embedded-bioprinting-tissue-like-structures-using-carrageenan-sub

Embedded Bioprinting of Tissue-like Structures Using &#954;-Carrageenan Sub-Microgel Medium

Embedded three-dimensional (3D) bioprinting utilizing a granular hydrogel supporting bath has emerged as a critical technique for creating biomimetic ...

The synthesis of thiophene C-nucleoside analogues bearing sugar residues (mono- and disaccharides) and aromatic residues has been achieved by symmetric dimerization of terminal sugar alkynes or unsymmetric dimerization of terminal sugar alkynes and substituted iodoethynylbenzene followed by sulfur heterocyclization in one pot. Homocoupling of terminal sugar alkynes and subsequent sulfur heterocyclization produce thiophene C-nucleoside analogues bearing disaccharides. Unsymmetric dimerization of terminal sugar alkynes and substituted iodoethynylbenzene followed by sulfur heterocyclization give thiophene C-nucleoside analogues bearing monosaccharide and aromatic residues. This approach is concise, general and mild, and is suitable for structurally diverse pyranosides, furanosides, and acyclic sugars. Thirty-two examples have been given and the corresponding products are obtained in moderate to excellent yields.

Concise synthesis of thiophene C-nucleoside analogues bearing sugar residues and aromatic residues through dimerization and sulfur heterocyclization of sugar alkynes and substituted iodoethynylbenzene.

Nanotechnology using biodegradable polymer carriers with good biocompatibility and bioabsorbability has been studied and applied extensively in drug delivery systems and biomedical engineering. In this work, the triblocked oligomer poly(L-lactide)--poly(ethylene glycol)--poly(L-lactide) (PLEL) with the molecular weight of 2.08 KDa was first synthesized. Its chemistry was characterized by hydrogen nuclear magnetic resonance (H-NMR) spectrum and Fourier transform infrared (FTIR) spectroscopy. Subsequently, the nanoparticles (NPs) of PLEL and pranoprofen (PF)-loaded PLEL were prepared with the average particle size of (151.7 ± 5.87) nm using the method of emulsion solvent evaporation. The formula and drug releasing profile were characterized by a transmission electron microscope (TEM), dynamic light scattering (DLS), and ultraviolet spectrophotometer (US).  cytotoxicity assays and  ophthalmic tests were performed to measure the safety and efficacy of the formulations. The results showed that PF NPs relieved the cytotoxicity of pure PF and eliminated ophthalmic irritation. The drug encapsulated in the nanoparticles displayed long-lasting release and good anti-inflammation efficiency in animal eyes. Therefore, we concluded that the present formula (PF NPs) could provide sustained drug release with good treatment effect on eye inflammation, and is promising for its use in ophthalmology in the future.

Pranoprofen Nanoparticles With (L-)-b-()-(L-) as the Matrix Toward Improving Ocular Anti-inflammation.

Medical device contamination caused by microbial pathogens such as bacteria and fungi has posed a severe threat to the patients' health in hospitals. Due to the increasing resistance of pathogens to antibiotics, the efficacy of traditional antibiotics treatment is gradually decreasing for the infection treatment. Therefore, it is urgent to develop new antibacterial drugs to meet clinical or civilian needs. Antibacterial polymers have attracted the interests of researchers due to their unique bactericidal mechanism and excellent antibacterial effect. This article reviews the mechanism and advantages of antimicrobial polymers and the consideration for their translation. Their applications and advances in medical device surface coating were also reviewed. The information will provide a valuable reference to design and develop antibacterial devices that are resistant to pathogenic infections.

The Mechanisms and the Applications of Antibacterial Polymers in Surface Modification on Medical Devices.

Skin wounds not only cause physical pain for patients but also are an economic burden for society. It is necessary to seek out an efficient approach to promote skin repair. Hydrogels are considered effective wound dressings. They possess many unique properties like biocompatibility, biodegradability, high water uptake and retention etc., so that they are promising candidate materials for wound healing. Chitosan is a polymeric biomaterial obtained by the deacetylation of chitin. With the properties of easy acquisition, antibacterial and hemostatic activity, and the ability to promote skin regeneration, hydrogel-like functional wound dressings (represented by chitosan and its derivatives) have received extensive attentions for their effectiveness and mechanisms in promoting skin wound repair. In this review, we extensively discussed the mechanisms with which chitosan-based functional materials promote hemostasis, anti-inflammation, proliferation of granulation in wound repair. We also provided the latest information about the applications of such materials in wound treatment. In addition, we summarized the methods to enhance the advantages and maintain the intrinsic nature of chitosan via incorporating other chemical components, active biomolecules and other substances into the hydrogels.

Chitosan-Based Functional Materials for Skin Wound Repair: Mechanisms and Applications.

A series of hydrogels containing guanidine-based polymers using a poloxamer as the matrix were prepared to provide novel wound dressings with antibacterial and repairing-promotion properties for skin wounds. Herein, we developed a series of antibacterial hydrogels, the cationic guanidine-based polymer polyhexamethylene guanidine hydrochloride (PHMG) with poloxamer aqueous solution (12%, w/w) simplified as PHMGP, chitosan (CS)-cross-linked PHMG (referred to as PHMC) with poloxamer aqueous solution simplified as PHMCP, and hyaluronic acid (HA)-modified PHMG (referred to as PHMH) with poloxamer aqueous solution simplified as PHMHP, for enhancing full-thickness skin wound healing. The characterizations, antimicrobial activity, cytotoxicity, and in vivo full-thickness wound-healing capability of these hydrogels were analyzed and evaluated. The results show that though PHMGP possesses great bactericide properties, its cytotoxicity is too strong to support skin regeneration. However, after modified with CS or HA, PHMCP and PHMHP showed good biocompatibility and antimicrobial properties against Gram-positive and Gram-negative bacteria that are commonly present in injured skin. Both PHMCP and PHMHP hydrogels exhibited upgraded wound-healing efficiency in full-thickness skin defects, characterized by a shorter wound closure time, faster re-regeneration, and the earlier formation of skin appendages, compared with those of control or pure poloxamer treatments. Their biological mechanism was detected. Both PHMCP and PHMHP can regulate the related biofactors during the skin repair process such as interleukin-1β (IL-1β), interleukin-6 (IL-6), transforming growth factor beta-1(TGF-β1), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor, to promote wound healing with less serious scarring. In short, hydrogels with excellent capabilities to inhibit microorganism infection and promote wound healing were developed, which will shed light on designing and producing wound dressings with promising applications in future.

Development of Poloxamer Hydrogels Containing Antibacterial Guanidine-Based Polymers for Healing of Full-Thickness Skin Wound.

Amniotic membrane (AM) transplantation is often used as a treatment for corneal repair, but AM is prone to dissolving and shedding after surgery; multiple transplants will cause pain and financial burden. In this work, human amniotic membrane was firstly decellularized to obtain an AM extracellular matrix (dAM). This dAM was homogenized and extracted to obtain the dAM extract (simplified as dAME). Different forms of administration for corneal injury were performed as liquid drops (diluted dAME),  gels (using temperature-dependent Poloxamer 407 as the matrix), and tablets (poly(vinyl alcohol) as the matrix). The cytocompatibility of dAME was evaluated using corneal epithelial cells, corneal stromal cells and fibroblasts as cell models. The results showed that dAME is biocompatible to all these cells. Cells exhibited normal morphology and growth state at a dAME concentration of up to 160 μg mL. , dAME exhibited increased wound healing efficiency in severe corneal injury, being characterized with a shorter healing time for epithelium and a faster recovery for stromal opacity and thickness, compared with those of the control eyes. Different forms of administration have different effects on corneal repair; among them,  gels achieved the best therapeutic efficiency. Their biological mechanism was detected  quantitative real-time polymerase chain reaction (qRT-PCR) technology. It was confirmed that dAME plays important roles in promoting the mRNA expression of leucine-rich and immunoglobulin-like domains 1 (LRIG1) and in inhibiting the mRNA of transforming growth factor-β1 (TGF-β1).

Various administration forms of decellularized amniotic membrane extract towards improving corneal repair.

Myopia, also known as nearsightedness, is one of the prime reasons for vision impairment worldwide. Atropine in topical ophthalmic solutions (e.g., 0.01% atropine sulfate eye drops) is the primary medical treatment for controlling myopia, especially for pseudomyopia or true myopia in rapid progress. However, aqueous atropine solution is unstable and easily breaks down to tropic acid, which will result in vision blur. Drug-eluting contact lenses (CLs) have been explored as a potentially superior alternative to effectively control the drug release and improve the drug efficacy. In this work, an atropine-eluting contact lens was developed by encapsulating an atropine implant in a silicon-based contact lens, towards functioning in vision correction and controlling myopia. The safety and effectiveness of this atropine-eluting contact lens were verified with rabbit and guinea pig models. The results showed that the lenses reduced the side effects like mydriasis and no other adverse events were observed in rabbit eyes. More importantly, atropine-loaded lenses could effectively delay the progress of form-deprivation myopia with guinea pig eyes as the model. Thus, we concluded that atropine-eluting CLs prepared by implantation technology may be an option for the treatment of myopia.

Atropine-eluting silicone contact lenses for myopia control.

Pro-inflammatory and anti-inflammatory types are the main phenotypes of the macrophage, which are commonly notified as M1 and M2, respectively. The alteration of macrophage phenotypes and the progression of inflammation are intimately associated; both phenotypes usually coexist throughout the whole inflammation stage, involving the transduction of intracellular signals and the secretion of extracellular cytokines. This paper aims to address the interaction of macrophages and surrounding cells and tissues with inflammation-related diseases and clarify the crosstalk of signal pathways relevant to the phenotypic metamorphosis of macrophages. On these bases, some novel therapeutic methods are proposed for regulating inflammation through monitoring the transition of macrophage phenotypes so as to prevent the negative effects of antibiotic drugs utilized in the long term in the clinic. This information will be quite beneficial for the diagnosis and treatment of inflammation-related diseases like pneumonia and other disorders involving macrophages.

Biologic Mechanisms of Macrophage Phenotypes Responding to Infection and the Novel Therapies to Moderate Inflammation.

Surface-enhanced Raman scattering (SERS) has great potential in the field of rapid detection of pesticide residues in food. In this paper, a fiber optic SERS sensor excited by evanescent waves was proposed for efficient detection of thiram. Silver nanocubes (Ag NCs) were prepared as SERS active substrates, which had much stronger electromagnetic field intensity than nanospheres under laser excitation due to much more "hot spots". By using the method of electrostatic adsorption and laser induction, Ag NCs were uniformly assembled at the fiber taper waist (FTW) for enhancing the Raman signal. Different from the traditional way of stimulation, evanescent wave excitation greatly increased the interaction area between the excitation and analyte, while reducing the damage of the excited light to the metal nanostructures. The methods proposed in this work have been successfully used to detect the pesticide residues of thiram and showed good detection performance. The detection limits for 4-Mercaptobenzoic acid (4-MBA) and thiram were determined to be 10 and 10 M, the corresponding enhancement factor could be 1.64 × 10 and 6.38 × 10. Low concentration of thiram was detected in the peels of tomatoes and cucumbers, indicating its feasibility in actual sample detection. The combination of evanescent waves and SERS provides a new direction for the application of SERS sensors, which had great application potential in the field of pesticide residue detection.

Fiber Optic SERS Sensor with Silver Nanocubes Attached Based on Evanescent Wave for Detecting Pesticide Residues.

The treatment of gastric ulcer and perforation using synthetic and biomaterials has been a clinical challenge. In this work, a drug-carrying layer of hyaluronic acid was combined with a gastric submucosal decellularized extracellular matrix called gHECM. The regulation of macrophage polarization by the extracellular matrix's components was then investigated. This work proclaims how gHECM responds to inflammation and aids in the regeneration of the gastric lining by altering the phenotype of surrounding macrophages and stimulating the body's whole immune response. In a nutshell, gHECM promotes tissue regeneration by changing the phenotype of macrophages around the site of injury. In particular, gHECM reduces the production of pro-inflammatory cytokines, decreases the percentage of M1 macrophages, and further encourages differentiation of macrophage subpopulation to the M2 phenotype and the release of anti-inflammatory cytokines, which could block the NF-κB pathway. Activated macrophages are capable of immediately delivering through spatial barriers, modulating the peripheral immune system, influencing the inflammatory microenvironment, and ultimately promoting the recovery of inflammation and healing of ulcers. They contribute to the secreted cytokines that act on local tissues or enhance the chemotactic ability of macrophages through paracrine secretion. In this study, we focused on the immunological regulatory network of macrophage polarization to further develop the mechanisms behind this process. Nevertheless, the signaling pathways involved in this process need to be further explored and identified. We think that our research will encourage more investigation into how the decellularized matrix affects immune modulation and will help the decellularized matrix perform better as a new class of natural biomaterials for tissue engineering.

Repairing gastric ulcer with hyaluronic acid/extracellular matrix composite through promoting M2-type polarization of macrophages.

The human amniotic membrane (hAM) is the innermost layer of the placenta. Its distinctive structure and the biological and physical characteristics make it a highly biocompatible material in a variety of regenerative medicine applications. It also acts as a supply of bioactive factors and cells, which indicate the advantages over other tissues. In this review, we firstly discussed the biological properties of hAM-derived cells , along with their stemness of markers, pointing out a promising source of stem cells for regenerative medicine. Then, we systematically summarized current knowledge on the collection, preparation, preservation, and decellularization of hAM, as well as their characteristics helping to improve the understanding of applications in tissue engineering. Finally, we highlighted the recent advances in which hAM has undergone additional modifications to achieve an adequate perspective of regenerative medicine applications. More investigations are required in utilizing appropriate modifications to enhance the therapeutic effectiveness of hAM in the future.

Biological importance of human amniotic membrane in tissue engineering and regenerative medicine.

Engineered scaffolds are used for repairing damaged esophagus to allow the precise alignment and movement of smooth muscle for peristalsis. However, most of these scaffolds focus solely on inducing cell alignment through directional apparatus, often overlooking the promotion of muscle tissue formation and causing reduced esophageal muscle repair effectiveness. To address this issue, we first introduced aligned nano-ferroferric oxide (FeO) assemblies on a micropatterned poly(ethylene glycol) (PEG) hydrogel to form micro-/nano-stripes. Further modification using a gold coating was found to enhance cellular adhesion, orientation and organization within these micro-/nano-stripes, which consequently prevented excessive adhesion of smooth muscle cells (SMCs) to the thin PEG ridges, thereby effectively confining the cells to the FeO-laid channels. This architectural design promotes the alignment of the cytoskeleton and elongation of actin filaments, leading to the organized formation of muscle bundles and a tendency for SMCs to adopt synthetic phenotypes. Muscle patches are harvested from the micro-/nano-stripes and transplanted into a rat esophageal defect model.  experiments demonstrate the exceptional viability of these muscle patches and their ability to accelerate the regeneration of esophageal tissue. Overall, this study presents an efficient strategy for constructing muscle patches with directional alignment and muscle bundle formation of SMCs, holding significant promise for muscle tissue regeneration.

Engineered muscle from micro-channeled PEG scaffold with magnetic FeO fixation towards accelerating esophageal muscle repair.

FOXD1, a new member of the  transcription factor family, serves as a mediator and biomarker for cell reprogramming. But its contribution to prognosis of uveal melanoma (UVM) is unclear. This study demonstrated that  might promote tumor growth and invasion, because  expression was negatively correlated with overall survival, progression-free survival, and disease-specific survival in UVM patients. This conjecture was verified in cell culture with human uveal melanoma cell line (MUM2B) as model cells. Additionally, the biological mechanisms of  based on -related genomic spectrum, molecular pathways, tumor microenvironment, and drug treatment sensitivity were examined using The Cancer Genome Atlas (TCGA) database, aiming to reasonably explain why  leads to poor prognosis of UVM. On these bases, a novel tumor prognostic model was established using the -related immunomodulators , , , and , which will enable the stratification of disease seriousness and clinical treatment for patients.

 expression-based prognostic model for uveal melanoma.

Three-dimensional (3D) bioprinting embedded within a microgel bath has emerged as a promising strategy for creating intricate biomimetic scaffolds. However, it remains a great challenge to construct tissue-scale structures with high resolution by using embedded 3D bioprinting due to the large particle size and polydispersity of the microgel medium, as well as its limited cytocompatibility. To address these issues, novel uniform sub-microgels of cell-friendly cationic-crosslinked kappa-carrageenan (-Car) are developed through an easy-to-operate mechanical grinding strategy. These-Car sub-microgels maintain a uniform submicron size of around 642 nm and display a rapid jamming-unjamming transition within 5 s, along with excellent shear-thinning and self-healing properties, which are critical for the high resolution and fidelity in the construction of tissue architecture via embedded 3D bioprinting. Utilizing this new sub-microgel medium, various intricate 3D tissue and organ structures, including the heart, lungs, trachea, branched vasculature, kidney, auricle, nose, and liver, are successfully fabricated with delicate fine structures and high shape fidelity. Moreover, the bone marrow mesenchymal stem cells encapsulated within the printed constructs exhibit remarkable viability exceeding 92.1% and robust growth. This-Car sub-microgel medium offers an innovative avenue for achieving high-quality embedded bioprinting, facilitating the fabrication of functional biological constructs with biomimetic structural organizations.

Cation-crosslinked-carrageenan sub-microgel medium for high-quality embedded bioprinting.

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

Article	Year
Concise synthesis of thiophene C-nucleoside analogues bearing sugar residues and aromatic residues through dimerization and sulfur heterocyclization of sugar alkynes and substituted iodoethy... Organic & biomolecular chemistry\| PubMed ID: 32080693	2020
Pranoprofen Nanoparticles With (L-)-b-()-(L-) as the Matrix Toward Improving Ocular Anti-inflammation. Frontiers in bioengineering and biotechnology\| PubMed ID: 33224933	2020
The Mechanisms and the Applications of Antibacterial Polymers in Surface Modification on Medical Devices. Frontiers in bioengineering and biotechnology\| PubMed ID: 33262975	2020
Chitosan-Based Functional Materials for Skin Wound Repair: Mechanisms and Applications. Frontiers in bioengineering and biotechnology\| PubMed ID: 33681176	2021
Development of Poloxamer Hydrogels Containing Antibacterial Guanidine-Based Polymers for Healing of Full-Thickness Skin Wound. ACS biomaterials science & engineering\| PubMed ID: 34423628	2021
Various administration forms of decellularized amniotic membrane extract towards improving corneal repair. Journal of materials chemistry. B\| PubMed ID: 34724021	2021
Atropine-eluting silicone contact lenses for myopia control. Journal of biomaterials applications\| PubMed ID: 37083186	2023
Biologic Mechanisms of Macrophage Phenotypes Responding to Infection and the Novel Therapies to Moderate Inflammation. International journal of molecular sciences\| PubMed ID: 37176064	2023
Fiber Optic SERS Sensor with Silver Nanocubes Attached Based on Evanescent Wave for Detecting Pesticide Residues. ACS applied materials & interfaces\| PubMed ID: 37327489	2023
Repairing gastric ulcer with hyaluronic acid/extracellular matrix composite through promoting M2-type polarization of macrophages. International journal of biological macromolecules\| PubMed ID: 37364804	2023
Biological importance of human amniotic membrane in tissue engineering and regenerative medicine. Materials today. Bio\| PubMed ID: 37711653	2023
Engineered muscle from micro-channeled PEG scaffold with magnetic FeO fixation towards accelerating esophageal muscle repair. Materials today. Bio\| PubMed ID: 38024845	2023
expression-based prognostic model for uveal melanoma. Heliyon\| PubMed ID: 38027647	2023
Cation-crosslinked-carrageenan sub-microgel medium for high-quality embedded bioprinting. Biofabrication\| PubMed ID: 38198708	2024
Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration. Journal of materials chemistry. B\| PubMed ID: 38700242	2024

Yang Luo

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