Bioactive Scaffold Fabricated by 3D Printing for Enhancing Osteoporotic Bone Regeneration.

We develop a poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP)-based scaffold through a three-dimensional (3D) printing technique incorporating icaritin (ICT), a unique phytomolecule, and secretome derived from human fetal mesenchymal stem cells (HFS), to provide mechanical support and biological cues for stimulating bone defect healing. With the sustained release of ICT and HFS from the composite scaffold, the cell-free scaffold efficiently facilitates the migration of MSCs and promotes bone regeneration at the femoral defect site in the ovariectomy (OVX)-induced osteoporotic rat model. Furthermore, mechanism study results indicate that the combination of ICT and HFS additively activates the Integrin-FAK (focal adhesion kinase)-ERK1/2 (extracellular signal-regulated kinase 1/2)-Runx2 (Runt-related transcription factor 2) axis, which could be linked to the beneficial recruitment of MSCs to the implant and subsequent osteogenesis enhancement.

Biosynthesized Bandages Carrying Magnesium Oxide Nanoparticles Induce Cortical Bone Formation by Modulating Endogenous Periosteal Cells.

Bone grafting is frequently conducted to treat bone defects caused by trauma and tumor removal, yet with significant medical and socioeconomic burdens. Space-occupying bone substitutes remain challenging in the control of osteointegration, and meanwhile activation of endogenous periosteal cells by using non-space-occupying implants to promote new bone formation becomes another therapeutic strategy. Here, we fabricated a magnesium-based artificial bandage with optimal micropatterns for activating periosteum-associated biomineralization.

Interactive effects of cerium and copper to tune the microstructure of silicocarnotite bioceramics towards enhanced bioactivity and good biosafety.

Endowing biomaterials with functional elements enhances their biological properties effectively. However, improving bioactivity and biosafety simultaneously is still highly desirable. Herein, cerium (Ce) and copper (Cu) are incorporated into silicocarnotite (CPS) to modulate the constitution and microstructure for degradability, bioactivity and biosafety regulation.

Magnesium-Encapsulated Injectable Hydrogel and 3D-Engineered Polycaprolactone Conduit Facilitate Peripheral Nerve Regeneration.

Peripheral nerve injury is a challenging orthopedic condition that can be treated by autograft transplantation, a gold standard treatment in the current clinical setting. Nevertheless, limited availability of autografts and potential morbidities in donors hampers its widespread application. Bioactive scaffold-based tissue engineering is a promising strategy to promote nerve regeneration.

Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis.

Epididymal white adipose tissue (eWAT) secretes an array of cytokines to regulate the metabolism of organs and tissues in high-fat diet (HFD)-induced obesity, but its effects on bone metabolism are not well understood. Here, we report that macrophages in eWAT are a main source of osteopontin, which selectively circulates to the bone marrow and promotes the degradation of the bone matrix by activating osteoclasts, as well as modulating bone marrow-derived macrophages (BMDMs) to engulf the lipid droplets released from adipocytes in the bone marrow of mice. However, the lactate accumulation induced by osteopontin regulation blocks both lipolysis and osteoclastogenesis in BMDMs by limiting the energy regeneration by ATP6V0d2 in lysosomes.

Biodegradable magnesium pins enhanced the healing of transverse patellar fracture in rabbits.

Displaced fractures of patella often require open reduction surgery and internal fixation to restore the extensor continuity and articular congruity. Fracture fixation with biodegradable magnesium (Mg) pins enhanced fracture healing. We hypothesized that fixation with Mg pins and their degradation over time would enhance healing of patellar fracture radiologically, mechanically, and histologically.

Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss.

Introduction: Magnesium (Mg) has a prophylactic potential against the onset of hyperlipidemia. Similar to statin, Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass. The combination of statin with Mg ions (Mg) may be able to alleviate the high-fat diet (HFD)-induced bone loss and reduce the side-effects of statin.

Calcitonin Gene-Related Peptide Enhances Distraction Osteogenesis by Increasing Angiogenesis.

Distraction osteogenesis (DO) is a well-established surgical technique for treating bone defect and limb lengthening. The major drawback of DO is the long treatment period as the external fixator has to be kept in place until consolidation is completed. Calcitonin gene-related peptide (CGRP) has been reported to promote angiogenesis by affecting endothelial progenitor cells (EPCs) in limb ischemia and wound healing.

Biodegradable Magnesium-Based Implants in Orthopedics-A General Review and Perspectives.

Biodegradable Mg-based metals may be promising orthopedic implants for treating challenging bone diseases, attributed to their desirable mechanical and osteopromotive properties. This Review summarizes the current status and future research trends for Mg-based orthopedic implants. First, the properties between Mg-based implants and traditional orthopedic implants are compared on the following aspects: in vitro and in vivo degradation mechanisms of Mg-based implants, peri-implant bone responses, the fate of the degradation products, and the cellular and molecular mechanisms underlying the beneficial effects of Mg ions on osteogenesis.

Wnt16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade.

Objectives: Wnt16 is implicated in bone fracture and bone mass accrual both in animals and humans. However, its functional roles and molecular mechanism in chondrocyte differentiation and osteoarthritis (OA) pathophysiology remain largely undefined. In this study, we analysed its mechanistic association and functional relationship in OA progression in chondrocyte lineage.

A bone-targeting delivery system carrying osteogenic phytomolecule icaritin prevents osteoporosis in mice.

Targeting delivery system has been widely used in packaging drugs for medical therapies attributed to its high efficiency and efficacy. A Traditional Chinese Medicine (TCM) formula consisting of Herba Epimedii has previously been shown to effectively treat postmenopausal osteoporosis. We have subsequently found that icaritin, which was a flavonoid isolated from both Herba Epimedii and its serum metabolites after oral administration, inhibited the adipogenic capacity of bone mesenchymal stem cells (BMSCs) while promoted their osteogenesis.

An innovative Mg/Ti hybrid fixation system developed for fracture fixation and healing enhancement at load-bearing skeletal site.

Magnesium (Mg) is a potential biomaterial suitable for developing biodegradable orthopaedic implants, especially as internal fixators for fracture fixation at non-load bearing skeletal sites. However, Mg alone cannot provide sufficient mechanical support for stable fracture fixation at load bearing sites due to its rapid degradation in the early stage after implantation. In consideration of the strengths and weaknesses of Mg, we developed an innovative magnesium/titanium (Mg/Ti) hybrid fixation system for long bone fracture fixation and investigated the fixation efficacy.

Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats.

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG).

Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength of Intact Bones in Adult Male Rats.

We investigated the systemic effect of sclerostin monoclonal antibody (Scl-Ab) treatment on intact non-operated bones in an open osteotomy male Sprague Dawley (SD) rat model. Six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were injected subcutaneously with vehicle or Scl-Ab (25 mg/kg, 2 times per week) treatment for 9 weeks.

Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits.

Vascular hyperpermeability and highly upregulated bone resorption in the destructive repair progress of steroid-associated osteonecrosis (SAON) are associated with a high expression of VEGF and high Src activity (Src is encoded by the cellular sarcoma [c-src] gene). This study was designed to prove our hypothesis that blocking the VEGF-Src signaling pathway by specific Src siRNA is able to prevent destructive repair in a SAON rabbit model. Destructive repair in SAON was induced in rabbits.

A Comparative Study on the Biomechanical and Histological Properties of Bone-to-Bone, Bone-to-Tendon, and Tendon-to-Tendon Healing: An Achilles Tendon-Calcaneus Model in Goats.

Background: Surgical repair around the bone-tendon insertion (BTI) may involve bone-to-bone (BB), bone-to-tendon (BT), or tendon-to-tendon (TT) reattachment with varying healing outcome.

Hypothesis: The repair of Achilles tendon-calcaneus (ATC) by reattachment of homogeneous tissue (BB or TT) would heal faster, with respect to tensile properties at the healing complex, than those of reattachment of heterogeneous tissues (BT) over time.

Study Design: Controlled laboratory study.

Sclerostin monoclonal antibody enhanced bone fracture healing in an open osteotomy model in rats.

Sclerostin is a negative regulator of bone formation. Sclerostin monoclonal antibody (Scl-Ab) treatment promoted bone healing in various animal models. To further evaluate the healing efficiency of Scl-Ab in osteotomy healing, we investigated the time course effects of systemic administration of Scl-Ab on fracture repair in rat femoral osteotomy model.

Extracorporeal shockwave enhanced regeneration of fibrocartilage in a delayed tendon-bone insertion repair model.

Fibrous tissue is often formed in delayed healing of tendon bone insertion (TBI) instead of fibrocartilage. Extracorporeal shockwave (ESW) provides mechanical cues and upregulates expression of fibrocartilage-related makers and cytokines. We hypothesized that ESW would accelerate fibrocartilage regeneration at the healing interface in a delayed TBI healing model.

Extracorporeal shockwave therapy for treatment of delayed tendon-bone insertion healing in a rabbit model: a dose-response study.

Background: Tendon-bone insertion (TBI) consists of both hard and soft tissues. TBI injury with delayed repair is not uncommon. High-dose extracorporeal shockwave (ESW) is effective for treating nonunion fracture, whereas low-dose ESW is used for tendinopathy therapy.

Low-magnitude high-frequency vibration (LMHFV) enhances bone remodeling in osteoporotic rat femoral fracture healing.

Low-magnitude high-frequency vibration (LMHFV) (35 Hz, 0.3 g) accelerates fracture healing by enhancing callus formation and mineralization for both normal and osteoporotic rats in our previous studies.1,2 We hypothesized that LMHFV enhances fracture healing through bone remodeling.