Search

The construction of bioactive scaffolds with a suitable microenvironment for tissue regeneration provides a great promise for improving clinical treatment of osteochondral and full-thickness articular cartilage defects. Hydrogels of polysaccharides, such as alginate, agarose, chitosan, cellulose, hyaluronic acid, and dextran, biomimic the structure of the extracellular matrix (ECM), are exceptionally biocompatible scaffold material for tissue regeneration. The application of polysaccharide hydrogels combined with 3-dimensional (3D) printing technology can precisely distribute cell-loaded biomaterials, construct complex 3D living tissues with optimal structure and mechanical properties for osteochondral and cartilage repair. This review highlights recent advances in the development of polysaccharide-based hydrogel materials for promoting bone and cartilage tissue repair. We also highlight recent advances in 3D bioprinting polysaccharide-based hydrogel materials in cartilage regeneration. The cell type and the development of 3D bioprinting technology were described. In addition, the formation of polysaccharide – protein-based is also discussed. We outline the future trends of 3D printing including machine learning, near-infrared photopolymerization, 4D printing, and a combination of self-assembly and live-cell 3D printing-based methods.

Osteoarthritis (OA) is a challenging joint inflammatory disease that often leads to disability. Immunoregulatory Exosomes (Exos) have shown promise in OA and cartilage degeneration treatment. Engineering Exos to deliver therapeutic agents like Kartogenin (KGN) has displayed potential for restoring cartilage regeneration. However, challenges include the uneven distribution of Exos at the injury site and the release of Exos cargo out of chondrocytes. Hydrogel-loaded uMSC-Exo has demonstrated significant therapeutic effects in wound healing and tissue regeneration. Recently, a new version of three-dimensional (3D) bioprinting of hydrogel significantly restored cartilage regeneration in OA joints. Combining immune regulatory Exos with 3D bioprinting hydrogel (3D-BPH-Exos) holds the potential for immunomodulating cartilage tissue and treatment of OA. It can reduce intracellular inflammasome formation and the release of inflammatory agents like IL-1β, TNF-α, and INF-γ, while also preventing chondrocyte apoptosis by restoring mitochondrial functions and enhancing chondrogenesis in synovial MSCs, osteoprogenitor cells, and osteoclasts. Loading Exos with chondrogenic stimuli agents in the 3D-BPH-Exos approach may offer a faster and safer strategy for cartilage repair while better inhibiting joint inflammation than high doses of anti-inflammatory drugs and cell-based therapies. This review provides a comprehensive overview of hydrogel bioprinting and exosome-based therapy in OA. It emphasizes the potential of 3D-BPH-Exos loaded with chondrogenic stimuli agents for OA treatment, serving as a basis for further research.

Abstract Osteoarthritis (OA) is a common chronic disabling disease that affects hundreds of millions of people around the world. The most important pathological feature is the rupture and loss of articular cartilage, and the characteristics of avascular joint tissues lead to limited repair ability. Currently, there is no effective treatment to prevent cartilage degeneration. Studies on the mechanism of cartilage metabolism revealed that hypoxia-inducible factors (HIFs) are key regulatory genes that maintain the balance of cartilage catabolism−matrix anabolism and are considered to be the major OA regulator and promising OA treatment target. Although the exact mechanism of HIFs in OA needs to be further clarified, many drugs that directly or indirectly act on HIF signaling pathways have been confirmed by animal experiments and regarded as promising treatments for OA. Targeting HIFs will provide a promising strategy for the development of new OA drugs. This article reviews the regulation of HIFs on intra-articular cartilage homeostasis and its influence on the progression of osteoarthritis and summarizes the recent advances in OA therapies targeting the HIF system.

Abstract Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the destruction of the articular cartilage, sclerosis of the subchondral bone, and joint dysfunction. Its pathogenesis is attributed to direct damage and mechanical destruction of joint tissues. Mesenchymal stem cells (MSCs), suggested as a potential strategy for the treatment of OA, have shown therapeutic effects on OA. However, the specific fate of MSCs after intraarticular injection, including cell attachment, proliferation, differentiation, and death, is still unclear, and there is no guarantee that stem cells can be retained in the cartilage tissue to enact repair. Direct homing of MSCs is an important determinant of the efficacy of MSC-based cartilage repair. Recent studies have revealed that the unique homing capacity of MSCs and targeted modification can improve their ability to promote tissue regeneration. Here, we comprehensively review the homing effect of stem cells in joints and highlight progress toward the targeted modification of MSCs. In the future, developments of this targeting system that accelerate tissue regeneration will benefit targeted tissue repair. Graphical Abstract

Imaging of extracellular vesicles (EVs) will facilitate a better understanding of their biological functions and their potential as therapeutics and drug delivery vehicles. In order to clarify EV-mediated cellular communication in vitro and to track the bio-distribution of EV in vivo, various strategies have been developed to label and image EVs. In this review, we summarized recent advances in the tracking of EVs, demonstrating the methods for labeling and imaging of EVs, in which the labeling methods include direct and indirect labeling and the imaging modalities include fluorescent imaging, bioluminescent imaging, nuclear imaging, and nanoparticle-assisted imaging. These techniques help us better understand the mechanism of uptake, the bio-distribution, and the function of EVs. More importantly, we can evaluate the pharmacokinetic properties of EVs, which will help promote their further clinical application.

Recently, cartilage tissue engineering has become a cornerstone to treat cartilage degeneration and osteoarthritis (OA). Fibronectin1 (FN1) is described as multiple functional glycoproteins that play an essential role in chondrogenic and osteogenic differentiation. Few studies reported the potential of FN1 to enhance tissue engineering and reduce the death of chondrocytes in OA. Further, FN1 possesses multiple binding domains including collagen, integrin, and heparin that can interact with heparan sulfate proteoglycans at the surface of chondrocyte leading to promote cell signaling and differentiation. Recent studies suggested that FN1 can promote chondrocyte differentiation by upregulating TGF-β/PI3K/Akt pathways. Further, FN1 can inhibit the apoptosis of chondrocytes by preventing the release of metalloproteinases through lowering the expression of p-PI3K/PI3K and p-AKT/AKT pathways. However, the use of FN1 in cartilage repair studies using animal models or clinical trials was rarely reported. Therefore, this article provides new insights into the importance of FN1 in cartilage tissue engineering to encourage more studies concerning FN1 in cartilage repair studies. Further, we provided new suggestions for advanced applications of FN1 to treat OA and cartilage degeneration.

Wound healing and regeneration are a dynamic and complex process that requires a collaborative effort between growth factors, epidermal cells, dermal cells, extracellular matrix, and vessels local to the wound area. Mesenchymal stem cells participate in the recruitment site, mainly by releasing secretory factors and matrix proteins to promote wound healing. Stem cell-derived nanovesicles (CDNs), including microvesicles, exosomes, and exosome mimetics, contain most of the biologically active substances of their parent cells and have similar effects. CDNs can shuttle various proteins, messenger RNAs, and microRNAs to regulate the activity of receptor cells, and they play important roles in skin wound healing. This article reviews recent research progress on CDNs for wound repair. We summarize current knowledge on how CDNs regulate immunity, fibroblast activity, angiogenesis, and scar formation in the wound healing process. This review can help researchers explore new treatment strategies to enhance the therapeutic efficacy of CDNs, which have a promising future as naturally cell-free therapies.

Tissue engineering is becoming an effective strategy for repairing cartilage damage. Synthesized nanocomposite hydrogels mimic the structure of natural cartilage extracellular matrices (ECMs), are biocompatible, and exhibit nano–bio effects in response to external stimuli. These inherent characteristics make nanocomposite hydrogels promising scaffold materials for cartilage tissue engineering. This review summarizes the advances made in the field of nanocomposite hydrogels for artificial cartilage. We discuss, in detail, their preparation methods and scope of application. The challenges involved for the application of hydrogel nanocomposites for cartilage repair are also highlighted.

Three-dimensional (3D) bioprinting is an emerging technology based on 3D digital imaging technology and multi-level continuous printing. The precise positioning of biological materials, seed cells, and biological factors, known as “additive biomanufacturing”, can provide personalized therapy strategies in regenerative medicine. Over the last two decades, 3D bioprinting hydrogels have significantly advanced the field of cartilage and bone tissue engineering. This article reviews the development of 3D bioprinting and its application in cartilage tissue engineering, followed by a discussion of the current challenges and prospects for 3D bioprinting. This review presents foundational information on the future optimization of the design and manufacturing process of 3D additive biomanufacturing.

This study was conducted to investigate the effect of magnetic nanoparticle composite scaffold under a pulsed electromagnetic field on bone marrow mesenchymal stem cells (BMSCs), which was achieved by examining the biological behaviors of cell adhesion, proliferation and differentiation on the surface of the scaffolds. This may provide some experimental evidence for the use of magnetic nanoparticles in medical application. The magnetic nanoparticle composite scaffolds were evaluated and characterized by the following indexes: the cell proliferation was detected by the CCK-8 method, the alkaline phosphatase (ALP) activity was examined by a detection kit, and the expression of type I collagen and osteocalcin gene were evaluated by RT-PCR. The CCK-8 test showed that there was no significant difference in Group A (BMSCs-seeded magnetic scaffolds under the electromagnetic field), B (BMSCs-seeded magnetic scaffolds) and C (BMSCs cultured alone) (P > 0.05). The value for the ALP activity in Group A was higher than the other two groups. In addition, the RT-PCR results showed that the expression of type I collagen gene in Group A was enhanced (P 0.05). To conclude, magnetic nanoparticles may induce the osteogenic differentiation with the action of the pulsed electromagnetic field. Keywords: Magnetic nanoparticles, Bone marrow mesenchymal stem cells, Osteogenic differentiation, Pulsed electromagnetic field

A body of evidence has indicated that microRNAs (miRNAs) may have significant roles in cancer. Aberrant expression of miRNAs has frequently been observed in various human malignancies, including osteosarcoma (OS). However, the roles of miRNAs in OS remain poorly understood. In the present study, high-throughput deep sequencing was performed to screen for deregulated miRNAs in OS. Screening identified 310 miRNAs which were significantly overexpressed and 41 miRNAs which were significantly downregulated (>2-fold) in OS samples, compared with adjacent non-tumor bone tissues. Among these miRNAs, miR-33a-5p was notably downregulated. TaqMan reverse transcription- polymerase chain reaction analysis further verified that miR-33a-5p expression was significantly reduced in a large cohort of human OS samples. Enhancing miR-33a-5p expression via transfection with miR-33a-5p precursor significantly inhibited OS cell growth, suggesting potential antitumor properties of miR-33a-5p. The results of the present study provide novel insights into the miRNAs involved in OS, and suggest that miR-33a-5p may function as a tumor suppressor in OS. Therefore, miR-33a-5p may be able to serve as a diagnostic and therapeutic target for OS treatment. [ABSTRACT FROM AUTHOR]

To determine the optimal ratio of nano-hydroxyapatite (n-HA) to polylactic acid (PLLA) in the novel three-dimensional porous PLLA/n-HA composite scaffolds, low-temperature rapid prototyping technology was employed to fabricate the composite materials with different n-HA contents. Mechanical properties and degradation behaviors of the composites were examined, and the scaffold microstructure and n-HA dispersion were observed by scanning electron microscope (SEM). Mechanical tests demonstrated that the tensile strength of the composite material gradually decreased with an increase in n-HA content. When the n-HA content reached 20 wt%, the bending strength of the composite material peaked at 138.5 MPa. SEM images demonstrated that the optimal content of n-HA was 20 wt% as the largest interconnected pore size that can be seen, with a porosity as high as 80%. In vitro degradation experiments demonstrated that the pH value of the material containing solution gradually decreased in a time-dependent manner, with a simultaneous weakening of the mechanical properties. In vitro study using rat osteoblast cells showed that the composite scaffolds were biocompatible; the 20 wt% n-HA scaffold offered particular improvement to rat osteoblast cell adhesion and proliferation compared to other compositions. It was therefore concluded that 20 wt% n-HA is the optimal nano-hydroxyapatite (n-HA) to polylactic acid (PLLA) ratio, with promise for bone tissue engineering. [ABSTRACT FROM AUTHOR]

We prepared the poly-L-lactic acid (PLLA)/nanohydroxyapatite (n-HA) composite and investigated the in vitro degradation of pure PLLA material and PLLA/n-HA composites in order to identify a suitable and ideal artificial bone tissue repair material. The water uptake, weight loss, and changes in the PBS pH value and in the mechanical properties of material were measured during the processes that PLLA and PLLA/n-HA biological composites were degraded in PBS. We also performed electron microscopic scanning of the material fracture surface and observed the microscopic morphologies of materials during the degradation process. We found that the degradation rate of the PLLA/n-HA material was slower than the PLL Amaterial, and there was a little degradation of the PLLA/n-HA material at early stages. The PLLA/n-HA material also maintained the initial mechanical strength better than the pure PLLA material. The PLLA/n-HA material is thus a better material for artificial bone than the pure PLLA material. [ABSTRACT FROM AUTHOR]

Objective. To examine the biocompatibility of a novel nanohydroxyapatite/poly[lactic-co-glycolic acid] (nHA/PLGA) composite and evaluate its feasibility as a scaffold for cartilage tissue engineering. Methods. Chondrocytes of fetal rabbit were cultured with nHA/PLGA scaffold in vitro and the cell viability was assessed by MTT assay first. Cells adhering to nHA/PLGA scaffold were then observed by inverted microscope and scanning electron microscope (SEM). The cell cycle profile was analyzed by flow cytometry. Results. The viability of the chondrocytes on the scaffold was not affected by nHA/PLGA comparing with the control group as it was shown by MTT assay. Cells on the surface and in the pores of the scaffold increased in a time-dependent manner. Results obtained from flow cytometry showed that there was no significant difference in cell cycle profiles between the coculture group and control (P > 0.05). Conclusion. The porous nHA/PLGA composite scaffold is a biocompatible and good kind of scaffold for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

AbstractThe objective of this study was to assess the patterns of genotypic and phenotypic resistance in a population of blood donor patients infected with HIV-1 subtype B′ (Thai B′, a clade of HIV-1 B) from central China, previously treated and harboring NRTI and NNRTI resistance mutations, with the purpose of designing effective therapeutic regimens. The HIV-1 polgenes from 65 patients were sequenced and estimated for drug resistance while the viruses isolated from the patients were used to analyze the phenotype based on the TZM-bl cell line. All the HIV-1 strains harboring one or more drug resistance mutations to HIV-1 RTIs possessed high cross-resistance to EFV (100%) and DLV (92%), as well as to ABC (84%) and TDF (77%), which are much higher than both FTC and 3TC (42%). There were more thymidine analog mutation (TAM)-associated mutations in the AZT/ddI/NVP group (62.5%) than in the d4T/ddI/NVP group (32.65%). A phenotypic assay showed high concordance between genotypic and phenotypic cross-resistance. This study showed there was a high level of cross-drug resistance to HIV-1 RTIs among Chinese AIDS patients harboring resistant strains, and there is also a high prevalence of primary resistance to 3TC, suggesting that one important recommendation should be the realization of genotypes in all naive patients due to the high prevalence of NRTI and NNRTI mutations. [ABSTRACT FROM AUTHOR]