Nanoclay-Composite Hydrogels for Bone Tissue Engineering.

Nanoclay-composite hydrogels represent a promising avenue for advancing bone tissue engineering. Traditional hydrogels face challenges in providing mechanical strength, biocompatibility, and bioactivity necessary for successful bone regeneration. The incorporation of nanoclay into hydrogel matrices offers a potential unique solution to these challenges.

Black Phosphorus-Based Dynamic Self-Healing Hydrogel to Integrate Demineralized Bone Matrix and Noggin-Targeting siRNA for Synergistic Osteogenesis.

Although a demineralized bone matrix (DBM) is often used as an alternative to an autologous bone graft, its clinical application is still hampered by easy dispersion of DBM particles and insufficient osteoinductivity in the defect site. Herein, we designed a self-healing hydrogel for DBM that can rapidly restore its structural integrity after damage based on amino-rich black phosphorus (BP) nanosheets and aldehyde-functionalized hyaluronic acid (AHA). Given the increased expression of bone morphogenetic protein (BMP) antagonists by DBM stimulation, the osteogenic potency of DBM in the hydrogel carrier was further enhanced by abrogating the BMP antagonism.

Self-Assembled Nanocomposite Hydrogels as Carriers for Demineralized Bone Matrix Particles and Enhanced Bone Repair.

Demineralized bone matrix (DBM) has been widely used as an allogeneic alternative to autologous bone graft for bone repair. However, more extensive use of DBM is limited due to its particulate nature after demineralization and rapid particle dispersion following irrigation, resulting in unpredictable osteoinductivity. Here, a new design of injectable hydrogel carriers for DBM that combine self-healing ability and osteogenic properties based on the self-assembly of guanidinylated hyaluronic acid and silica-rich nanoclays is reported.

Starch-Based Hydrogels as a Drug Delivery System in Biomedical Applications.

Starch-based hydrogels have gained significant attention in biomedical applications as a type of drug delivery system due to their biocompatibility, biodegradability, and ability to absorb and release drugs. Starch-based hydrogels can serve as effective carriers for pharmaceutical compounds such as drugs and proteins to develop drug-loaded hydrogel systems, providing controlled release over an extended period. The porous structure of a hydrogel allows for the diffusion of drugs, ensuring sustained and localized delivery to the target site.

Stem Cell-Derived Extracellular Vesicles for Cancer Therapy and Tissue Engineering Applications.

Recently, stem cells and their secretomes have attracted great attention in biomedical applications, particularly extracellular vesicles (EVs). EVs are secretomes of cells for cell-to-cell communication. They play a role as intercellular messengers as they carry proteins, nucleic acids, lipids, and therapeutic agents.

Complementary modulation of BMP signaling improves bone healing efficiency.

The bone morphogenetic protein (BMP) signaling pathway plays a crucial role in bone development and regeneration. While BMP-2 is widely used as an alternative to autograft, its clinical application has raised concerns about adverse side effects and deteriorated bone quality. Therefore, there is a need to develop more sophisticated approaches to regulate BMP signaling and promote bone regeneration.

Recent Progress in Hyaluronic-Acid-Based Hydrogels for Bone Tissue Engineering.

Hydrogel-based bone tissue engineering is a potential strategy for treating bone abnormalities and fractures. Hyaluronic acid (HA) is a natural polymer that is widely distributed in the human body and plays a significant role in numerous physiological processes such as cell migration, tissue hydration, and wound healing. Hydrogels based on HA and its derivatives have gained popularity as potential treatments for bone-related diseases.

Silver-Composited Polydopamine Nanoparticles: Antibacterial and Antioxidant Potential in Nanocomposite Hydrogels.

(1) Background: Infections of pathogenic microorganisms can be life-threatening due to delayed healing or even worsening conditions in tissue engineering and regenerative medicine. The excessive presence of reactive oxygen species in damaged and infected tissues causes a negative inflammatory response, resulting in failed healing. Thus, the development of hydrogels with antibacterial and antioxidant abilities for the treatment of infectious tissues is in high demand.

Bone-Targeting Exosome Mimetics Engineered by Bioorthogonal Surface Functionalization for Bone Tissue Engineering.

Extracellular vesicles have received a great interest as safe biocarriers in biomedical engineering. There is a need to develop more efficient delivery strategies to improve localized therapeutic efficacy and minimize off-target adverse effects. Here, exosome mimetics (EMs) are reported for bone targeting involving the introduction of hydroxyapatite-binding moieties through bioorthogonal functionalization.

Solubilized chlorin e6-layered double hydroxide complex for anticancer photodynamic therapy.

Background: Layered double hydroxides (LDHs) are one type of 2-dimensional material with unique structure and strongly positive surface charge. Particularly, LDHs can be exfoliated by mono-layered double hydroxides (MLHs) as a single layer, showing an increased surface area. Therefore, there is a large focus on LDHs for drug delivery applications.

Hemagglutinin Nanoparticulate Vaccine with Controlled Photochemical Immunomodulation for Pathogenic Influenza-Specific Immunity.

Recently, viral infectious diseases, including COVID-19 and Influenza, are the subjects of major concerns worldwide. One strategy for addressing these concerns focuses on nasal vaccines, which have great potential for achieving successful immunization via safe, easy, and affordable approaches. However, conventional nasal vaccines have major limitations resulting from fast removal when pass through nasal mucosa and mucociliary clearance hindering their effectiveness.

Bioactive Scaffolds Integrated with Liposomal or Extracellular Vesicles for Bone Regeneration.

With population aging and increased life expectancy, an increasing number of people are facing musculoskeletal health problems that necessitate therapeutic intervention at defect sites. Bone tissue engineering (BTE) has become a promising approach for bone graft substitutes as traditional treatments using autografts or allografts involve clinical complications. Significant advancements have been made in developing ideal BTE scaffolds that can integrate bioactive molecules promoting robust bone repair.

Sulfonate Hydrogel-siRNA Conjugate Facilitates Osteogenic Differentiation of Mesenchymal Stem Cells by Controlled Gene Silencing and Activation of BMP Signaling.

Hydrogels have been widely used in bone tissue engineering due to their tunable characteristics that allow facile modifications with various biochemical properties to support cell growth and guide proper cell functions. Herein, we report a design of hydrogel-siRNA conjugate that facilitates osteogenesis via gene silencing and activation of bone morphogenetic protein (BMP) signaling. A sulfonate hydrogel is prepared by modifying chitosan with sulfoacetic acid to mimic a natural sulfated polysaccharide and to provide a hydrogel surface that enables BMP binding.

Development of a Biomaterial Scaffold Integrated with Osteoinductive Oxysterol Liposomes to Enhance Hedgehog Signaling and Bone Repair.

Bone repair requires the tightly regulated control of multiple intrinsic and extrinsic cell types and signaling pathways. One of the positive regulatory signaling pathways in membranous and endochondral bone healing is the Hedgehog (Hh) signaling family. Here, a novel therapeutic liposomal delivery vector was developed by self-assembly of an Hh-activating cholesterol analog with an emulsifier, along with the addition of Smoothened agonist (SAG) as a drug cargo, for the enhancement of Hh signaling in bone regeneration.

Enhanced Osteoinductivity of Demineralized Bone Matrix with Noggin Suppression in Polymer Matrix.

Demineralized bone matrix (DBM), a potential alternative to autologous bone-graft, has been increasingly used for clinical bone repair; however, its application in larger defects isn't successful partly due to the rapid dispersion of DBM particles and relatively lower osteoinductivity. Here, a novel strategy is created to complement the osteoinductivity of DBM by incorporating DBM in biopolymer hydrogel combined with the abrogation of BMP antagonism. Combined treatment of DBM + noggin-suppression displays increased osteogenic potency of human bone marrow mesenchymal stem cells (hBMSCs) .

Inspired by nature: facile design of nanoclay-organic hydrogel bone sealant with multifunctional properties for robust bone regeneration.

Bone repair is a complex process involving the sophisticated interplay of osteogenic stem cells, extracellular matrix, and osteoinductive factors, and it is affected by bacterial toxins and oxidative stress. Inspired by the nature of plant-derived phytochemicals and inorganic-organic analogues of the bone extracellular matrix, we report herein the facile design of a nanoclay-organic hydrogel bone sealant (NoBS) that integrates multiple physico-chemical cues for bone regeneration into a single system. Assembly of phytochemical-modified organic chitosan and silica-rich inorganic nanoclay serves as highly biocompatible and osteoconductive extracellular matrix mimics.

Trb3 controls mesenchymal stem cell lineage fate and enhances bone regeneration by scaffold-mediated local gene delivery.

Aberrant lineage commitment of mesenchymal stem cells (MSCs) in marrow contributes to abnormal bone formation due to reduced osteogenic and increased adipogenic potency. While several major transcriptional factors associated with lineage differentiation have been found during the last few decades, the molecular switch for MSC fate determination and its role in skeletal regeneration remains largely unknown, limiting creation of effective therapeutic approaches. Tribbles homolog 3 (Trb3), a member of tribbles family pseudokinases, is known to exert diverse roles in cellular differentiation.

Dual Functional Lysozyme-Chitosan Conjugate for Tunable Degradation and Antibacterial Activity.

Hydrogels with controlled degradation and sustained bactericidal activities are promising biomaterial substrates to repair or regenerate the injured tissue. In this work, we present a unique pair of lysozyme and chitosan as a hydrogel that can promote cell growth and proliferation while concomitantly preventing infection during the gradual process of hydrogel degradation and tissue ingrowth. Lysozyme and chitosan containing cell adhesion motifs are chemically modified with photoreactive methacrylate moieties to obtain a crosslinked hydrogel network by visible light irradiation.

Apatite-binding nanoparticulate agonist of hedgehog signaling for bone repair.

The hedgehog signaling pathway plays a critical role in bone development and regeneration. Applications of hedgehog morphogens or small molecular agonists are of interest in bone repair but constrained by low stability, high dose requirement, and nonspecific targeting in vivo. Herein, a nanoparticulate agonist as a new type of hedgehog signaling activator is developed for efficacious bone healing.

Generation of Small RNA-Modulated Exosome Mimetics for Bone Regeneration.

Administration of exosomes is considered an attractive cell-free approach to skeletal repair and pathological disease treatment. However, poor yield for the production technique and unexpected therapeutic efficacy of exosomes have been obstacles to their widespread use in clinical practices. Here, we report an alternative strategy to produce exosome-related vesicles with high yields and improved regenerative capability.

Smoothened agonist sterosome immobilized hybrid scaffold for bone regeneration.

Biomaterial delivery of bioactive agents and manipulation of stem cell fate are an attractive approach to promote tissue regeneration. Here, smoothened agonist sterosome is developed using small-molecule activators [20-hydroxycholesterol (OHC) and purmorphamine (PUR)] of the smoothened protein in the hedgehog pathway as carrier and cargo. Sterosome presents inherent osteoinductive property even without drug loading.

Supramolecular Hydrogels Based on Nanoclay and Guanidine-Rich Chitosan: Injectable and Moldable Osteoinductive Carriers.

Supramolecular hydrogels have great potential as biomaterials for tissue engineering applications or vehicles for delivering therapeutic agents. Herein, a self-healing and pro-osteogenic hydrogel system is developed based on the self-assembly of laponite nanosheets and guanidinylated chitosan, where laponite works as a physical crosslinker with osteoinductive properties to form a network structure with a cationic guanidine group on chitosan chains. The hydrogels can be prepared with varying ratios of chitosan to laponite and display self-healing and injectable properties because of supramolecular forces as well as osteoinductive activity due to nanoclay.

Heparinized chitosan stabilizes the bioactivity of BMP-2 and potentiates the osteogenic efficacy of demineralized bone matrix.

Background: Demineralized bone matrix (DBM), an allograft bone processed to better expose osteoinductive factors such as bone morphogenetic proteins (BMPs), is increasingly used for clinical bone repair. However, more extensive use of DBM is limited by its unpredictable osteoinductivity and low bone formation capacity. Commercial DBM products often employ polymeric carriers to enhance handling properties but such carriers generally do not possess bioactive functions.

Light-controlled reactive oxygen species (ROS)-producible polymeric micelles with simultaneous drug-release triggering and endo/lysosomal escape.

A doxorubicin (DOX)-loaded and light-induced ROS-producing polymeric micelle (D-LRPM), in which light triggers simultaneous DOX-release and endo/lysosomal escape, produces a powerful, spatiotemporally controllable, therapeutic efficacy for tumor treatment.

Photomediated Reactive Oxygen Species-Generable Nanoparticles for Triggered Release and Endo/Lysosomal Escape of Drug upon Attenuated Single Light Irradiation.

Nanoparticles with "smart" stimuli-responsive materials and multiple therapeutic strategies in a single delivery platform have emerged for highly efficient cancer therapy. Here, photomediated reactive oxygen species (ROS)-generable nanoparticles are designed that can trigger drug release and endo/lysosomal escape upon attenuated single light irradiation, simultaneously, for synergistic chemo-photodynamic ablation. In this study, the self-ROS-generable nanoparticles (SRNs) are prepared from the polymer based on polysaccharide, chlorin e6 as ROS generator and lipoic acid as ROS scavenger covalently conjugated pullulan with anticancer drug (doxorubicin, DOX) through self-assembly, and can disassemble via the ROS-mediated reduction of lipoyl group in response to low level exogenous single light switch.