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Introduction: Osteochondral repair poses a significant challenge due to its unique pathological mechanisms and complex repair processes, particularly in bacterial tissue conditions resulting from open injuries, infections, and surgical contamination. This study introduces a biomimetic honeycomb-like scaffold (Zn-AlgMA@Mg) designed for osteochondral repair. The scaffold consists of a dicalcium phosphate dihydrate (DCPD)-coated porous magnesium scaffold (DCPD Mg) embedded within a dual crosslinked sodium alginate hydrogel (Zn-AlgMA). This combination aims to synergistically exert antibacterial and osteochondral integrated repair properties.Methods: The Zn-AlgMA@Mg scaffold was fabricated by coating porous magnesium scaffolds with DCPD and embedding them within a dual crosslinked sodium alginate hydrogel. The structural and mechanical properties of the DCPD Mg scaffold were characterized using scanning electron microscopy (SEM) and mechanical testing. The microstructural features and hydrophilicity of Zn-AlgMA were assessed. In vitro studies were conducted to evaluate the controlled release of magnesium and zinc ions, as well as the scaffold’s osteogenic, chondrogenic, and antibacterial properties. Proteomic analysis was performed to elucidate the mechanism of osteochondral integrated repair. In vivo efficacy was evaluated using a rabbit full-thickness osteochondral defect model, with micro-CT evaluation, quantitative analysis, and histological staining (hematoxylin-eosin, Safranin-O, and Masson’s trichrome).Results: The DCPD Mg scaffold exhibited a uniform porous structure and superior mechanical properties. The Zn-AlgMA hydrogel displayed consistent microstructural features and enhanced hydrophilicity. The Zn-AlgMA@Mg scaffold provided controlled release of magnesium and zinc ions, promoting cell proliferation and vitality. In vitro studies demonstrated significant osteogenic and chondrogenic properties, as well as antibacterial efficacy. Proteomic analysis revealed the underlying mechanism of osteochondral integrated repair facilitated by the scaffold. Micro-CT evaluation and histological analysis confirmed successful osteochondral integration in the rabbit model.Discussion: The biomimetic honeycomb-like scaffold (Zn-AlgMA@Mg) demonstrated promising results for osteochondral repair, effectively addressing the challenges posed by bacterial tissue conditions. The scaffold’s ability to release magnesium and zinc ions in a controlled manner contributed to its significant osteogenic, chondrogenic, and antibacterial properties. Proteomic analysis provided insights into the scaffold’s mechanism of action, supporting its potential for integrated osteochondral regeneration. The successful in vivo results highlight the scaffold’s efficacy, making it a promising biomaterial for future applications in osteochondral repair.

Short peptides have become the focus of recent research due to their variable bioactivities, good digestibility and wide existences in food-derived protein hydrolysates. However, due to the high complexity of the samples, identifying short peptides still remains a challenge. In this work, a tool, named PeposX-Exhaust, was developed for short peptide identification. Through validation with known peptides, PeposX-Exhaust identified all the submitted spectra and the accuracy rate reached 75.36%, and the adjusted accuracy rate further reached 98.55% when with top 5 candidates considered. Compared with other tools, the accuracy rate by PeposX-Exhaust was at least 70% higher than two database-search tools and 15% higher than the other two de novo-sequencing tools, respectively. For further application, the numbers of short peptides identified from soybean, walnut, collagen and bonito protein hydrolysates reached 1145, 628, 746 and 681, respectively. This fully demonstrated the superiority of the tool in short peptide identification.

Brucellosis is a zoonotic infectious disease that has long endangered the development of animal husbandry and human health. Currently, vaccination stands as the most efficacious method for preventing and managing brucellosis. Alum, as the most commonly used adjuvant for the brucellosis vaccine, has obvious disadvantages, such as the formation of granulomas and its non-degradability. Therefore, the aims of this study were to prepare an absorbable, injectable, and biocompatible hydroxypropyl chitin (HPCT) thermosensitive hydrogel and to evaluate its immunization efficacy as an adjuvant for Brucella antigens. Specifically, etherification modification of marine natural polysaccharide chitin was carried out to obtain a hydroxypropyl chitin. Rheological studies demonstrated the reversible temperature sensitivity of HPCT hydrogel. Notably, 5 mg/mL of bovine serum albumin can be loaded in HPCT hydrogels and released continuously for more than one week. Furthermore, the L929 cytotoxicity test and in vivo degradation test in rats proved that an HPCT hydrogel had good cytocompatibility and histocompatibility and can be degraded and absorbed in vivo. In mouse functional experiments, as adjuvants for Brucella antigens, an HPCT hydrogel showed better specific antibody expression levels and cytokine (Interleukin-4, Interferon-γ) expression levels than alum. Thus, we believe that HPCT hydrogels hold much promise in the development of adjuvants.

It is still a major challenge to remove tumor cells and fill bone defects after tumor resection. Combined with the 3D printing technology, the composite bioceramics scaffolds were fabricated with interconnected porous magnesium-doped wollastonite (CSi-Mg) scaffolds as the architecture and nano-hydroxyapatite (n-HA) as the surface. The influence of manufacturing process on the n-HA layer thickness and degradation performance, biological performance and anti-tumor performance of the composite scaffolds were investigated. The n-HA surface layer could effectively retard the degradation rate of CSi-Mg scaffolds and maintain high mechanical strength (over 90 MPa) after immersion in simulated body fluid for 3 weeks. Meanwhile, CSi-Mg/n-HA3 scaffold induced about 50 % of cell death for human osteosarcoma cells (MG-63) in vitro. CSi-Mg/n-HAx (x = 1, 3) scaffolds could improve the osteogenic performance of Rat BMSC. These findings demonstrate that the bioceramic composite scaffold with high strength, good osteogenic performance and anti-tumor performance is promising for the treatment of tissue injury after resection of osteosarcoma.

Abstract Background Osteosarcoma (OS) is a malignant tumor originating from mesenchymal stem cells, and has an extremely high fatality rate and ability to metastasize. Although mounting evidence suggests that miR-769-5p is strongly associated with the malignant progression and poor prognosis of various tumors, the exact role of miR-769-5p in OS is still unclear. Therefore, this study aimed to explore the relationship between miR-769-5p and the malignant progression of OS, and its underlying mechanism of action. Methods miR-769-5p expression was analyzed in GSE28423 from the GEO database and measured in OS clinical specimens and cell lines. The effects of miR-769-5p on OS proliferation, migration and invasion were measured both in vivo and in vitro. In addition, bioinformatics analyses and luciferase reporter assays were used to explore the target genes of miR-769-5p. Rescue experiments were also conducted. Moreover, a co-culture model was used to test the cell interaction between bone mesenchymal stem cells (BMSC) and OS cells. Results We found that miR-769-5p is highly expressed in OS clinical specimens and cell lines. In vivo and in vitro experiments also showed that miR-769-5p significantly promoted the proliferation, migration and invasion of OS cells. Dual-specific phosphatase 16 (DUSP16) was negatively associated with miR-769-5p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiments showed that DUSP16 reverses the effect of miR-769-5p on OS cells by negatively regulating the JNK/p38 MAPK signaling pathway. Additionally, the results of the co-culture of BMSCs and OS cells confirmed that miR-769-5p was transferred from BMSCs to OS cells through exosomes. Conclusions In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS.

Bone defects, a common orthopedic problem in clinical practice, are a serious threat to human health. As alternative materials to autologous bone grafts, synthetic cell-free functionalized scaffolds have been the focus of recent research in designing scaffolds for bone tissue engineering. Butyryl chitin (BC) is a derivative of chitin (CT) with improved solubility. It has good biocompatibility, but few studies have investigated its use in bone repair. In this study, BC was successfully synthesized with a degree of substitution of 2.1. BC films were prepared using the cast film method and showed strong tensile strength (47.8 ± 4.54 N) and hydrophobicity (86.4 ± 2.46°), which was favorable for mineral deposition. An in vitro cytological assay confirmed the excellent cell attachment and cytocompatibility of the BC film; meanwhile, in vivo degradation indicated the good biocompatibility of BC. Hydroxyapatite (HA), extracted from bovine cancellous bone, had good cytocompatibility and osteogenic induction activity for the mouse osteoblast cell line MC3T3-E1. With the aim of combining the advantages of BC and HA, a BC–HA composite scaffold, with a good pore structure and mechanical strength, was prepared by physical mixing. Administered into skull defects of rats, the scaffolds showed perfect bone-binding performance and effective structural support, and significantly promoted the regeneration of new bone. These results prove that the BC–HA porous scaffold is a successful bone tissue engineering scaffold and has strong potential to be further developed as a substitute for bone transplantation.

Increasing evidence indicates that lymphocyte cytosolic protein 1 (LCP1) overexpression contributes to tumor progression; however, its role in osteosarcoma (OS) remains unclear. We aimed to investigate the potential effect of LCP1 in OS and the underlying mechanisms. We first demonstrated that LCP1 is upregulated in OS cell lines and tissues. Then, we found that aberrant expression of LCP1 could induce the proliferation and metastasis of OS cells in vitro and in vivo by destabilizing neuregulin receptor degradation protein-1 (Nrdp1) and subsequently activating the JAK2/STAT3 signaling pathway. When coculturing OS cells with bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, we validated that oncogenic LCP1 in OS was transferred from BMSCs via exosomes. Moreover, microRNA (miR)-135a-5p, a tumor suppressor, was found to interact upstream of LCP1 to counteract the pro-tumorigenesis effects of LCP1 in OS. In conclusion, BMSC-derived exosomal LCP1 promotes OS proliferation and metastasis via the JAK2/STAT3 pathway. Targeting the miR-135a-5p/LCP1 axis may have potential in treating OS.

Chitosan (CTS) has been used as a nerve guidance conduit (NGC) material for bridging peripheral nerve defects due to its biocompatible, biodegradable, and non-toxic properties. However, the nerve regeneration effect of chitosan alone is restricted due to its inadequate biological activity. Herein, a composite, bioactive chitosan based nerve conduit, consisting of outer warp-knitted tube scaffold made from medical-grade chitosan fiber, and inner porous cross linked carboxymethyl chitosan (C-CM-CTS) sponge with radial texture was developed. The inner wall of the scaffold was coated with C-CM-CTS solution. CM-CTS provided favorable bioactivities in the composite chitosan-based nerve conduit. An in vitro study of CM-CTS revealed its satisfying biocompatibility with fibroblast and its inhibition of oxidative damage to Schwann cells. As the internal filler of the NGC, the lyophilized sponge of C-CM-CTS showed a longitudinal guidance effect for nerve reconstruction. After 10 mm defect in rat sciatic nerve was bridged with the composite bioactive chitosan-based nerve conduit, the nerve conduit was able to effectively promote axonal regeneration and played a positive role in inducing nerve regeneration and functional recovery. In addition to the functional advantages, which are equal to those of an autograft; the technology for the preparation of this conduit can be put into mass production.

Accumulating evidence has indicated that abnormal microRNAs (miRNAs) serve critical roles in carcinogenesis and development of osteosarcoma (OS). The purpose of the present study was to elucidate the relationship between miR-766-3p and development of osteosarcoma and explore the potential mechanism. In this study, we found that miR-766-3p was the most downregulated miRNA by analyzing GSE65071 from the GEO database. miR-766-3p was lowly expressed in OS tissue samples and cells, and high miR-766-3p expression repressed the malignant level of OS, including cell proliferation, EMT, migration, and invasion in vitro and in vivo. B-Cell Lymphoma 9-Like Protein (BCL9L) was negatively associated with miR-766-3p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiment indicated that BCL9L could restore the influence of miR-766-3p on OS cells. In addition, the β-Catenin/TCF-4 signal pathway was demonstrated to be related to the miR-766-3p/BCL9L axis. In summary, miR-766-3p, a negative regulator of BCL9L, plays the role of tumor metastasis suppressor via the β-catenin signaling pathway in the progression of OS.

Cancer is considered to have an adverse influence on health around the world. Chitosan, a linear polysaccharide that contains copolymers of β-1-4 linked d-glucosamine and N-acetyl-d-glucosamine units, has been widely used in the field of biomedicine, owing to its nontoxicity, biocompatibility, biodegradability, and hemocompatibility. This study was aimed at preparing the chitosan oligosaccharides (COS) and examining its ability on suppressing lung cancer in vitro and in vivo. Human non-small-cell lung cancer A549 cells model and C57BL/6 mice bearing lung cancer model were adopted. COS showed inhibition on the viability and proliferation of lung carcinoma cells (A549) in time-dependent manners, but no cytotoxicity to human liver cell (HL-7702). Moreover, COS could significantly increase Bax expression of A549 cells while decreasing Bcl-2 expression. COS supplementation significantly inhibited the growth of Lewis tissues and promoted necrosis of tumor cells in vivo. After treatment with COS, significantly elevated concentrations of Bax and reduced expression of Bcl-2 in tumor tissues, as well as elevated levels of TNF-α, IL-2, Fas and Fas-L in mice serum were observed (p < 0.05). In conclusion, COS had certain anti-tumor effects and potential application as a synergic functional food ingredient to prevent cancer.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.