Bone Regenerative Properties Research Articles

3D printed mesoporous bioactive glass, bioglass 45S5, and β-TCP scaffolds for regenerative medicine: A comparative invitro study.

While autografts to date remain the "gold standard" for bone void fillers, synthetic bone grafts have garnered attention due to their favorable advantages such as ability to be tailored in terms of their physical and chemical properties. Bioactive glass (BG), an inorganic material, has the capacity to form a strong bond with bone by forming a bone-like apatite surface, enhancing osteogenesis. Coupled with additive manufacturing (3D printing) it is possible to maximize bone regenerative properties of the BG. The objective of this study was to synthesize and characterize 3D printed mesoporous bioactive glass (MBG), BG 45S5, and compare to β-Tricalcium phosphate (β-TCP) based scaffolds; test cell viability and osteogenic differentiation on human osteoprogenitor cells invitro. MBG, BG 45S5, and β-TCP were fabricated into colloidal gel suspensions, tested with a rheometer, and manufactured into scaffolds using a 3D direct-write micro-printer. The materials were characterized in terms of microstructure and composition with Thermogravimetric Analyzer/Differential Scanning Calorimeter (TGA/DSC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Micro-Computed Tomography (μ-CT), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Mattauch-Herzog-Inductively Coupled Plasma-Mass Spectrometry (MH-ICP-MS). Scaffolds were tested for cell proliferation and osteogenic differentiation using human osteoprogenitor cells. Osteogenic media was used for differentiation, and immunocytochemistry for osteogenic markers Runx-2, Collagen-I, and Osteocalcin. The cell viability results after 7 days of culture yielded significantly higher (p < 0.05) results in β-TCP scaffolds compared to BG 45S5 and MBG groups. All materials expressed osteogenic markers after 21 days of culture in expansion and osteogenic media.

Toward Smart Biomimetic Apatite-Based Bone Scaffolds with Spatially Controlled Ion Substitutions.

Biomimetic apatites exhibit a high reactivity allowing ion substitutions to modulate their in vivo response. We developed a novel approach combining several bioactive ions in a spatially controlled way in view of subsequent releases to address the sequence of events occurring after implantation, including potential microorganisms' colonization. Innovative micron-sized core-shell particles were designed with an external shell enriched with an antibacterial ion and an internal core substituted with a pro-angiogenic or osteogenic ion. After developing the proof of concept, two ions were particularly considered, Ag+ in the outer shell and Cu2+ in the inner core. In vitro evaluations confirmed the cytocompatibility through Ag-/Cu-substituting and the antibacterial properties provided by Ag+. Then, these multifunctional "smart" particles were embedded in a polymeric matrix by freeze-casting to prepare 3D porous scaffolds for bone engineering. This approach envisions the development of a new generation of scaffolds with tailored sequential properties for optimal bone regeneration.

The role of PIWI-interacting RNA in naringin pro-angiogenesis by targeting HUVECs

Angiogenesis is a biological process in which resting endothelial cells start proliferating, migrating and forming new blood vessels. Angiogenesis is particularly important in the repair of bone tissue defects. Naringin (NG) is the main active monomeric component of traditional Chinese medicine, which has various biological activities, such as anti-osteoporosis, anti-inflammatory, blood activation and microcirculation improvement. At present, the mechanism of naringin in the process of angiogenesis is not clear. PIWI protein-interacting RNA (piRNA) is a small noncoding RNA (sncRNA) that has the functions of regulating protein synthesis, regulating the structure of chromatin and the genome, stabilizing mRNA and others. Several studies have demonstrated that piRNAs can mediate the angiogenesis process. Whether naringin can interfere with the process of angiogenesis by regulating piRNAs and related target genes deserves further exploration. Thus, the purpose of this study was to validate the potential angiogenic and bone regeneration properties and related mechanisms of naringin both in vivo and in vitro.

Integrated osteoimmunomodulatory strategies based on designing scaffold surface properties in bone regeneration.

Those who have used traditional biomaterials as bone substitutes have always regarded the immune response as an obstacle leading to implant failure. However, cumulative evidence revealed that blindly minimizing host immune reactions cannot induce successful bone regeneration. With the emergence of the new concept of osteoimmunology, the intimate mutual effects between the skeletal system and the immune system have been gradually recognized, promoting the innovation of biomaterials with osteoimmunomodulatory properties. By tuning the surface properties, biomaterials can precisely manipulate the osteoimmune environment favoring bone regeneration. In this review, we first reviewed the mutual effects between the skeletal system and the immune system to show the importance of immunomodulation on bone regeneration. Subsequently, we summarize the recent developments in surface modification strategies in terms of the surface physicochemical properties and surface coatings and explain how these modification strategies work.

Rapid wet chemical synthesis of bioactive glass with high yield by probe sonication.

Bioactive glasses (BGs) are inorganic biomaterials which possess favourable properties for bone repair and regeneration. The biological properties of the BGs depend on their physical features. This manuscript describes a simple methodology for rapid synthesis of BG nanoparticles (NPs) with tailored physical properties using ultrasonic disruption produced by an ultrasonic probe. The ultrasonic probe generates stable and transient cavitation which increases the mass transfer and accelerates the chemical reaction. This approach is relatively green as it evades the use of the drastic acidic conditions required for hydrolysis. The prepared BG NPs were characterized by Fourier transform infra-red (FTIR) spectroscopy, Raman spectroscopy, scanning electron microscope-energy dispersive X-ray spectroscopy (SEM-EDX), transmission electron microscopy (TEM), X-ray diffraction (XRD), particle size analysis (PSA), nitrogen adsorption/desorption and BET surface area analysis, X-ray photoelectron spectroscopy (XPS), inductively coupled plasma-optical emission spectrometry (ICP-OES), and in situ high temperature synchrotron XRD. The effects of ultrasonic irradiation time, and amplitude on the surface properties were investigated and the results confirmed that both parameters, especially amplitude, have significant effects on the physical properties of the prepared BG NPs. The XPS results showed that both, amplitude and time have a pronounced effect on the bridging and non-bridging oxygen atoms bonded to the Si centre in the BG samples, which play an important role in the bioactivity of the BG NPs. The in situ high temperature XRD patterns indicated a gradual phase transformation for the BG samples synthesized at different ultrasonic irradiation times and amplitudes. The TEM images showed that uniform nano-sized BG particles were obtained at 50% amplitude in only 10 minutes. A bimodal particle size distribution was observed with an increasing reaction time, up to 30 minutes, due to an increase in the formation of vortices at the interface where nucleation starts. All the prepared samples exhibited a glassy structure with the composition 70SiO2 : 25CaO : 5P2O5 and were highly bioactive. The proposed method would give a quick route for the synthesis of bioactive glasses and other ceramics with controlled physical properties.

Functionally Graded Multilayer Composites Based on Poly(D,L lactide)/Bioactive Fillers Fabricated by a 3D Direct Pellet Printing Multi-Extrusion Process

The aim of the present work was to investigate a 3D manufacturing process dealing with 3D Direct Pellet multi-Extrusion (DPPmE). Throughout this paper, various functionally graded materials (FGM) were obtained with tailored properties for bone regeneration. Therefore, an experimental investigation was performed to gain a better understanding of the structure-processing-properties relationships. A poly(D,l-lactic acid) (PDLLA) matrix and bioglass (BG) or hydroxyapatite (HA) bioactive fillers were chosen to obtain hybrid FGM in comparison to composite references. Different compositions and shape factors (from microspheres to fibers) of these bioactive fillers were used to control the PDLLA matrix degradation. Then, different strategies of DPPmE were used to tailor and tune the desired gradient of properties. Interestingly, good interfaces and adhesion properties were obtained. Subsequently, rheological, size-exclusion chromatography, and porosity measurements corroborated the present findings. Besides, tensile as well as thermomechanical properties showed the advantages of the DPPmE process to fabricate FGM composites with tailored architectures.

Collaborative Design of MgO/FeOx Nanosheets on Titanium: Combining Therapy with Regeneration.

The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeOx nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeOx double metal oxide demonstrates good peroxidase activity to catalyze H2 O2 , which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeOx film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.

Influence of pH in the synthesis of calcium phosphate based nanostructures with enhanced bioactivity and pro-angiogenic properties.

In synthetic fabrication, the process parameters decide the growth nucleation, phase translation, and the evolution of morphological facets of nanostructured materials. This work demonstrates the formation of different crystallographic phases of calcium phosphate by the influence of pH from acidic to alkaline conditions and also investigated their bone regeneration, protein adsorption, and pro-angiogenic properties. Present results illustrate that the alteration of pH is the crucial factor for the synthesis of calcium phosphate (CP) phases. The structural analysis reveals the monetite (CaHPO4 ) phase with a triclinic crystal system for pH 5, dual-phase of monetite combined with hydroxyapatite at the neutral pH 7, and pure phase of hydroxyapatite (Ca10 [PO4 ]6 OH2 ) with hexagonal structure at pH 10. Microscopic analysis portrays the cubic and rod-like morphologies by changing the pH values. FTIR and RAMAN spectroscopic analyses confirm the stretching, bending, and vibrational modes of dominant phosphate groups of different CP phases. Further, the biocompatibility of the prepared CP phases was examined by hemolysis assay, which showed less than 2% of lysis and enhanced cell viability. Moreover, the bioactivity study revealed rapid mineralization and a higher protein adsorption rate for the monetite CP phase (M-CP). Subsequently, the chick embryo angiogenesis assay elucidated 33% higher neovascularization for M-CP compared with the other two CP phases. The fabricated M-CP nanostructure constitutes a promising candidate for biomedical applications.

A self-assembled bilayer polypeptide-engineered hydrogel for spatiotemporal modulation of bactericidal and anti-inflammation process in osteomyelitis treatment

BackgroundDrug resistance of pathogens and immunosuppression are the main causes of clinical stagnation of osteomyelitis. The ideal treatment strategy for osteomyelitis is to achieve both efficient antibacterial and bone healing through spatiotemporal modulation of immune microenvironment.MethodsIn this study, a bilayer hydrogel based on genetically engineered polypeptide AC10A and AC10ARGD was prepared by self-assembly. Ag2S QDs@DSPE-mPEG2000-Ce6/Aptamer (AD-Ce6/Apt) was loaded in the top layer AC10A hydrogel (AA) for antibacterial, and bone marrow-derived mesenchymal stem cells (BMSCs) were loaded in the lower layer AC10ARGD hydrogel (MAR) for bone healing. The AD-Ce6/Apt can be released from the AA hydrogel to target S. aureus before bacterial biofilm formation and achieved significant bactericidal effect under irradiation with a 660 nm laser. Moreover, AD-Ce6/Apt can induce M1 type polarization of macrophages to activate the immune system and eliminate residual bacteria. Subsequently, BMSCs released from the MAR hydrogel can differentiate into osteoblasts and promote the formation of an anti-inflammatory microenvironment by regulating the M2 type polarization of macrophages. The bilayer AA-MAR hydrogel possessed good biocompatibility.ResultsThe in vitro and in vivo results showed that the AA-MAR hydrogel not only realized efficient photodynamic therapy of S. aureus infection, but also promoted the transformation of immune microenvironment to fulfill the different needs of each stage, which ultimately improved bone regeneration and mechanical properties post-surgery.ConclusionThis work presents an approach for spatiotemporal modulation of immune microenvironment in the treatment of osteomyelitis.Graphical

Biomimetic, mussel-inspired surface modification of 3D-printed biodegradable polylactic acid scaffolds with nano-hydroxyapatite for bone tissue engineering.

Polylactic acid (PLA) has been widely used as filaments for material extrusion additive manufacturing (AM) to develop patient-specific scaffolds in bone tissue engineering. Hydroxyapatite (HA), a major component of natural bone, has been extensively recognized as an osteoconductive biomolecule. Here, inspired by the mussel-adhesive phenomenon, in this study, polydopamine (PDA) coating was applied to the surface of 3D printed PLA scaffolds (PLA@PDA), acting as a versatile adhesive platform for immobilizing HA nanoparticles (nHA). Comprehensive analyses were performed to understand the physicochemical properties of the 3D-printed PLA scaffold functionalized with nHA and PDA for their potent clinical application as a bone regenerative substitute. Scanning electron microscopy (SEM) and element dispersive X-ray (EDX) confirmed a successful loading of nHA particles on the surface of PLA@PDA after 3 and 7 days of coating (PLA@PDA-HA3 and PLA@PDA-HA7), while the surface micromorphology and porosity remain unchanged after surface modification. The thermogravimetric analysis (TGA) showed that 7.7 % and 12.3% mass ratio of nHA were loaded on the PLA scaffold surface, respectively. The wettability test indicated that the hydrophilicity of nHA-coated scaffolds was greatly enhanced, while the mechanical properties remained uncompromised. The 3D laser scanning confocal microscope (3DLS) images revealed that the surface roughness was significantly increased, reaching Sa (arithmetic mean height) of 0.402 μm in PLA@PDA-HA7. Twenty-eight days of in-vitro degradation results showed that the introduction of nHA to the PLA surface enhances its degradation properties, as evidenced by the SEM images and weight loss test. Furthermore, a sustainable release of Ca2+ from PLA@PDA-HA3 and PLA@PDA-HA7 was recorded, during the degradation process. In contrast, the released hydroxyl group of nHA tends to neutralize the local acidic environments, which was more conducive to osteoblastic differentiation and extracellular mineralization. Taken together, this facile surface modification provides 3D printed PLA scaffolds with effective bone regenerative properties by depositing Ca2+ contents, improving surface hydrophilicity, and enhancing the in-vitro degradation rate.

A bioinformatics approach to study the role of calcium phosphate properties in bone regeneration

Calcium phosphates (CaPs) are extensively used as biomaterials for bone repair and regeneration and are considered an interesting synthetic alternative for natural bone grafts. However, the bone regenerative potential of many CaP bone graft substitutes requires further improvements. The bioactivity of CaPs is regulated by a variety of properties, including their chemical composition and (surface) structural properties. In this study, we performed a comprehensive characterization of six CaP ceramics that had been previously tested in several in vitro and in vivo studies, allowing us to in silico distinguish osteoinductive and non-osteoinductive CaP ceramics. The numerical parameters obtained from this characterization were further correlated with osteogenesis-associated gene expression and pathways of osteoblastic MG63 cells cultured on these six CaP ceramics. The results showed, among others, the influence of both chemical and structural parameters on cytoskeleton- and extracellular matrix-related gene expression and osteogenesis-associated pathways such as MAPK and BMP. The bioinformatics approach presented here allows exploring the transcriptional landscape induced by CaP ceramics and gaining fundamental knowledge about cell-biomaterial interactions.

Laddec® versus Bio-Oss®: The effect on the healing of critical-sized defect - Calvaria rabbit model.

The aim of this study was to evaluate the in vivo performance of two different deproteinized bovine bone (DBB) grafting materials: DBBB (Bio-Oss®) and DBBL (Laddec®), for the regeneration of critically sized (8 mm) defects in rabbit's calvaria. Three round-shaped defects were surgically created in the calvaria of 13 New Zealand White rabbits proximal to the coronal suture in the parietal bone. Two of the defects were filled with one of the grafting materials while a third was left empty to serve as a negative control. Bone regeneration properties were evaluated at 4- and 8-weeks after implantation by means of histological and histomorphometrical analyses. Statistical analyses were performed through a mixed model analysis with fixed factors of time and material. Histological evaluation of the control group evidenced a lack of bridging bone formation across the defect sites at both evaluation time points. For the experimental groups, new bone formation was observed around the defect periphery and to progress radially inwards to the center of the defect site, regardless of the grafting material. Histomorphometric analyses at 4 weeks demonstrated higher amount of bone formation through the defect for DBBB group. However, at 8 weeks, DBBL and DBBB demonstrated osteoconductivity and low resorption rates with evidence of statistically similar bone regeneration through the complete boney defect. Finally, DBBB presented lower soft tissue migration within the defect when compared to DBBL at both evaluation time points. DBBB and DBBL presented similar bone regeneration performance and slow resorption rates. Although both materials promoted bone regeneration through the complete defect, DBBB presented lower soft tissue migration within the defects at 4- and 8-weeks.

Triple-functional injectable liposome–hydrogel composite enhances bacteriostasis and osteo/angio-genesis for advanced maxillary sinus floor augmentation

Bone-grafting biological materials are commonly used to increase the height of the alveolar bone in the maxillary posterior region during maxillary sinus floor augmentation. However, there has been little research on the development of an injectable bone-grafting material with bacteriostatic, angiogenic, and osteogenic properties. In this work, we developed a triple-functional vancomycin/deferoxamine/dexamethasone (Van/DFO/Dex) liposome–hydrogel composite with desirable injectability. The release kinetics confirmed orderly sustained release of Van (a bacteriostat), DFO (a vascularised small molecule), and Dex (an osteogenic small molecule). In vitro findings demonstrated the favourable cytocompatibility and antibacterial ability of this composite against Staphylococcus aureus. Additionally, the angiogenic ability of human umbilical vein endothelial cells and osteogenic differentiation activity of MC3T3-E1 cells were enhanced. An in vivo bacteriostasis assay and rabbit maxillary sinus floor augmentation model corroborated the enhanced bacteriostasis and vascularised bone regeneration properties of this functionalised composite. Overall, the favourable injectability to be fit for the minimally invasive procedure, locally sustained release property, and prominent biological functions underscore the clinical potential of Van/DFO/Dex as an ideal bone-grafting material for irregular bone defect repairs, such as maxillary sinus floor augmentation.

Wollastonite and tricalcium phosphate composites for bone regeneration

In recent decades, researchers in bone tissue bioengineering have focused on developing and improving bioceramics efficient in presenting physical-chemical characteristics similar to bone tissue, aiming to mimic cellular events and mechanisms involved in osteogenesis. Among the materials used, wollastonite (W) has stood out in recent years, mainly due to its bioactivity. Besides, tricalcium phosphate (TCP) is also used primarily due to its osteoinductivity and osteoconductivity. Given their ionic compositions and the physical-chemical properties of W and TCP, scientists have associated these two materials during the synthesis of bioceramics that unite the characteristics of each material into a single biomaterial, called composite. This design enables a variety of association that allows improvements in the biological behavior of these materials. Therefore, W/TCP composites have shown excellent performance, in vitro and in vivo, as they start to exhibit fundamental properties for bone regeneration. These characteristics indicate the use of these new biomaterials in future clinical applications, especially in cases of extensive bone losses, which remain a significant challenge for scientists and biomedical professionals. Nevertheless, despite the advances achieved, many questions must be clarified, and essential to comprehend the mechanisms involved in osteogenesis after implantation. Thus, this study aimed to contextualize the use of W/TCP composites for bone regeneration, to support further studies necessary to identify the biological behavior of these bioceramics and ensure use in clinical practice.

Customized Design 3D Printed PLGA/Calcium Sulfate Scaffold Enhances Mechanical and Biological Properties for Bone Regeneration

Polylactic glycolic acid copolymer (PLGA) has been widely used in tissue engineering due to its good biocompatibility and degradation properties. However, the mismatched mechanical and unsatisfactory biological properties of PLGA limit further application in bone tissue engineering. Calcium sulfate (CaSO4) is one of the most promising bone repair materials due to its non-immunogenicity, well biocompatibility, and excellent bone conductivity. In this study, aiming at the shortcomings of activity-lack and low mechanical of PLGA in bone tissue engineering, customized-designed 3D porous PLGA/CaSO4 scaffolds were prepared by 3D printing. We first studied the physical properties of PLGA/CaSO4 scaffolds and the results showed that CaSO4 improved the mechanical properties of PLGA scaffolds. In vitro experiments showed that PLGA/CaSO4 scaffold exhibited good biocompatibility. Moreover, the addition of CaSO4 could significantly improve the migration and osteogenic differentiation of MC3T3-E1 cells in the PLGA/CaSO4 scaffolds, and the PLGA/CaSO4 scaffolds made with 20 wt.% CaSO4 exhibited the best osteogenesis properties. Therefore, calcium sulfate was added to PLGA could lead to customized 3D printed scaffolds for enhanced mechanical properties and biological properties. The customized 3D-printed PLGA/CaSO4 scaffold shows great potential for precisely repairing irregular load-bearing bone defects.

Integrity of the ECM Influences the Bone Regenerative Property of ECM/Dicalcium Phosphate Composite Scaffolds.

Due to the limitation of clinical autologous bone supply and other issues, the development of bone regeneration materials is still a hot topic. Natural tissue-derived bone repair materials have good biocompatibility and degradability, but their structure and properties are likely to be adversely affected during terminal sterilization. In this study, a composite scaffold consisting of the acellular extracellular matrix and dicalcium phosphate (ECM/DCP) was fabricated and terminally sterilized by γ-ray irradiation. In addition, the ECM/DCP scaffold was saturated with water and was also sterilized by γ-ray irradiation (RX-ECM/DCP). Results showed that the triple helix structure of collagen was better maintained in RX-ECM/DCP than in ECM/DCP. The thermal stability of RX-DCP/ECM was much better than that of ECP/ECM. The in vitro and in vivo performances of both types of scaffolds were also evaluated. The RX-ECM/DCP scaffold exhibited better in vitro bioactivity than that of the ECM/DCP scaffold as evidenced by more mineral formation in the simulated body fluid. In addition, RX-ECM/DCP also induced more effective bone regeneration than the ECM/DCP scaffold did in a rat calvarial defect model. Results sufficiently demonstrated that the addition of water to the scaffold could protect the structure of the ECM/DCP scaffold from being damaged by γ-ray irradiation during the terminal sterilization process. In summary, this study demonstrated a means to protect the ECM structure, which in turn led to the improvement of bone regenerative properties of the materials during γ-ray irradiation of ECM-based bone repair materials.

Implant degradation of low-alloyed Mg–Zn–Ca in osteoporotic, old and juvenile rats

Implant removal is unnecessary for biodegradable magnesium (Mg)-based implants and, therefore, the related risk for implant-induced fractures is limited. Aging, on the other hand, is associated with low bone-turnover and decreased bone mass and density, and thus increased fracture risk. Osteoporosis is accompanied by Mg deficiency, therefore, we hypothesized that Mg-based implants may support bone formation by Mg2+ ion release in an ovariectomy-induced osteoporotic rat model. Hence, we investigated osseointegration and implant degradation of a low-alloyed, degrading Mg–Zn–Ca implant (ZX00) in ovariectomy-induced osteoporotic (Osteo), old healthy (OH), and juvenile healthy (JH) groups of female Sprague Dawley rats via in vivo micro-computed tomography (µCT). For the Osteo rats, we demonstrate diminished trabecular bone already after 8 weeks upon ovariectomy and significantly enhanced implant volume loss, with correspondingly pronounced gas formation, compared to the OH and JH groups. Sclerotic rim development was observed in about half of the osteoporotic rats, suggesting a prevention from foreign-body and osteonecrosis development. Synchrotron radiation-based µCT confirmed lower bone volume fractions in the Osteo group compared to the OH and JH groups. Qualitative histological analysis additionally visualized the enhanced implant degradation in the Osteo group. To date, ZX00 provides an interesting implant material for young and older healthy patients, but it may not be of advantage in pharmacologically untreated osteoporotic conditions. Statement of significanceMagnesium-based implants are promising candidates for treatment of osteoporotic fractures because of their biodegradable, biomechanical, anti-bacterial and bone regenerative properties. Here we investigate magnesium‒zinc‒calcium implant materials in a rat model with ovariectomy-induced osteoporosis (Osteo group) and compare the related osseointegration and implant degradation with the results obtained for old healthy (OH) and juvenile healthy (JH) rats. The work applied an appropriate disease model for osteoporosis and focused in particular on long-term implant degradation for different bone conditions. Enhanced implant degradation and sclerotic rim formation was observed in osteoporotic rats, which illustrates that the setting of different bone models generates significantly modified clinical outcome. It further illustrated that these differences must be taken into account in future biodegradable implant development.

Biomimetic Antibacterial Pro-Osteogenic Cu-Sericin MOFs for Osteomyelitis Treatment.

Osteomyelitis is an inflammation of the bone caused by bacterial infection. It usually develops from broken bones, decayed teeth, or heavily punctured wounds. Multi-drug-resistant bacteria are the major hurdle in the treatment of osteomyelitis. The ever-rising antibiotic resistance even leads to amputations or fatalities as a consequence of chronic osteomyelitis. Hence, a single agent with antibacterial activity as well as bone regenerative properties can serve as a potential off-the-shelf product in the treatment of osteomyelitis. Herein, the antibacterial and pro-osteogenic characteristics of copper sericin (Cu-SER) metal–organic frameworks (MOFs) are reported. Sericin, a silk protein with antibacterial activity and an osteoinduction property, acts as an organic template for the deposition of Cu-SER MOFs, similar to collagen during biomineralization in bone. The MOFs exhibit cytocompatibility and osteogenic activity in a dose-dependent manner, as revealed by cell proliferation (alamarBlue) and mineralization (Alizarin Red S and Energy Dispersive X-ray analysis). The bactericidal activity of Cu-SER MOFs was investigated by scanning electron microscopy and a growth kinetic analysis. Together, the report illuminates the unique phenomenon of Cu-SER MOFs that kill bacteria upon contact while being well-tolerated by primary human cells. Hence, Cu-SER MOFs hold the potential to minimize antibiotic dependence.

Combining Mg-Zn-Ca Bulk Metallic Glass with a Mesoporous Silica Nanocomposite for Bone Tissue Engineering.

Mg–Zn–Ca bulk metallic glass (BMG) is a promising orthopedic fixation implant because of its biodegradable and biocompatible properties. Structural supporting bone implants with osteoinduction properties for effective bone regeneration have been highly desired in recent years. Osteogenic growth peptide (OGP) can increase the proliferation and differentiation of mesenchymal stem cells and enhance the mineralization of osteoblast cells. However, the short half-life and non-specificity to target areas limit applications of OGP. Mesoporous silica nanoparticles (MSNs) as nanocarriers possess excellent properties, such as easy surface modification, superior targeting efficiency, and high loading capacity of drugs or proteins. Accordingly, we propose a system of combining the OGP-containing MSNs with Mg–Zn–Ca BMG materials to promote bone regeneration. In this work, we conjugated cysteine-containing OGP (cgOGP, 16 a.a.) to interior walls of channels in MSNs and maintained the dispersity of MSNs via PEGylation. An in vitro study showed that metal ions released from Mg–Zn–Ca BMG promoted cell proliferation and migration and elevated alkaline phosphatase (ALP) activity and mineralization. On treating cells with both BMG ion-containing Minimum Essential Medium Eagle-alpha modification (α-MEM) and OGP-conjugated MSNs, enhanced focal adhesion turnover and promoted differentiation were observed. Hematological analyses showed the biocompatible nature of this BMG/nanocomposite system. In addition, in vivo micro-computed tomographic and histological observations revealed that our system stimulated osteogenesis and new bone formation around the implant site.

Electrospun Membrane Surface Modification by Sonocoating with HA and ZnO:Ag Nanoparticles-Characterization and Evaluation of Osteoblasts and Bacterial Cell Behavior In Vitro.

Guided tissue regeneration and guided bone regeneration membranes are some of the most common products used for bone regeneration in periodontal dentistry. The main disadvantage of commercially available membranes is their lack of bone cell stimulation and easy bacterial colonization. The aim of this work was to design and fabricate a new membrane construct composed of electrospun poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) fibers sonocoated with layers of nanoparticles with specific properties, i.e., hydroxyapatite and bimetallic nanocomposite of zinc oxide–silver. Thus, within this study, four different variants of biomaterials were evaluated, namely: poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) biomaterial, poly(D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite biomaterial, poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano zinc oxide–silver biomaterial, and poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite/nano zinc oxide–silver biomaterial. First, it was demonstrated that the wettability of biomaterials—a prerequisite property important for ensuring desired biological response—was highly increased after the sonocoating process. Moreover, it was indicated that biomaterials composed of poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) with or without a nano hydroxyapatite layer allowed proper osteoblast growth and proliferation, but did not have antibacterial properties. Addition of a nano zinc oxide–silver layer to the biomaterial inhibited growth of bacterial cells around the membrane, but at the same time induced very high cytotoxicity towards osteoblasts. Most importantly, enrichment of this biomaterial with a supplementary underlayer of nano hydroxyapatite allowed for the preservation of antibacterial properties and also a decrease in the cytotoxicity towards bone cells, associated with the presence of a nano zinc oxide–silver layer. Thus, the final structure of the composite poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite/nano zinc oxide–silver seems to be a promising construct for tissue engineering products, especially guided tissue regeneration/guided bone regeneration membranes. Nevertheless, additional research is needed in order to improve the developed construct, which will simultaneously protect the biomaterial from bacterial colonization and enhance the bone regeneration properties.