Biomaterials research最新文献

Background: Drug nanocarriers can markedly reduce the toxicities and side effects of encapsulated chemotherapeutic drugs in the clinic. However, these drug nanocarriers have little effect on eradicating breast cancer stem cells (BCSCs). Although compounds that can inhibit BCSCs have been reported, these compounds are difficult to use as carriers for the widespread delivery of conventional chemotherapeutic drugs.

Methods: Herein, we synthesize a polymeric nanocarrier, hyaluronic acid-block-poly (curcumin-dithiodipropionic acid) (HA-b-PCDA), and explore the use of HA-b-PCDA to simultaneously deliver chemotherapeutic drugs and eradicate BCSCs.

Results: Based on molecular docking and molecular dynamics studies, HA-b-PCDA delivers 35 clinical chemotherapeutic drugs. To further verify the drug deliver ability of HA-b-PCDA, doxorubicin, paclitaxel, docetaxel, gemcitabine and camptothecin are employed as model drugs to prepare nanoparticles. These drug-loaded HA-b-PCDA nanoparticles significantly inhibit the proliferation and stemness of BCSC-enriched 4T1 mammospheres. Moreover, doxorubicin-loaded HA-b-PCDA nanoparticles efficiently inhibit tumor growth and eradicate approximately 95% of BCSCs fraction in vivo. Finally, HA-b-PCDA eradicates BCSCs by activating Hippo and inhibiting the JAK2/STAT3 pathway.

Conclusion: HA-b-PCDA is a polymeric nanocarrier that eradicates BCSCs and potentially delivers numerous clinical chemotherapeutic drugs.

Background: Bone tissue regeneration is regulated by complex events, including inflammation, osteoinduction, and remodeling. Therefore, to induce the complete restoration of defective bone tissue, biomaterials with the ability to regulate the collective bone regenerative system are beneficial. Although some studies conclude that reducing reactive oxygen species created a favorable environment for bone regeneration by controlling inflammation, biomaterials that can simultaneously promote osteogenesis and regulate inflammation have not been developed. Herein, we describe the development of a multi-functional nanoparticle and its hydrogel composite with osteoinductive, anti-inflammatory, and osteoclast-maturation regulatory functions for enhanced bone regeneration.

Methods: Tannic acid-mineral nanoparticles (TMP) were prepared by self-assembly of tannic acid in an ion-rich simulated body fluid containing Ca²⁺ and PO₄^3-. Particles with a diameter of 443 ± 91 nm were selected for their stable spherical morphology and minimal tendency to aggregate. The particles were homogeneously embedded within a gelatin-based cryogel (TMP/Gel) to be used in further experiments. The osteoinductive properties, anti-inflammatory and osteoclast-maturation regulatory functions in vitro were tested by culturing corresponding cells on either TMP/Gel or a gelatin-based cryogel without the particles (Gel). For in vivo analyses, a murine calvarial defect model was used. Statistical analyses were carried out using a Graphpad Prism 7 software (San Diego, CA, USA) to perform one-way analysis of variance ANOVA with Tukey's honest significant difference test and a Student's t-test (for two variables) (P < 0.05).

Results: Excellent biocompatibility and radical scavenging abilities were exhibited by the TMP/Gel. The expression of osteogenic mRNA is significantly increased in human adipose-derived stem cells seeded on the TMP/Gel compared to those without the particles. Furthermore, RAW264.7 cells seeded on the TMP/Gel displayed significantly lower-than-normal levels of pro-inflammatory and osteoclastogenic genes. Finally, the in vivo results indicated that, compared with the cryogel with no anti-inflammatory effect, the TMP/Gel significantly enhanced both the quality and quantity of newly formed bone, demonstrating the importance of combining anti-inflammation with osteoinduction.

Conclusion: Collectively, these findings suggest our nanoparticle-hydrogel composite could be an effective tool to regulate complex events within the bone healing process.

Molecular self-assembly has received considerable attention in biomedical fields as a simple and effective method for developing biomolecular nanostructures. Self-assembled nanostructures can exhibit high binding affinity and selectivity by displaying multiple ligands/receptors on their surface. In addition, the use of supramolecular structure change upon binding is an intriguing approach to generate binding signal. Therefore, many self-assembled nanostructure-based biosensors have been developed over the past decades, using various biomolecules (e.g., peptides, DNA, RNA, lipids) and their combinations with non-biological substances. In this review, we provide an overview of recent developments in the design and fabrication of self-assembling biomolecules for biosensing. Furthermore, we discuss representative electrochemical biosensing platforms which convert the biochemical reactions of those biomolecules into electrical signals (e.g., voltage, ampere, potential difference, impedance) to contribute to detect targets. This paper also highlights the successful outcomes of self-assembling biomolecules in biosensor applications and discusses the challenges that this promising technology needs to overcome for more widespread use.

Background: To overcome the limitations of current alternative therapies for chronic kidney disease (CKD), tissue engineering-mediated regeneration strategies have demonstrated the possibilities for complete kidney tissue regeneration. Given the challenges associated with the reproducibility of renal basal cells, the incorporation of intermediate mesoderm (IM) cells and bioactive materials to control bioactivities of cells with supported scaffolds should be considered as a viable approach to enable the regeneration of the complex kidney structure via renal differentiation.

Methods: We developed PMEZ scaffolds by combining crucial bioactive components, such as ricinoleic acid-grafted Mg(OH)₂ (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) integrated into biodegradable porous PLGA (P) platform. Additionally, we utilized differentiating extracellular vesicles (dEV) isolated during intermediate mesoderm differentiation into kidney progenitor cells, and IM cells were serially incorporated to facilitate kidney tissue regeneration through their differentiation into kidney progenitor cells in the 3/4 nephrectomy mouse model.

Results: The use of differentiating extracellular vesicles facilitated IM differentiation into kidney progenitor cells without additional differentiation factors. This led to improvements in various regeneration-related bioactivities including tubule and podocyte regeneration, anti-fibrosis, angiogenesis, and anti-inflammation. Finally, implanting PMEZ/dEV/IM scaffolds in mouse injury model resulted in the restoration of kidney function.

Conclusions: Our study has demonstrated that utilizing biodegradable PLGA-based scaffolds, which include multipotent cells capable of differentiating into various kidney progenitor cells along with supporting components, can facilitate kidney tissue regeneration in the mouse model that simulates CKD through 3/4 nephrectomy.

Rationale: To realize imaging-guided multi-modality cancer therapy with minimal side effects remains highly challenging.

Methods: We devised a bioinspired hollow nitrogen-doped carbon sphere anchored with individually dispersed Mn atoms (Mn/N-HCN) via oxidation polymerization with triton micelle as a soft template, followed by carbonization and annealing. Enzyme kinetic analysis and optical properties were performed to evaluate the imaging-guided photothermally synergized nanocatalytic therapy.

Results: Simultaneously mimicking several natural enzymes, namely peroxidase (POD), catalase (CAT), oxidase (OXD), and glutathione peroxidase (GPx), this nano-multizyme is able to produce highly cytotoxic hydroxyl radical (•OH) and singlet oxygen (¹O₂) without external energy input through parallel and series catalytic reactions and suppress the upregulated antioxidant (glutathione) in tumor. Furthermore, NIR-II absorbing Mn/N-HCN permits photothermal therapy (PTT), enhancement of CAT activity, and photoacoustic (PA) imaging to monitor the accumulation kinetics of the nanozyme and catalytic process in situ. Both in vitro and in vivo experiments demonstrate that near-infrared-II (NIR-II) PA-imaging guided, photothermally enhanced and synergized nanocatalytic therapy is efficient to induce apoptosis of cancerous cells and eradicate tumor tissue.

Conclusions: This study not only demonstrates a new method for effective cancer diagnosis and therapy but also provides new insights into designing multi-functional nanozymes.

Background: Recently, increased attention has been given on exosomes as ideal nanocarriers of drugs owing to their intrinsic properties that facilitate the transport of biomolecular cargos. However, large-scale exosome production remains a major challenge in the clinical application of exosome-based drug delivery systems. Considering its biocompatibility and stability, bovine milk is a suitable natural source for large-scale and stable exosome production. Because the active-targeting ability of drug carriers is essential to maximize therapeutic efficacy and minimize side effects, precise membrane functionalization strategies are required to enable tissue-specific delivery of milk exosomes with difficulty in post-isolation modification.

Methods: In this study, the membrane functionalization of a milk exosome platform modified using a simple post-insertion method was examined comprehensively. Exosomes were engineered from bovine milk (mExo) with surface-tunable modifications for the delivery of tumor-targeting doxorubicin (Dox). The surface modification of mExo was achieved through the hydrophobic insertion of folate (FA)-conjugated lipids.

Results: We have confirmed the stable integration of functionalized PE-lipid chains into the mExo membrane through an optimized post-insertion technique, thereby effectively enhancing the surface functionality of mExo. Indeed, the results revealed that FA-modified mExo (mExo-FA) improved cellular uptake in cancer cells via FA receptor (FR)-mediated endocytosis. The designed mExo-FA selectively delivered Dox to FR-positive tumor cells and triggered notable tumor cell death, as confirmed by in vitro and in vivo analyses.

Conclusions: This simple and easy method for post-isolation modification of the exosomal surface may be used to develop milk-exosome-based drug delivery systems.

Musculoskeletal disorders (MSDs), which include a range of pathologies affecting bones, cartilage, muscles, tendons, and ligaments, account for a significant portion of the global burden of disease. While pharmaceutical and surgical interventions represent conventional approaches for treating MSDs, their efficacy is constrained and frequently accompanied by adverse reactions. Considering the rising incidence of MSDs, there is an urgent demand for effective treatment modalities to alter the current landscape. Phototherapy, as a controllable and non-invasive technique, has been shown to directly regulate bone, cartilage, and muscle regeneration by modulating cellular behavior. Moreover, phototherapy presents controlled ablation of tumor cells, bacteria, and aberrantly activated inflammatory cells, demonstrating therapeutic potential in conditions such as bone tumors, bone infection, and arthritis. By constructing light-responsive nanosystems, controlled drug delivery can be achieved to enable precise treatment of MSDs. Notably, various phototherapy nanoplatforms with integrated imaging capabilities have been utilized for early diagnosis, guided therapy, and prognostic assessment of MSDs, further improving the management of these disorders. This review provides a comprehensive overview of the strategies and recent advances in the application of phototherapy for the treatment of MSDs, discusses the challenges and prospects of phototherapy, and aims to promote further research and application of phototherapy techniques.

Background: Mesenchymal stem cells (MSCs) have gained significant attention for diverse biomedical applications, including cell-based therapy. Hence, in vitro expansion of MSCs is critical; however, in vitro MSC culture, especially long-term culture, inevitably leads to significant loss of stemness, growth, and differentiation potential.

Method: Effects of mild heat treatment (HT) conditions (temperature, duration, and repetition) on the characteristics of adipose tissue-derived MSCs in vitro were systematically investigated. Characteristics of the MSCs subjected to the predetermined HT conditions (41 or 44ºC, 1 h, and 2X HT) were first analyzed in a single passage using various assays. In addition, the feasibility of HT for long-term MSC culture was studied. The RNA sequencing analyses were performed to elucidate the mechanism of HT effects on MSCs.

Results: A comprehensive exploration of various HT conditions revealed that specific mild HT at 41ºC or 44ºC for 1 h upregulated the expression of heat shock proteins and stemness markers and enhanced differentiation potentials. Furthermore, periodic mild HT extended the maintenance of growth rate and stemness of MSCs up to an additional 10 passages, which substantially retarded their spontaneous aging during subsequent in vitro culture. RNA sequencing analyses unveiled that HT downregulated genes associated with aging and apoptosis.

Conclusion: Our study successfully demonstrated that mild HT of MSCs has positive effects on their application in various biomedical fields, enhancing their capabilities and slowing down the aging process.

Studies have reported on the significance of copper incorporated nanomaterials (CINMs) in cancer theranostics and tissue regeneration. Given their unique physicochemical properties and tunable nanostructures, CINMs are used in photothermal therapy (PTT) and photothermal-derived combination therapies. They have the potential to overcome the challenges of unsatisfactory efficacy of conventional therapies in an efficient and non-invasive manner. This review summarizes the recent advances in CINMs-based PTT in biomedicine. First, the classification and structure of CINMs are introduced. CINMs-based PTT combination therapy in tumors and PTT guided by multiple imaging modalities are then reviewed. Various representative designs of CINMs-based PTT in bone, skin and other organs are presented. Furthermore, the biosafety of CINMs is discussed. Finally, this analysis delves into the current challenges that researchers face and offers an optimistic outlook on the prospects of clinical translational research in this field. This review aims at elucidating on the applications of CINMs-based PTT and derived combination therapies in biomedicine to encourage future design and clinical translation.

Background: Triple-negative breast cancer (TNBC) is an aggressive, metastatic and apparently drug-resistant subtype of breast cancer with a higher immune response compared to other types of breast cancer. Photodynamic therapy (PDT) has been gaining popularity for its non-invasive nature, minimal side effects, and spatiotemporally controlled benifits. The use of metal-organic frameworks (MOFs) loaded with programmed death-ligand 1 inhibitors (iPD-L1) offers the possibility of combining PDT with immunotherapy.

Method: Here, we construct PCN-224, a MOFs with good biocompatibility and biodegradability for the delivery of the PD-L1 small molecule inhibitor BMS-202 to achieve a synergistic anti-tumor strategy of PDT and immunotherapy. Hyaluronic acid (HA) modified PEG (HA-PEG) was synthesized for the outer layer modification of the nanocomplex, which prolongs its systemic circulation time.

Results: In vitro cellular experiments show that the nanocomplexes irradiated by 660 nm laser has a strong ability to produce singlet oxygen, which effectively induce PDT. PDT with strong immunogenicity leads to tumor necrosis and apoptosis, and induces immunogenic cell death, which causes tumor cells to release danger associated molecular patterns. In combination with iPD-L1, the combination therapy stimulates dendritic cell maturation, promotes T-cell activation and intratumoral infiltration, and reshapes the tumor immune microenvironment to achieve tumor growth inhibition and anti-distant tumor progression.

Conclusions: MOFs-based nano-systems as a platform for combination therapy offer a potentially effective strategy for the treatment of TNBC with high metastatic rates.