Biomimetic Bone-Like Composite Hydrogel Scaffolds Composed of Collagen Fibrils and Natural Hydroxyapatite for Promoting Bone Repair.

Bone is a complex organic-inorganic composite tissue composed of ∼30% organics and ∼70% hydroxyapatite (HAp). Inspired by this, we used 30% collagen and 70% HAp extracted from natural bone using the calcination method to generate a biomimetic bone composite hydrogel scaffold (BBCHS). In one respect, BBCHS, with a fixed proportion of inorganic and organic components similar to natural bone, exhibits good physical properties. In another respect, the highly biologically active and biocompatible HAp from natural bone effectively promotes osteogenic differentiation, and type I collagen facilitates cell adhesion and spreading. Additionally, the well-structured porosity of the BBCHS provides sufficient growth space for bone marrow mesenchymal stem cells (BMSCs) while promoting substance exchange. Compared to the control group, the new bone surface of the defective location in the B-HA70+Col group is increased by 3.4-fold after 8 weeks of in vivo experiments. This strategy enables the BBCHS to closely imitate the chemical makeup and physical structure of natural bone. With its robust biocompatibility and osteogenic activity, the BBCHS can be easily adapted for a wide range of bone repair applications and offers promising potential for future research and development.

Multifunctional nanomaterials via cell cuproptosis and oxidative stress for treating osteosarcoma and OS-induced bone destruction.

Reactive Oxygen Species (ROS) refers to a highly reactive class of oxidizing species that have the potential to induce cellular apoptosis and necrosis. Cuproptosis, a type of cell death, is primarily associated with the effects of copper ions. However, the specific relationship between ROS, cuproptosis, and osteosarcoma (OS) remains relatively unexplored. Additionally, there is limited research on the use of cuproptosis in conjunction with oxidative stress for treating OS and inhibiting tumor-induced bone destruction. To address these gaps, a novel treatment approach has been developed for OS and neoplastic bone destruction. This approach involves the utilization of glutathione (GSH) and pH-responsive organic-inorganic mesoporous silica nanoparticles@Cu2S@oxidized Dextran (short for MCD). The MCD material demonstrates excellent cytocompatibility, osteogenesis, tumor suppression, and the ability to inhibit osteoclast formation. The specific mechanism of action involves the mitochondria of the MCD material inhibiting key proteins in the tricarboxylic acid (TCA) cycle. Simultaneously, the generation of ROS promotes this inhibition and leads to alterations in cellular energy metabolism. Moreover, the MCD biomaterial exhibits promising mild-temperature photothermal therapy in the second near-infrared (NIR-II) range, effectively mitigating tumor growth and OS-induced bone destruction in vivo.

The transformation of multifunctional bio-patch to hydrogel on skin wounds for efficient scarless wound healing.

Hydrogels have been widely used in various biomedical applications, including skin regeneration and tissue repair. However, the capability of certain hydrogels to absorb exudate or blood from surrounding wounds, coupled with the challenge in their long-term storage to prevent bacterial growth, can pose limitations to their efficacy in biological applications. To address these challenges, the development of a multifunctional aloin-arginine-alginate (short for 3A) bio-patch capable of transforming into a hydrogel upon absorbing exudate or blood from neighboring wounds for cutaneous regeneration is proposed. The 3A bio-patch exhibits outstanding features, including an excellent porous structure, swelling properties, and biodegradability. These characteristics allow for the rapid absorption of wound exudates and subsequent transformation into a hydrogel that is suitable for treating skin wounds. Furthermore, the 3A bio-patch exhibits remarkable antibacterial and anti-inflammatory properties, leading to accelerated wound healing and scarless repair in vivo. This study presents a novel approach to the development of cutaneous wound dressing materials.

A nano-conductive osteogenic hydrogel to locally promote calcium influx for electro-inspired bone defect regeneration.

Conductive nano-materials and electrical stimulation (ES) have been recognized as a synergetic therapy for ordinary excitable tissue repair. It is worth noting that hard tissues, such as bone tissue, possess bioelectrical properties as well. However, insufficient attention is paid to the synergetic therapy for bone defect regeneration via conductive biomaterials with ES. Here, a novel nano-conductive hydrogel comprising calcium phosphate-PEDOT:PSS-magnesium titanate-methacrylated alginate (CPM@MA) was synthesized for electro-inspired bone tissue regeneration. The nano-conductive CPM@MA hydrogel has demonstrated excellent electroactivity, biocompatibility, and osteoinductivity. Additionally, it has the potential to enhance cellular functionality by increasing endogenous transforming growth factor-beta1 (TGF-ß1) and activating TGF-ß/Smad2 signaling pathway. The synergetic therapy could facilitate intracellular calcium enrichment, resulting in a 5.8-fold increase in calcium concentration compared to the control group in the CPM@MA ES + group. The nano-conductive CPM@MA hydrogel with ES could significantly promote electro-inspired bone defect regeneration in vivo, uniquely allowing a full repair of rat femoral defect within 4 weeks histologically and mechanically. These results demonstrate that our synergistic strategy effectively promotes bone restoration, thereby offering potential advancements in the field of electro-inspired hard tissue regeneration using novel nano-materials with ES.

Synergistic Effect of Magneto-Mechanical Bioengineered Stem Cells and Magnetic Field to Alleviate Osteoporosis.

Therapeutic bioengineering based on stem cell therapy holds great promise in biomedical applications. However, the application of this treatment is limited in orthopedics because of their poor survival, weak localization, and low cell retention. In this work, magneto-mechanical bioengineered cells consisting of magnetic silica nanoparticles (MSNPs) and mesenchymal stem cells (MSCs) are prepared to alleviate osteoporosis. The magneto-mechanical bioengineered MSCs with spatial localization, cell retention, and directional tracking capabilities could be mediated by a guided magnetic field (MF) in vitro and in vivo. Furthermore, high uptake rates of the MSNPs ensure the efficient construction of magnetically controlled MSCs within 2 h. In conjunction with external MF, the magneto-mechanical bioengineered MSCs have the potential for the activation of the YAP/ß-catenin signaling pathway, which could further promote osteogenesis, mineralization, and angiogenesis. The synergistic effects of MSNPs and guided MF could also decline bone resorption to rebalance bone metabolism in bone loss diseases. In vivo experiments confirm that the functional MSCs and guided MF could effectively alleviate postmenopausal osteoporosis, and the bone mass of the treated osteoporotic bones by using the bioengineered cells for 6 weeks is nearly identical to that of the healthy ones. Our results provide a new avenue for osteoporosis management and treatment, which contribute to the future advancement of magneto-mechanical bioengineering and treatment.