyaline cartilage phenotype, an internal microstructure with safe crosslinking and available size flexibility are the key factors of cartilage grafts that allow for clinical application. Living hyaline cartilage grafts (LhCGs) constructed by phase-transfer hydrogel (PTCC) systems were reported to have a hyaline phenotype and bionic microstructure. By employing chondrocytes to secrete matrix in the hydrogel and then removing the material to obtain material-free tissuein vitro, LhCG technology exhibited superior performance in cartilage repair. However, PTCC systems could only produce small-sized LhCGs because of medium delivery limitations, which hinders the clinical application of LhCGs. In this study, we prepared three different noncrosslinked gelatin microspheres with diameters from 200 µm to 500 µm, which replaced the original pore-forming agent. The new PTCC system with the mixed and gradient porous structure was used for the preparation of superlarge LhCGs with a continuous structure and hyaline phenotype. Compared to the original technique, the porous gradient structure promoted nutrient delivery and cartilage matrix secretion. The small size of the microporous structure promoted the rapid formation of matrix junctions. The experimental group with a mixed gradient increased cartilage matrix secretion significantly by more than 50% compared to the that of the control. The LhCG final area reached 7 cm2without obvious matrix stratification in the mixed gradient group. The design of the scale-changed porous PTCC system will make LhCGs more promising for clinical application.

Engineering strategies to achieve efficient in vitro expansion of haematopoietic stem cells: development and improvement.

Haematopoietic stem cells are the basis for building and maintaining lifelong haematopoietic mechanisms and an important resource for the treatment of blood disorders. Haematopoietic niches are a microenvironment in the body where stem cells tend to accumulate, with some nurse cells protecting and regulating stem cells. On the basis of biology, materials science, and engineering, researchers have constructed stem cell niches to address the current clinical shortage of stem cells and to explore stem cell behaviour for biomedical research. Herein, three main resource categories involved in haematopoietic stem cell niche engineering are reviewed: first, the basic approach to construct bionic cell culture environments is to use cytokines, nurse cells or extracellular matrix; second, microscale technologies are applied to mimic the properties of natural stem cell niches; and finally, biomaterials are used to construct the three-dimensional extracellular matrix-like culture environment.

Steady Enhancement in Photovoltaic Properties of Fluorine Functionalized Quinoxaline-Based Narrow Bandgap Polymer.

To investigate the influence of fluoride phenyl side-chains onto a quinoxaline (Qx) unit on the photovoltaic performance of the narrow bandgap (NBG) photovoltaic polymers, herein, two novel NBG copolymers, PBDTT-DTQx and PBDTT-DTmFQx, were synthesized and characterized. 2-ethylhexylthiothiophene-substituted benzodithiophene (BDTT), 2,3-diphenylquinoxaline (DQx) [or 2,3-bis(3-fluorophenyl)quinoxaline (DmFQx)] and 2-ethylhexylthiophene (T) were used as the electron donor (D) unit, electron-withdrawing acceptor (A) unit and π-bridge, respectively. Compared to non-fluorine substituted PBDTT-DTQx, fluoride PBDTT-DTmFQx exhibited a wide UV-Vis absorption spectrum and high hole mobility. An enhanced short-circuit current (Jsc) and fill factor (FF) simultaneously gave rise to favorable efficiencies in the polymer/PC71BM-based polymer solar cells (PSCs). Under the illumination of AM 1.5G (100 mW cm-2), a maximum power conversion efficiency (PCE) of 6.40% was achieved with an open-circuit voltage (Voc) of 0.87 V, a Jsc of 12.0 mA cm-2 and a FF of 61.45% in PBDTT-DTmFQx/PC71BM-based PSCs, while PBDTT-DTQx-based devices also exhibited a PCE of 5.43%. The excellent results obtained demonstrate that PBDTT-DTmFQx by fluorine atom engineering could be a promising candidate for organic photovoltaics.

[Advances in traditional Chinese medicine treatment of schistosomiasis liver fibrosis].

Recent years, three is a lot of literature in traditional Chinese medicine treatment of schistosomiasis liver fibrosis, and the clinical experiences are very rich. This paper reviews the data of pathogenesis, diagnosis and treatment, and basic prescriptions of traditional Chinese medicine for schistosomiasis liver fibrosis, and proposes the individual treatment ideas.

Facile Synthesis of Mono-Dispersed Polystyrene (PS)/Ag Composite Microspheres via Modified Chemical Reduction.

A modified method based on in situ chemical reduction was developed to prepare mono-dispersed polystyrene/silver (PS/Ag) composite microspheres. In this approach; mono-dispersed PS microspheres were synthesized through dispersion polymerization using poly-vinylpyrrolidone (PVP) as a dispersant at first. Then, poly-dopamine (PDA) was fabricated to functionally modify the surfaces of PS microspheres. With the addition of [Ag(NH3)2]⁺ to the PS dispersion, [Ag(NH3)2]⁺ complex ions were absorbed and reduced to silver nanoparticles on the surfaces of PS-PDA microspheres to form PS/Ag composite microspheres. PVP acted both as a solvent of the metallic precursor and as a reducing agent. PDA also acted both as a chemical protocol to immobilize the silver nanoparticles at the PS surface and as a reducing agent. Therefore, no additional reducing agents were needed. The resulting composite microspheres were characterized by TEM, field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), XRD, UV-Vis and surface-enhanced Raman spectroscopy (SERS). The results showed that Ag nanoparticles (NPs) were homogeneously immobilized onto the PS microspheres' surface in the presence of PDA and PVP. PS/Ag composite microspheres were well formed with a uniform and compact shell layer and were adjustable in terms of their optical property.

Size-tunable near-infrared PbS nanoparticles synthesized from lead carboxylate and sulfur with oleylamine as stabilizer.

High quality PbS nanocrystals are synthesized reproducibly through lead stearate and sulfur stabilized by oleylamine in a non-coordinating solvent. The morphology, crystalline form and phase composition of PbS nanocrystals are examined by transmission electron microscopy (TEM), high-resolution TEM, x-ray diffraction (XRD), energy-dispersive x-ray spectroscopy (EDS) and x-ray photoelectron spectroscopy (XPS). The as-synthesized PbS nanocrystals have strong absorption and photoluminescence emissions in the near-infrared region. The size of PbS nanocrystals from 5 to 13 nm can be adjusted through the optimization of the synthesis conditions. The smaller PbS nanoparticles are obtained at the lower reaction temperature, lower precursor concentration, larger oleylamine quantity and larger lead precursor/sulfur ratio. The basic oleylamine enhances the reactivity of both lead stearate precursor and sulfur precursor in the reaction.