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Advanced Materials (Deerfield Beach,... Oct 2023The aberrant mechanical microenvironment in degenerated tissues induces misdirection of cell fate, making it challenging to achieve efficient endogenous regeneration....
The aberrant mechanical microenvironment in degenerated tissues induces misdirection of cell fate, making it challenging to achieve efficient endogenous regeneration. Herein, a hydrogel microsphere-based synthetic niche with integrated cell recruitment and targeted cell differentiation properties via mechanotransduction is constructed . Through the incorporation of microfluidics and photo-polymerization strategies, fibronectin (Fn) modified methacrylated gelatin (GelMA) microspheres are prepared with the independently tunable elastic modulus (1-10Kpa) and ligand density (2 and 10 µg mL ), allowing a wide range of cytoskeleton modulation to trigger the corresponding mechanobiological signaling. The combination of the soft matrix (2Kpa) and low ligand density (2 µg mL ) can support the nucleus pulposus (NP)-like differentiation of intervertebral disc (IVD) progenitor/stem cells by translocating Yes-associated protein (YAP), without the addition of inducible biochemical factors. Meanwhile, platelet-derived growth factor-BB (PDGF-BB) is loaded onto Fn-GelMA microspheres (PDGF@Fn-GelMA) via the heparin-binding domain of Fn to initiate endogenous cell recruitment. In in vivo experiments, hydrogel microsphere-niche maintained the IVD structure and stimulated matrix synthesis. Overall, this synthetic niche with cell recruiting and mechanical training capabilities offered a promising strategy for endogenous tissue regeneration.
Topics: Hydrogels; Microspheres; Ligands; Mechanotransduction, Cellular; Stem Cells; Cell Differentiation; Gelatin
PubMed: 37230467
DOI: 10.1002/adma.202300180 -
Biomaterials Aug 2023Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp...
Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp regeneration. In this study, we provided an atlas of the non-cultured and monolayer cultured dental pulp cells with single-cell RNA sequencing and analysis. Monolayer cultured dental pulp cells cluster more closely together than non-cultured dental pulp cells, suggesting a lower heterogeneous population with relatively consistent clusters and similar cellular composition. We successfully fabricated hDPSC-loaded microspheres by layer-by-layer photocuring with a digital light processing (DLP) printer. These hDPSC-loaded microspheres have improved stemness and higher multi-directional differentiation potential, including angiogenic, neurogenic, and odontogenic differentiation. The hDPSC-loaded microspheres could promote spinal cord regeneration in rat spinal cord injury models. Moreover, in heterotopic implantation tests on nude mice, CD31, MAP2, and DSPP immunofluorescence signals were observed, implying the formation of vascular, neural, and odontogenetic tissues. In situ experiments in minipigs demonstrated highly vascularized dental pulp and uniformly arranged odontoblast-like cells in root canals of incisors. In short, hDPSC-loaded microspheres can promote full-length dental pulp regeneration at the root canals' coronal, middle, and apical sections, particularly for blood vessels and nerve formation, which is a promising therapeutic strategy for necrotic pulp.
Topics: Mice; Rats; Swine; Animals; Dental Pulp; Swine, Miniature; Microspheres; Regeneration; Mice, Nude; Stem Cells; Cell Differentiation; Spinal Cord; Cells, Cultured
PubMed: 37172537
DOI: 10.1016/j.biomaterials.2023.122137 -
Advanced Materials (Deerfield Beach,... Feb 2024Inflammaging is deeply involved in aging-related diseases and can be destructive during aging. The maintenance of pH balance in the extracellular microenvironment can...
Inflammaging is deeply involved in aging-related diseases and can be destructive during aging. The maintenance of pH balance in the extracellular microenvironment can alleviate inflammaging and repair aging-related tissue damage. In this study, the hydrogen ion capturing hydrogel microsphere (GMNP) composed of mineralized transforming growth factor-β (TGF-β) and catalase (CAT) nanoparticles is developed via biomimetic mineralization and microfluidic technology for blocking the NLRP3 cascade axis in inflammaging. This GMNP can neutralize the acidic microenvironment by capturing excess hydrogen ions through the calcium carbonate mineralization layer. Then, the subsequent release of encapsulated TGF-β and CAT can eliminate both endogenous and exogenous stimulus of NLRP3, thus suppressing the excessive activation of inflammaging. In vitro, GMNP can suppress the excessive activation of the TXNIP/NLRP3/IL-1β cascade axis and enhance extracellular matrix (ECM) synthesis in nucleus pulposus cells. In vivo, GMNP becomes a sustainable and stable niche with microspheres as the core to inhibit inflammaging and promote the regeneration of degenerated intervertebral discs. Therefore, this hydrogen ion-capturing hydrogel microsphere effectively reverses inflammaging by interfering with the excessive activation of NLRP3 in the degenerated tissues.
Topics: Humans; NLR Family, Pyrin Domain-Containing 3 Protein; Intervertebral Disc Degeneration; Protons; Microspheres; Hydrogels; Transforming Growth Factor beta
PubMed: 37699155
DOI: 10.1002/adma.202306105 -
Journal of Drugs in Dermatology : JDD Sep 2023Regenerative aesthetics aims to restore the structure and function of aging skin. Two products, Radiesse (CaHA) and NCTF 135 HA (micronutrient mesotherapy) have been...
Regenerative aesthetics aims to restore the structure and function of aging skin. Two products, Radiesse (CaHA) and NCTF 135 HA (micronutrient mesotherapy) have been established as minimally invasive treatments that restore the structure and function of various skin components. It has been anecdotally observed by the authors, however, that some patients respond suboptimally to regenerative treatments without a clear indication as to why. It was hypothesized that micronutrient deficiencies in some patients may contribute to their lack of responsiveness and that a concurrent delivery of amino acids and co-enzymes may create a nutritional reservoir necessary for optimal protein synthesis. Noting that CaHA is known to drive the regeneration of extracellular matrix proteins, the aim of this case series was to investigate if “priming” the skin with NCTF 135 HA could lead to enhanced clinical effects of CaHA. The combination treatment resulted in improvements in panfacial aesthetics, skin laxity, wrinkle severity, skin luminosity, hyperpigmentation, and in skin and subcutis thicknesses in 100% of patients following a single treatment. This study is the first to introduce skin priming via diluting a regenerative biostimulator treatment with an amino acid-based diluent. Citation: Theodorakopoulou E, McCarthy A, Perico V, et al. Optimizing skin regenerative response to calcium hydroxylapatite microspheres via poly-micronutrient priming. J Drugs Dermatol. 2023;22(9):925-934. doi:10.36849/JDD.7405.
Topics: Humans; Micronutrients; Calcium; Durapatite; Microspheres; Skin
PubMed: 37683067
DOI: 10.36849/JDD.7405 -
Advanced Healthcare Materials Dec 2023Full-range therapeutic regimens for osteoarthritis (OA) should consider organs (joints)-tissues (cartilage)-cells (chondrocytes)-organelles cascade, of which the...
Full-range therapeutic regimens for osteoarthritis (OA) should consider organs (joints)-tissues (cartilage)-cells (chondrocytes)-organelles cascade, of which the subcellular mitochondria dominate eukaryotic cells' fate, and thus causally influence OA progression. However, the dynamic regulation of mitochondrial rise and demise in impaired chondrocytes and the exact role of mitochondrial metronome sirtuins 3 (SIRT3) is not clarified. Herein, chondrocytes are treated with SIRT3 natural agonist dihydromyricetin (DMY) or chemical antagonist 3-TYP, respectively, to demonstrate the positive action of SIRT3 on preserving cartilage extracellular matrix (ECM). Molecular mechanical investigations disclose that SIRT3-induced chondroprotection depended on the repression of mitochondrial apoptosis (mtApoptosis) and the activation of mitophagy. Inspired by the high-level matrix proteinases and reactive oxygen species (ROS) in the OA environment, by anchoring gelatin methacrylate (GelMA) and benzenediboronic acid (PBA) to hyaluronic acid methacrylate (HAMA) with microfluidic technology, a dual-responsive hydrogel microsphere laden with DMY is tactfully fabricated and named as DMY@HAMA-GelMA-PBA (DMY@HGP). In vivo injection of DMY@HGP ameliorated cartilage abrasion and subchondral bone sclerosis, as well as promoted motor function recovery in post-traumatic OA (PTOA) model via recouping endogenous mtApoptosis and mitophagy balance. Overall, this study unveils a novel mitochondrial dynamic-oriented strategy, holding great promise for the precision treatment of OA.
Topics: Humans; Mitophagy; Sirtuin 3; Hydrogels; Microspheres; Osteoarthritis; Chondrocytes; Mitochondria; Apoptosis; Hyaluronic Acid; Methacrylates
PubMed: 37696643
DOI: 10.1002/adhm.202302475 -
Nature Communications Jul 2023The response rate of pancreatic cancer to chemotherapy or immunotherapy pancreatic cancer is low. Although minimally invasive irreversible electroporation (IRE) ablation...
The response rate of pancreatic cancer to chemotherapy or immunotherapy pancreatic cancer is low. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for irresectable pancreatic cancers, the immunosuppressive tumour microenvironment that characterizes this tumour type enables tumour recurrence. Thus, strengthening endogenous adaptive antitumour immunity is critical for improving the outcome of ablation therapy and post-ablation immune therapy. Here we present a hydrogel microsphere vaccine that amplifies post-ablation anti-cancer immune response via releasing its cargo of FLT3L and CD40L at the relatively lower pH of the tumour bed. The vaccine facilitates migration of the tumour-resident type 1 conventional dendritic cells (cDC1) to the tumour-draining lymph nodes (TdLN), thus initiating the cDC1-mediated antigen cross-presentation cascade, resulting in enhanced endogenous CD8 T cell response. We show in an orthotopic pancreatic cancer model in male mice that the hydrogel microsphere vaccine transforms the immunologically cold tumour microenvironment into hot in a safe and efficient manner, thus significantly increasing survival and inhibiting the growth of distant metastases.
Topics: Hydrogels; Microspheres; Pancreatic Neoplasms; Male; Animals; Mice; Cell Line, Tumor; Mice, Inbred C57BL; Cancer Vaccines; Electroporation; CD8-Positive T-Lymphocytes
PubMed: 37433774
DOI: 10.1038/s41467-023-39759-w -
Biomedical Materials (Bristol, England) Oct 2023Bone/cartilage repair and regeneration have been popular and difficult issues in medical research. Tissue engineering is rapidly evolving to provide new solutions to... (Review)
Review
Bone/cartilage repair and regeneration have been popular and difficult issues in medical research. Tissue engineering is rapidly evolving to provide new solutions to this problem, and the key point is to design the appropriate scaffold biomaterial. In recent years, microsphere-based scaffolds have been considered suitable scaffold materials for bone/cartilage injury repair because microporous structures can form more internal space for better cell proliferation and other cellular activities, and these composite scaffolds can provide physical/chemical signals for neotissue formation with higher efficiency. This paper reviews the research progress of microsphere-based scaffolds in bone/chondral tissue engineering, briefly introduces types of microspheres made from polymer, inorganic and composite materials, discusses the preparation methods of microspheres and the exploration of suitable microsphere pore size in bone and cartilage tissue engineering, and finally details the application of microsphere-based scaffolds in biomimetic scaffolds, cell proliferation and drug delivery systems.
Topics: Tissue Engineering; Microspheres; Biocompatible Materials; Tissue Scaffolds; Cartilage
PubMed: 37751762
DOI: 10.1088/1748-605X/acfd78 -
Carbohydrate Polymers Apr 2024Chitin microspheres (CMs) have attracted increasing attention due to their biocompatibility, uniform size and shape, large surface area, and porous structure.... (Review)
Review
Chitin microspheres (CMs) have attracted increasing attention due to their biocompatibility, uniform size and shape, large surface area, and porous structure. Considerable research efforts have been focused on developing CMs and promoting their applications in various areas. In this context, this review aims to describe the most recent progress in the fabrication and application of CMs. Different routes that can be used to prepare CMs, such as the drip method and the emulsion method, are emphatically introduced. Moreover, the applications of CMs as drug delivery systems, wound dressings, three-dimensional (3D) scaffolds, water purification, and functional supporting materials in the fields of biomedicine, tissue engineering, environmental protection, and energy storage are also highlighted. We hope this review can provide a comprehensive and useful database for further innovation of CMs.
Topics: Tissue Scaffolds; Chitin; Microspheres; Tissue Engineering; Drug Delivery Systems
PubMed: 38286547
DOI: 10.1016/j.carbpol.2023.121773 -
Drug Discoveries & Therapeutics Jul 2023The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations.... (Review)
Review
The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations. However, harmful solvents must be used to produce certain formulations. For instance, methylene chloride has been used in the fabrication of polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) microspheres. This review highlights the latest advances in the strategy of PLA or PLGA microsphere production from non-halogenated solvents and describes advantages and limitations of these methods. The study also discusses the development of dry fabrication techniques for microsphere fabrication and the positioning of conventional and dry fabrication in the containment concept for workers' safety.
Topics: Humans; Polylactic Acid-Polyglycolic Acid Copolymer; Polyglycolic Acid; Lactic Acid; Microspheres; Polyesters; Solvents; Particle Size
PubMed: 37245983
DOI: 10.5582/ddt.2023.01008 -
Advanced Healthcare Materials Nov 2023Periodontitis is a prevalent dental disease marked by progressive destruction of tooth-supporting tissues, and the recovery of bone defects after periodontitis remains...
Periodontitis is a prevalent dental disease marked by progressive destruction of tooth-supporting tissues, and the recovery of bone defects after periodontitis remains challenging. Although stem cell-based therapy is a promising treatment for periodontal tissue regeneration, the function of mesenchymal stem cells is constantly impaired by the inflammatory microenvironment, leading to compromised treatment outcomes. Herein, calcitonin gene-related peptide (CGRP)-loaded porous microspheres (PMs) are prepared to protect bone marrow mesenchymal stem cells (BMSCs) against inflammatory mediators in periodontitis. The released CGRP can effectively ameliorate the inflammation-induced dysfunction of BMSCs, which may involve suppressing the ROS (reactive oxygen species)/NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3)/Caspase-1 (CASP1) pathway. Moreover, the porous architecture of PMs provides effective cell-carrying capacity and physical protection for BMSCs during transplantation. In vivo experiments demonstrate that CGRP/BMSC-loaded PMs can effectively inhibit inflammation and improve osteogenic activity, resulting in better periodontal bone regeneration. This study focuses on the protection of stem cell function in the inflammatory microenvironment, which is important for stem cell-mediated tissue regeneration and repair under inflammatory conditions.
Topics: Humans; Calcitonin Gene-Related Peptide; Microspheres; Porosity; Bone Regeneration; Periodontitis; Osteogenesis; Mesenchymal Stem Cells; Inflammation; Cell Differentiation
PubMed: 37515813
DOI: 10.1002/adhm.202301366