Mechanoregulation analysis of bone formation in tissue engineered constructs requires a volumetric method using time-lapsed micro-computed tomography.

Bone can adapt its microstructure to mechanical loads through mechanoregulation of the (re)modeling process. This process has been investigated in vivo using time-lapsed micro-computed tomography (micro-CT) and micro-finite element (FE) analysis using surface-based methods, which are highly influenced by surface curvature. Consequently, when trying to investigate mechanoregulation in tissue engineered bone constructs, their concave surfaces make the detection of mechanoregulation impossible when using surface-based methods.

Physiological cell bioprinting density in human bone-derived cell-laden scaffolds enhances matrix mineralization rate and stiffness under dynamic loading.

Human organotypic bone models are an emerging technology that replicate bone physiology and mechanobiology for comprehensive experimentation over prolonged periods of time. Recently, we introduced a mineralized bone model based on 3D bioprinted cell-laden alginate-gelatin-graphene oxide hydrogels cultured under dynamic loading using commercially available human mesenchymal stem cells. In the present study, we created cell-laden scaffolds from primary human osteoblasts isolated from surgical waste material and investigated the effects of a previously reported optimal cell printing density (5 × 10 cells/mL bioink) vs.

Bioactive Interpenetrating Hydrogel Networks Based on 2-Hydroxyethyl Methacrylate and Gelatin Intertwined with Alginate and Dopped with Apatite as Scaffolding Biomaterials.

Our goal was to create bioimitated scaffolding materials for biomedical purposes. The guiding idea was that we used an interpenetrating structural hierarchy of natural extracellular matrix as a "pattern" to design hydrogel scaffolds that show favorable properties for tissue regeneration. Polymeric hydrogel scaffolds are made in a simple, environmentally friendly way without additional functionalization.

Multi-doped apatite: Strontium, magnesium, gallium and zinc ions synergistically affect osteogenic stimulation in human mesenchymal cells important for bone tissue engineering.

Functional calcium phosphate biomaterials can be designed as carriers of a balanced mixture of biologically relevant ions able to target critical processes in bone regeneration. They hold the potential to use mechanisms very similar to growth factors naturally produced during fracture healing, while circumventing some of their drawbacks. Here we present a novel phase of carbonated-apatite containing Mg, Sr, Zn and Ga ions (HApMgSrZnGa).

Long-term mechanical loading is required for the formation of 3D bioprinted functional osteocyte bone organoids.

Mechanical loading has been shown to influence various osteogenic responses of bone-derived cells and bone formation. However, the influence of mechanical stimulation on the formation of bone organoidis not clearly understood. Here, three-dimensional (3D) bioprinted human mesenchymal stem cells-laden graphene oxide composite scaffolds were cultured in a novel cyclic-loading bioreactors for up to 56 d.

Biodegradable Hydrogel Scaffolds Based on 2-Hydroxyethyl Methacrylate, Gelatin, Poly(β-amino esters), and Hydroxyapatite.

New composite 3D scaffolds were developed as a combination of synthetic polymer, poly(2-hydroxyethyl methacrylate) (PHEMA), and a natural polymer, gelatin, with a ceramic component, nanohydroxyapatite (ID nHAp) dopped with metal ions. The combination of a synthetic polymer, to be able to tune the structure and the physicochemical and mechanical properties, and a natural polymer, to ensure the specific biological functions of the scaffold, with inorganic filler was applied. The goal was to make a new material with superior properties for applications in the biomedical field which mimics as closely as possible the native bone extracellular matrix (ECM).

3D Bioprinting of Human Tissues: Biofabrication, Bioinks, and Bioreactors.

The field of tissue engineering has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes for regenerative medicine and pharmaceutical research. Conventional scaffold-based approaches are limited in their capacity to produce constructs with the functionality and complexity of native tissue. Three-dimensional (3D) bioprinting offers exciting prospects for scaffolds fabrication, as it allows precise placement of cells, biochemical factors, and biomaterials in a layer-by-layer process.

Time-lapsed imaging of nanocomposite scaffolds reveals increased bone formation in dynamic compression bioreactors.

Progress in bone scaffold development relies on cost-intensive and hardly scalable animal studies. In contrast to in vivo, in vitro studies are often conducted in the absence of dynamic compression. Here, we present an in vitro dynamic compression bioreactor approach to monitor bone formation in scaffolds under cyclic loading.

3D bioprinting of graphene oxide-incorporated cell-laden bone mimicking scaffolds for promoting scaffold fidelity, osteogenic differentiation and mineralization.

Bioprinting is a promising technique for facilitating the fabrication of engineered bone tissues for patient-specific defect repair and for developing in vitro tissue/organ models for ex vivo tests. However, polymer-based ink materials often result in insufficient mechanical strength, low scaffold fidelity and loss of osteogenesis induction because of the intrinsic swelling/shrinking and bioinert properties of most polymeric hydrogels. Here, we developed a human mesenchymal stem cells (hMSCs)-laden graphene oxide (GO)/alginate/gelatin composite bioink to form 3D bone-mimicking scaffolds using a 3D bioprinting technique.

Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures.

Cells sense and respond to scaffold pore geometry and mechanical stimuli. Many fabrication methods used in bone tissue engineering render structures with poorly controlled pore geometries. Given that cell-scaffold interactions are complex, drawing a conclusion on how cells sense and respond to uncontrolled scaffold features under mechanical loading is difficult.

Optimization of mechanical stiffness and cell density of 3D bioprinted cell-laden scaffolds improves extracellular matrix mineralization and cellular organization for bone tissue engineering.

Bioprinting is an emerging technology in which cell-laden biomaterials are precisely dispersed to engineer artificial tissues that mimic aspects of the anatomical and structural complexity of relatively soft tissues such as skin, vessels, and cartilage. However, reproducing the highly mineralized and cellular diversity of bone tissue is still not easily achievable and is yet to be demonstrated. Here, an extrusion-based 3D bioprinting strategy is utilized to fabricate 3D bone-like tissue constructs containing osteogenic cellular organization.

Alginate dependent changes of physical properties in 3D bioprinted cell-laden porous scaffolds affect cell viability and cell morphology.

Three-dimensional (3D) cell-laden scaffolds are becoming more prevalent in bone tissue repair and regeneration. However, the influence of physical scaffold properties on cell behavior is still unclear. In this study, we fabricated four different alginate concentration (0.

hiPS-MSCs differentiation towards fibroblasts on a 3D ECM mimicking scaffold.

Fibroblasts are ubiquitous cells that constitute the stroma of virtually all tissues and play vital roles in homeostasis. The poor innate healing capacity of fibroblastic tissues is attributed to the scarcity of fibroblasts as collagen-producing cells. In this study, we have developed a functional ECM mimicking scaffold that is capable to supply spatial allocation of stem cells as well as anchorage and storage of growth factors (GFs) to direct stem cells differentiate towards fibroblasts.

Electrospun PCL/PEO coaxial fibers for basic fibroblast growth factor delivery.

The poor innate healing capacity of fibroblastic tissues, such as pelvic floor fascia, is attributed to the scarcity of fibroblasts to produce collagen, as the main collagen producing cells. Coaxial electrospun PCL/PEO fibers containing basic fibroblast growth factor (FGF-2) were evaluated for the local and temporal delivery of FGF-2 for promoting fibroblast proliferation. PCL/PEO coaxial fibers with a highly porous surface were successfully developed using coaxial electrospinning.

Cathodic Polarization Coats Titanium Based Implant Materials with Enamel Matrix Derivate (EMD).

The idea of a bioactive surface coating that enhances bone healing and bone growth is a strong focus of on-going research for bone implant materials. Enamel matrix derivate (EMD) is well documented to support bone regeneration and activates growth of mesenchymal tissues. Thus, it is a prime candidate for coating of existing implant surfaces.

Ultraporous interweaving electrospun microfibers from PCL-PEO binary blends and their inflammatory responses.

Production of one dimensional nanomaterials with secondary morphology exhibiting unique functions is challenging. Here we report for the first time that a nanoscale immiscible polymer blend solution electrojet can assemble into ultraporous interweaving microfibers. This intriguingly novel morphology originated from a blend of polycaprolactone (PCL) and polyethylene oxide (PEO) in a DCM-DMF mixed solution when the ratio between each component reached a threshold and when the electrospinning parameters were delicately controlled.

Effect of proline-rich synthetic peptide-coated titanium implants on bone healing in a rabbit model.

Purpose: Previous studies have demonstrated the capacity of a designed proline-rich synthetic peptide to stimulate osteoblast differentiation and biomineralization in vitro. Therefore, the aim of the present study was to evaluate the osseointegration capacity of titanium (Ti) implants coated with these peptides in a rabbit model.

Materials And Methods: Four calibrated defects were prepared in the tibiae of three New Zealand rabbits, and the defects were randomized into a test group (peptide-modified machined Ti implant) and a control group (unmodified machined Ti implant).

Coating of metal implant materials with strontium.

The aim of this study was to show that cathodic polarization can be used for coating commercial implant surfaces with an immobilized but functional and bioavailable surface layer of strontium (Sr). Moreover, this study assessed the effect of fluorine on Sr-attachment. X-ray photoelectron spectroscopy revealed that addition of fluorine (F) to the buffer during coating increased surface Sr-amounts but also changed the chemical surface composition by adding SrF2 alongside of SrO whereas pre-treatment of the surface by pickling in hydrofluoric acid appeared to hinder Sr-attachment.

Simvastatin-activated implant surface promotes osteoblast differentiation in vitro.

The bone growth promoting effects of statins suggest that these bioactive molecules can be used to improve the integration of bone-anchored implants. This study aimed at the application of simvastatin with dental implants for use in patients with low bone density. Coin-shaped titanium zirconium samples with grit-blasted and acid-etched surface were coated with simvastatin, using a novel anodic oxidation setup under alkaline conditions.

Porous ceramic titanium dioxide scaffolds promote bone formation in rabbit peri-implant cortical defect model.

Titanium oxide (TiO₂) scaffolds have previously been reported to exhibit very low mechanical strength. However, we have been able to produce a scaffold that features a high interconnectivity, a porosity of 91% and a compressive strength above 1.2 MPa.

Effect of enamel matrix derivative and of proline-rich synthetic peptides on the differentiation of human mesenchymal stem cells toward the osteogenic lineage.

With the aim of discovering new molecules for induction of bone formation and biomineralization, combination of bioinformatics and simulation methods were used to design the structure of artificial peptides based on proline-rich domains of enamel matrix proteins. In this study, the effect of such peptides on the differentiation toward the osteogenic lineage of human umbilical cord mesenchymal stem cells (hUCMSCs) was evaluated with or without osteogenic supplements (hydrocortisone, β-glycerol phosphate, and ascorbic acid) and compared to the effect of the commercially available enamel matrix derivative (EMD). It was hypothesized that the differentiation toward the osteogenic lineage of hUCMSCs would be promoted by the treatment with the synthetic peptides when combined with differentiation media, or it could even be directed exclusively by the synthetic peptides.

Decreased bone mineral density and reduced bone quality in H(+) /K(+) ATPase beta-subunit deficient mice.

Proton pump inhibitors (PPIs) are widely used against gastroesophageal reflux disease. Recent epidemiological studies suggest that PPI users have an increased risk of fractures, but a causal relationship has been questioned. We have therefore investigated the skeletal phenotype in H(+) /K(+) ATPase beta-subunit knockout (KO) female mice.

In vivo performance of titanium implants functionalized with eicosapentaenoic acid and UV irradiation.

The aim of this study was to design implant surfaces that attach less to bone but at the same time improve osseous healing for use as temporary bone fracture plates. The strategy was to combine the nonadhesive properties of smooth titanium (Ti) surfaces with the differentiative and anti-inflammatory properties of eicosapentaenoic acid (EPA). Machined Ti implant surfaces coated with a layer of EPA, with or without UV irradiation, were characterized by X-ray photoelectron spectroscopy, and their in vivo performance was evaluated in New Zealand White rabbits.

Rosuvastatin promotes osteoblast differentiation and regulates SLCO1A1 transporter gene expression in MC3T3-E1 cells.

Rosuvastatin (RSV) is a synthetic statin with favourable pharmacologic properties including minimal metabolism, hepatic selectivity and enhanced inhibition of HMG-CoA reductase. An induction of osteoblast differentiation has been reported in vitro with lipophilic statins but not with RSV, which, like pravastatin, is relatively hydrophilic compared with other statins. To mediate its action, an active transport mechanism via solute carrier (SLC) transporters from the SLC16, SLC21/SLCO and SLC22 gene family - specifically Slc16a1, Slco1a1, Slco2b1 and Slc22a8 - may be present to allow effective entry in osteoblastic cells.