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Small (Weinheim An Der Bergstrasse,... Apr 2023Paracrine is an important mechanism in mesenchymal stem cells (MSCs) that promotes tissue regeneration. However, anoikis is attributed to unsuitable adhesion...
Paracrine is an important mechanism in mesenchymal stem cells (MSCs) that promotes tissue regeneration. However, anoikis is attributed to unsuitable adhesion microenvironment hindered this paracrine effect. In this study, a living and injectable porous hydrogel microsphere with long-term paracrine activity is constructed via the freeze-drying microfluidic technology and the incorporation of platelet-derived growth factor-BB (PDGF-BB) and exogenous MSCs. Benefiting from the porous structure and superior mechanical property of methacrylate gelatin (GelMA) hydrogel microspheres (GMs), exogenous stem cells are able to adhere and proliferate on GMs, thereby facilitating cell-to-extracellular matrix (ECM) and cell-to-cell interactions and enhancing paracrine effect. Furthermore, the sustained release of PDGF-BB can recruit endogenous MSCs to prolong the paracrine activity of the living GMs. In vitro and in vivo experiments validated that the living GMs exhibit superior secretion properties and anti-inflammatory efficacy and can attenuate osteoarthritis (OA) progression by favoring the adherent microenvironment and utilizing the synergistic effect of exogenous and endogenous MSCs. Overall, a living injectable porous hydrogel microsphere that can enhance the paracrine activity of stem cells is fabricated and anticipated to hold the potential of future clinical translation in OA and other diseases.
Topics: Microspheres; Becaplermin; Porosity; Biocompatible Materials; Cartilage; Hydrogels
PubMed: 36651038
DOI: 10.1002/smll.202207211 -
Nano Letters Mar 2021Although injectable hydrogel microsphere has demonstrated tremendous promise in clinical applications, local overactive inflammation in degenerative diseases could...
Although injectable hydrogel microsphere has demonstrated tremendous promise in clinical applications, local overactive inflammation in degenerative diseases could jeopardize biomaterial implantation's therapeutic efficacy. Herein, an injectable "peptide-cell-hydrogel" microsphere was constructed by covalently coupling of APETx2 and further loading of nucleus pulposus cells, which could inhibit local inflammatory cytokine storms to regulate the metabolic balance of ECM . The covalent coupling of APETx2 preserved the biocompatibility of the microspheres and achieved a controlled release of APETx2 for more than 28 days in an acidic environment. By delivering "peptide-cell-hydrogel" microspheres to a rat degenerative intervertebral disc at 4 weeks, the expression of ASIC-3 and IL-1β was significantly decreased for 3.53-fold and 7.29-fold, respectively. Also, the content of ECM was significantly recovered at 8 weeks. In summary, the proposed strategy provides an effective approach for tissue regeneration under overactive inflammatory responses.
Topics: Animals; Biocompatible Materials; Hydrogels; Inflammation; Microspheres; Nucleus Pulposus; Rats
PubMed: 33543616
DOI: 10.1021/acs.nanolett.0c04713 -
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 -
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 -
Advanced Science (Weinheim,... May 2023Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and is featured by the imbalance between intraosseous vascularization and bone...
Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and is featured by the imbalance between intraosseous vascularization and bone metabolism. In this study, a pH-responsive shell-core structured micro/nano-hydrogel microspheres loaded with polyhedral oligomeric silsesquioxane (POSS) using gas microfluidics and ionic cross-linking technology are developed. This micro/nano-hydrogel microsphere system (PDAP@Alg/Cs) can achieve oral delivery, intragastric protection, intestinal slow/controlled release, active targeting to bone tissue, and thus negatively affecting intraosseous angiogenesis and osteoclastogenesis. According to biodistribution data, PDAP@Alg/Cs can successfully enhance drug intestinal absorption and bioavailability through intestine adhesion and bone targeting after oral administration. In vitro and in vivo experiments reveal that PDAP@Alg/Cs promoted type H vessel formation and inhibited bone resorption, effectively mitigating bone loss by activating HIF-1α/VEGF signaling pathway and promoting heme oxygenase-1 (HO-1) expression. In conclusion, this novel oral micro/nano-hydrogel microsphere system can simultaneously accelerate intraosseous vascularization and decrease bone resorption, offering a brand-new approach to prevent postmenopausal osteoporosis.
Topics: Female; Humans; Hydrogels; Microspheres; Osteoporosis, Postmenopausal; Tissue Distribution; Bone and Bones; Bone Resorption
PubMed: 36967561
DOI: 10.1002/advs.202207381 -
Annual Review of Biomedical Engineering Jun 2017Microspheres have long been used in drug delivery applications because of their controlled release capabilities. They have increasingly served as the fundamental... (Review)
Review
Microspheres have long been used in drug delivery applications because of their controlled release capabilities. They have increasingly served as the fundamental building block for fabricating scaffolds for regenerative engineering because of their ability to provide a porous network, offer high-resolution control over spatial organization, and deliver growth factors/drugs and/or nanophase materials. Because they provide physicochemical gradients via spatiotemporal release of bioactive factors and nanophase ceramics, microspheres are a desirable tool for engineering complex tissues and biological interfaces. In this review we describe various methods for microsphere fabrication and sintering, and elucidate how these methods influence both micro- and macroscopic scaffold properties, with a special focus on the nature of sintering. Furthermore, we review key applications of microsphere-based scaffolds in regenerating various tissues. We hope to inspire researchers to join a growing community of investigators using microspheres as tissue engineering scaffolds so that their full potential in regenerative engineering may be realized.
Topics: Animals; Biocompatible Materials; Cell Transplantation; Equipment Design; Guided Tissue Regeneration; Humans; Microspheres; Tissue Engineering; Tissue Scaffolds
PubMed: 28633566
DOI: 10.1146/annurev-bioeng-071516-044712 -
Chemistry, An Asian Journal Oct 2022Key Laboratory for Ultrafine Materials of Ministry of Education Centre for Biomedical Technologies Current tissue engineering technology aims to achieve the regeneration... (Review)
Review
Key Laboratory for Ultrafine Materials of Ministry of Education Centre for Biomedical Technologies Current tissue engineering technology aims to achieve the regeneration of human tissues, which integrates the key factors such as scaffolds, cells and biomolecules. Among these key factors, the development of high-performance scaffolds is the basis for the success of tissue engineering strategies. In the past decades, hydrogel scaffolds have been developed rapidly and widely used in biomedical field, however, their drawbacks have also been revealed, which shows that a single hydrogel scaffold cannot meet the excellent performance required in the field of tissue engineering. Recently, microspheres have been further engineered to fabricate structurally and functionally reliable artificial three-dimensional scaffolds of desired shape with enhanced specific biological functions. Therefore, the effective combination of hydrogel and microspheres can facilitate the development of high-performance scaffolds for tissue engineering and further fine-tuning the composite structure, which is expected to solve the dilemma faced by a single scaffold. In this review paper, we systematically summurized the type and preparation method for synthesis of hydrogel and microsphere materials commonly used in developing microsphere-containing hydrogel scaffolds. We then reviewed the broad application of these hybrid scaffolds in various fields of tissue engineering, followed by a summary and perspective on future directions.
Topics: Humans; Tissue Engineering; Hydrogels; Microspheres
PubMed: 35909078
DOI: 10.1002/asia.202200630 -
International Journal of Molecular... Apr 2023Tissue injury, one of the most common traumatic injuries in daily life, easily leads to secondary wound infections. To promote wound healing and reduce scarring, various... (Review)
Review
Tissue injury, one of the most common traumatic injuries in daily life, easily leads to secondary wound infections. To promote wound healing and reduce scarring, various kinds of wound dressings, such as gauze, bandages, sponges, patches, and microspheres, have been developed for wound healing. Among them, microsphere-based tissue dressings have attracted increasing attention due to the advantage of easy to fabricate, excellent physicochemical performance and superior drug release ability. In this review, we first introduced the common methods for microspheres preparation, such as emulsification-solvent method, electrospray method, microfluidic technology as well as phase separation methods. Next, we summarized the common biomaterials for the fabrication of the microspheres including natural polymers and synthetic polymers. Then, we presented the application of the various microspheres from different processing methods in wound healing and other applications. Finally, we analyzed the limitations and discussed the future development direction of microspheres in the future.
Topics: Humans; Microspheres; Wound Healing; Cicatrix; Polymers; Biocompatible Materials
PubMed: 37108482
DOI: 10.3390/ijms24087319 -
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 -
Seminars in Nuclear Medicine Mar 2022Radiomicrosphere Therapy (RMT) refers to a liver-directed therapeutic modality based on the intrahepatic arterial administration of radiolabeled microspheres. There is a... (Review)
Review
Radiomicrosphere Therapy (RMT) refers to a liver-directed therapeutic modality based on the intrahepatic arterial administration of radiolabeled microspheres. There is a need for standardization of the terminology of RMT. A descriptive identifier should first name the radioisotope, then the chemical formulation of the microsphere, and lastly add the term RMT that indicates the therapeutic modality. At present, clinically available options include |Y-90| |Resin| |RMT|, |Y-90| |Glass| |RMT| and |Ho-166| |PLLA| |RMT|. The latter is available in Europe and is being considered for clearance by the FDA in the United States. Preclinical studies with |Re-188| |PLLA| |RMT| are underway. Dosimetric considerations are strongly tied to both the type of the radioisotope and the chemical composition of the microsphere type. This review will focus on Y-90 resin and glass RMT, the history, dosimetry, clinical use, and controversies.
Topics: Embolization, Therapeutic; Humans; Liver Neoplasms; Microspheres; Radioisotopes; Radiometry; Rhenium; Yttrium Radioisotopes
PubMed: 35148897
DOI: 10.1053/j.semnuclmed.2021.12.009