Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin.

The aim of this study was to prepare inclusion nanocomplexes of hyaluronic acid-β-cyclodextrin and simvastatin (HA-β-CD/SIM) and evaluate anti-inflammation effects on lipopolysaccharide (LPS)-activated synoviocytes and chondrogenic differentiation effects on rat adipose-derived stem cells (rADSCs). The β-CD moieties in HA-β-CD could incorporate SIM to form HA-β-CD/SIM nanocomplexes with diameters of 297-350 nm. HA-β-CD/SIM resulted in long-term release of SIM from the nanocomplexes for up to 63 days in a sustained manner.

Biphasic Calcium Phosphate (BCP)-Immobilized Porous Poly (d,l-Lactic-co-Glycolic Acid) Microspheres Enhance Osteogenic Activities of Osteoblasts.

The purpose of this study was to evaluate the potential of porous poly (d,l-lactic--glycolic acid) (PLGA) microspheres (PMSs) immobilized on biphasic calcium phosphate nanoparticles (BCP NPs) (BCP-IM-PMSs) to enhance osteogenic activity. PMSs were fabricated using a fluidic device, and their surfaces were modified with l-lysine (aminated-PMSs), whereas the BCP NPs were modified with heparin⁻dopamine (Hep-DOPA) to obtain heparinized⁻BCP (Hep-BCP) NPs. BCP-IM-PMSs were fabricated via electrostatic interactions between the Hep-BCP NPs and aminated-PMSs.

3D printed alendronate-releasing poly(caprolactone) porous scaffolds enhance osteogenic differentiation and bone formation in rat tibial defects.

The aim of this study was to evaluate the in vitro osteogenic effects and in vivo new bone formation of three-dimensional (3D) printed alendronate (Aln)-releasing poly(caprolactone) (PCL) (Aln/PCL) scaffolds in rat tibial defect models. 3D printed Aln/PCL scaffolds were fabricated via layer-by-layer deposition. The fabricated Aln/PCL scaffolds had high porosity and an interconnected pore structure and showed sustained Aln release.

Ibuprofen-loaded porous microspheres suppressed the progression of monosodium iodoacetate-induced osteoarthritis in a rat model.

The objectives of this study were (1) to fabricate ibuprofen-loaded porous microspheres (IBU/PMSs), (2) to evaluate the in vitro anti-inflammatory effects of the microspheres using LPS-induced inflammation in cultured synoviocytes, and (3) to evaluate the in vivo effect of the IBU/PMSs on the progression of monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in a rat model. A dose-dependent in vitro anti-inflammatory effect on pro-inflammatory cytokine markers (matrix metallopeptidase-3 (MMP-3), matrix metallopeptidase-13 (MMP-13), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5)), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) was observed by confirming with real-time PCR analyses. In vivo, treatment with IBU/PMSs reduced MIA-stimulated mRNA expression of MMP-3, MMP-13, COX-2, ADAMTS-5, IL-6, and TNF-α in rat synoviocytes.

Heparin-immobilized hydroxyapatite nanoparticles as a lactoferrin delivery system for improving osteogenic differentiation of adipose-derived stem cells.

The aim of this study is to fabricate lactoferrin (LF)-carrying hydroxyapatite nanoparticles (HAp NPs) to enhance osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs). HAp NPs were modified with heparin-dopamine (Hep-DOPA) (Hep-HAp) and further immobilized with LF (LF/Hep-HAp). Heparin immobilization on HAp NPs prevented aggregation of HAp NPs in aqueous solution and prolonged the release of LF from LF/Hep-HAp NPs.

The Effect of Alendronate Loaded Biphasic Calcium Phosphate Scaffolds on Bone Regeneration in a Rat Tibial Defect Model.

This study investigated the effect of alendronate (Aln) released from biphasic calcium phosphate (BCP) scaffolds. We evaluated the in vitro osteogenic differentiation of Aln/BCP scaffolds using MG-63 cells and the in vivo bone regenerative capability of Aln/BCP scaffolds using a rat tibial defect model with radiography, micro-computed tomography (CT), and histological examination. In vitro studies included the surface morphology of BCP and Aln-loaded BCP scaffolds visualized using field-emission scanning electron microscope, release kinetics of Aln from BCP scaffolds, alkaline phosphatase (ALP) activity, calcium deposition, and gene expression.

Alendronate-Eluting Biphasic Calcium Phosphate (BCP) Scaffolds Stimulate Osteogenic Differentiation.

Biphasic calcium phosphate (BCP) scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN-) eluting BCP scaffolds.

Improving Osteogenesis Activity on BMP-2-Immobilized PCL Fibers Modified by the γ-Ray Irradiation Technique.

The purpose of this study was to demonstrate the ability of BMP-2-immobilized polycaprolactone (PCL) fibers modified using the γ-ray irradiation technique to induce the osteogenic differentiation of MG-63 cells. Poly acrylic acid (AAc) was grafted onto the PCL fibers by the γ-ray irradiation technique. BMP-2 was then subsequently immobilized onto the AAc-PCL fibers (BMP-2/AAc-PCL).

Osteoblast activity of MG-63 cells is enhanced by growth on a lactoferrin-immobilized titanium substrate.

The aim of this study was to develop a lactoferrin (LF)-immobilized titanium (Ti) substrate to enhance the osteoblast activity of MG-63 cells. Ti substrates were first modified through heparin-dopamine (Hep-DOPA) anchorage. Then, LF was immobilized on the Hep-Ti substrates via electrostatic interactions.

Improving osteoblast functions and bone formation upon BMP-2 immobilization on titanium modified with heparin.

The aim of this study was to develop bone morphogenetic protein-2 (BMP-2) immobilization on titanium (Ti) modified by heparin for improving osteoblast function in vitro and bone formation in vivo. The Ti surface was first modified with heparin and then immobilized with BMP-2 (BMP-2/Hep-Ti). The Ti and modified Ti were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle.

Effect of lactoferrin-impregnated porous poly(lactide-co-glycolide) (PLGA) microspheres on osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs).

The aim of this study was to develop lactoferrin (LF)-impregnated porous poly(lactide-co-glycolide) (PLGA) microspheres (PMs) to induce osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs). Porous PLGA PMs were fabricated by a fluidic device and their surfaces were modified with heparin-dopamine (Hep-DOPA). Then, LF (100μg, 500μg, and 1000μg) was impregnated on the surface of heparinized PMs (Hep-PMs) via electrostatic interactions to yield LF-impregnated PMs.

Bone formation in a rat tibial defect model using carboxymethyl cellulose/BioC/bone morphogenic protein-2 hybrid materials.

The objective of this study was to assess whether carboxymethyl cellulose- (CMC-) based hydrogel containing BioC (biphasic calcium phosphate (BCP); tricalcium phosphate (TCP) : hydroxyapatite (Hap) = 70 : 30) and bone morphogenic protein-2 (BMP-2) led to greater bone formation than CMC-based hydrogel containing BioC without BMP-2. In order to demonstrate bone formation at 4 and 8 weeks, plain radiographs, microcomputed tomography (micro-CT) evaluation, and histological studies were performed after implantation of all hybrid materials on an 8 mm defect of the right tibia in rats. The plain radiographs and micro-CT analyses revealed that CMC/BioC/BMP-2 (0.

The effect of alendronate-loaded polycarprolactone nanofibrous scaffolds on osteogenic differentiation of adipose-derived stem cells in bone tissue regeneration.

The osteogenic effect of culturing adipose-derived stem cells (ADSCs) on alendronate (Aln)-loaded polycarprolactone (PCL) nanofibrous scaffolds was evaluated by examining alkaline phosphatase (ALP) activity, calcium content, and expression of osteogenic differentiation genes in vitro. The 10% Aln/PCL nanofibrous scaffolds showed more ALP activity, mineralization, and osteocalcin and osteopontin mRNA than the 1% or 5% Aln/PCL nanofibrous scaffolds. The capacity of Aln/PCL nanofibrous scaffolds to regenerate new bone was studied in a rat calvarial defect model.

In vitro and in vivo evaluation of bone formation using solid freeform fabrication-based bone morphogenic protein-2 releasing PCL/PLGA scaffolds.

The aim of this study was to develop novel polycaprolactone/poly(lactic-co-glycolic acid) (PCL/PLGA) scaffolds with a heparin-dopamine (Hep-DOPA) conjugate for controlled release of bone morphogenic protein-2 (BMP-2) to enhance osteoblast activity in vitro and also bone formation in vivo. PCL/PLGA scaffolds were prepared by a solid freeform fabrication method. The PCL/PLGA scaffolds were functionalized with Hep-DOPA and then BMP-2 was sequentially coated onto the Hep-DOPA/PCL/PLGA scaffolds.

Osteogenesis induction of periodontal ligament cells onto bone morphogenic protein-2 immobilized PCL fibers.

The purpose of this study was to develop bone morphogenic protein-2 (BMP-2) immobilized PCL fibers to induce osteogenic differentiation of periodontal ligament cells (PDLCs). The PCL fiber surface was modified with heparin-dopamine (Hep-DOPA) (Hep-PCL) and further immobilized with BMP-2 (BMP-2/Hep-PCL). PCL fibers and surface-modified PCL fibers (Hep-PCL and BMP-2/Hep-PCL) were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle.

The effect of titanium with heparin/BMP-2 complex for improving osteoblast activity.

The objective of this study was to investigate the enhanced osteoblast activity of MG-63 cells cultured on titanium (Ti) with a heparin/BMP-2 (Hep/BMP-2) complex. The Ti substrates were initially modified by chemical grafting poly-L-lysine (PLL) using condensing agent, followed by immobilizing the heparin/BMP-2 complex to the PLL-grafted Ti substrate via electrostatic interactions. The surface modification of Ti substrates with PLL and/or Hep/BMP-2 complex were confirmed with scanning electron microscopy, contact angle measurements, and X-ray photoelectron spectroscopy.

Bone formation of middle ear cavity using biphasic calcium phosphate lyophilized with Escherichia coli-derived recombinant human bone morphogenetic protein 2 using animal model.

Objective: The aim of the study was to analyze the value of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) coated biphasic calcium phosphate (BCP) for the obliteration of middle ear bone defect after mastoid surgery.

Methods: Twenty-four specific pathogen-free Sprague-Dawley rats were randomly assigned to the BCP group (n=12) and BCP-ErhBMP-2 group (n=12; in which BCP scaffold of the granular type was coated with ErhBMP-2). In both groups, BCP scaffold was used to surgically fill the middle ear bulla.

Co-delivery of platelet-derived growth factor (PDGF-BB) and bone morphogenic protein (BMP-2) coated onto heparinized titanium for improving osteoblast function and osteointegration.

The aim of this study was to improve osteoblast function by delivering two growth factors, PDGF-BB and BMP-2, incorporated onto heparinized titanium (Hep-Ti) substrate. To achieve co-delivery of PDGF-BB and BMP-2, the surface of anodized Ti was immobilized with heparin, and then the two growth factors were coated onto the Hep-Ti surface. Incorporation of the two growth factors onto Hep-Ti was evaluated by SEM and XPS.

Local delivery of alendronate eluting chitosan scaffold can effectively increase osteoblast functions and inhibit osteoclast differentiation.

The aim of this study was to investigate the effect of alendronate released from chitosan scaffolds on enhancement of osteoblast functions and inhibition of osteoclast differentiation in vitro. The surface and cell morphologies of chitosan scaffolds and alendronate-loaded chitosan scaffolds were characterized by variable pressure field emission scanning electron microscope (VP-FE-SEM). Alendronate was released in a sustained manner.

Gentamicin and bone morphogenic protein-2 (BMP-2)-delivering heparinized-titanium implant with enhanced antibacterial activity and osteointegration.

Insufficient bonding of implants to bone tissues and bacterial infections lead to the failure of titanium (Ti)-based orthopedic and dental implants. The aim of this study is to develop novel Ti implants that enhance osteoblast functions, while simultaneously decreasing bacterial infections. First, the surface of pristine Ti was functionalized with heparin-dopamine by mimicking a mussel adhesion mechanism.

The effect of bone morphogenic protein-2-coated tri-calcium phosphate/hydroxyapatite on new bone formation in a rat model of femoral distraction osteogenesis.

Background Aims: Distraction osteogenesis (DO) is an increasingly popular technique used to stimulate new bone formation to treat orthopedic disorders resulting from bone defects and deficits. Because of various possible complications that can occur during the long consolidation period, the development of procedures to accelerate regenerated ossification is clearly desirable. The purpose of this study was to evaluate the effect of single insertions of bone morphogenic protein-2 (BMP-2), delivered by tri-calcium phosphate (TCP)/hydroxyapatite (HA), administered at osteotomy sites, on the rate of new bone formation during DO in a rat model.

Effect of heparin and alendronate coating on titanium surfaces on inhibition of osteoclast and enhancement of osteoblast function.

The failure of orthopedic and dental implants has been attributed mainly to loosening of the implant from host bone, which may be due to weak bonding of the implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic and dental implants because of its excellent biocompatibility and outstanding mechanical properties. Therefore, in the field of materials science and tissue engineering, there has been extensive research to immobilize bioactive molecules on the surface of implant materials in order to provide the implants with improved adhesion to the host bone tissue.

Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species.

Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation.

The effect of immobilization of heparin and bone morphogenic protein-2 (BMP-2) to titanium surfaces on inflammation and osteoblast function.

The aim of this study was to investigate biologic function of bone morphorgenic protein-2 (rhBMP-2) immobilized on the heparin-grafted Ti surface. Ti surfaces were first modified by 3-aminopropyltriethoxysilane (ATPES), followed by grafting of heparin. BMP-2 was then immobilized on the heparin-grafted Ti surfaces.