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 ...

Ningbo University

A commentary on "Enhanced recovery after low- and medium-risk liver transplantation. A single-center prospective observational cohort study".

Microbial infection, caused by fungi, bacteria, viruses, and parasites, significantly contributes to the global death burden and health costs. The innate and adaptive immune systems orchestrate a multifaceted signaling response to invading pathogens as the human antimicrobial system. In this process, caspase recruitment domain-containing protein 9 (CARD9) emerges as a critical intermediary adaptor molecule to participate in regulating a series of antimicrobial immune reactions. Previous publications have confirmed that CARD9 plays a crucial role in fungal, bacterial, viral, and parasitic infections. In this study, we aim to provide an update on the recent clinical and basic studies where the mechanism and function of CARD9 have been further studied and understood. In addition, we summarize the latest treatment and prevention strategies based on CARD9 and discuss the current perspectives and future direction of CARD9.

CARD9 in host immunity to fungal, bacterial, viral, and parasitic infections: An update.

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.

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.

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.

Zeming Hu

Health Science Center

Ningbo University

Embedded Bioprinting of Tissue-like Structures Using κ-Carrageenan Sub-Microgel Medium

Zeming Hu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Health Science Center

Ningbo University

Embedded Bioprinting of Tissue-like Structures Using κ-Carrageenan Sub-Microgel Medium

Health Science Center