The Guided Bone Regeneration (GBR) treatment concept advocates that regeneration of osseous defects is predictably attainable via the application of occlusive membranes, which mechanically exclude non-osteogenic cell populations from the surrounding soft tissues, thereby allowing osteogenic cell populations originating from the parent bone to inhabit the osseous wound. The present review discusses the evolution of the GBR biological rationale and therapeutic concept over the last two decades. Further, an overview of the GBR research history is provided with specific focus on the evidence available on its effectiveness and predictability in promoting the regeneration of critical size cranio-maxillo-facial defects, the neo-osteogenesis potential and the reconstruction of atrophic alveolar ridges before, or in conjunction with, the placement of dental implants. The authors conclude that future research should focus on (a) the investigation of the molecular mechanisms underlying the wound healing process following GBR application; (b) the identification of site and patient related factors which impact on the effectiveness and predictability of GBR therapy and (c) the evaluation of the pathophysiology of the GBR healing process in the presence of systemic conditions potentially affecting the skeletal system.To cite this article:Retzepi M, Donos N. Guided Bone Regeneration: biological principle and therapeutic applications.Clin. Oral Impl. Res. 21, 2010; 567-576.doi: 10.1111/j.1600-0501.2010.01922.x.

Guided Bone Regeneration: biological principle and therapeutic applications

Advances in nanoparticle (NP) production and demand for control over nanoscale systems have had significant impact on tissue engineering and regenerative medicine (TERM). NPs with low toxicity, contrasting agent properties, tailorable characteristics, targeted/stimuli-response delivery potential, and precise control over behavior (via external stimuli such as magnetic fields) have made it possible their use for improving engineered tissues and overcoming obstacles in TERM. Functional tissue and organ replacements require a high degree of spatial and temporal control over the biological events and also their real-time monitoring. Presentation and local delivery of bioactive (growth factors, chemokines, inhibitors, cytokines, genes etc.) and contrast agents in a controlled manner are important implements to exert control over and monitor the engineered tissues. This need resulted in utilization of NP based systems in tissue engineering scaffolds for delivery of multiple growth factors, for providing contrast for imaging and also for controlling properties of the scaffolds. Depending on the application, materials, as polymers, metals, ceramics and their different composites can be utilized for production of NPs. In this review, we will cover the use of NP systems in TERM and also provide an outlook for future potential use of such systems.

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Use of Nanoparticles in Tissue Engineering and Regenerative Medicine.

In recent years, porous bioactive glass micro/nanospheres (PBGSs) have emerged as attractive biomaterials in various biomedical applications where such engineered particles provide suitable functions, from tissue engineering to drug delivery. The design and synthesis of PBGSs with controllable particle size and pore structure are critical for such applications. PBGSs have been successfully synthesized using melt-quenching and sol-gel based methods. The morphology of PBGSs is controllable by tuning the processing parameters and precursor characteristics during the synthesis. In this comprehensive review on PBGSs, we first overview the synthesis approaches for PBGSs, including both melt-quenching and sol-gel based strategies. Sol-gel processing is the primary technology used to produce PBGSs, allowing for control over the chemical compositions and pore structure of particles. Particularly, the influence of pore-forming templates on the morphology of PBGSs is highlighted. Recent progress in the sol-gel synthesis of PBGSs with sophisticated pore structures (e.g., hollow mesoporous, dendritic fibrous mesoporous) is also covered. The challenges regarding the control of particle morphology, including the influence of metal ion precursors and pore expansion, are discussed in detail. We also highlight the recent achievements of PBGSs in a number of biomedical applications, including bone tissue regeneration, wound healing, therapeutic agent delivery, bioimaging, and cancer therapy. Finally, we conclude with our perspectives on the directions of future research based on identified challenges and potential new developments and applications of PBGSs.

Porous bioactive glass micro- and nanospheres with controlled morphology: developments, properties and emerging biomedical applications

https://doi.org/10.1016/j.bioactmat.2022.05.018

Cellulose-based composite scaffolds for bone tissue engineering and localized drug delivery

An injectable click-crosslinked hyaluronic acid hydrogel modified with a BMP-2 mimetic peptide as a bone tissue engineering scaffold.

Every year, many dental restoration methods are carried out in the world and most of them do not succeed. High cost of these restorations and rejection possibility of the implants are main drawback...

In vitro performance of a nanobiocomposite scaffold containing boron-modified bioactive glass nanoparticles for dentin regeneration.

Evaluation of human dental pulp stem cells behavior on a novel nanobiocomposite scaffold prepared for regenerative endodontics

Barrier membranes are used in periodontal tissue engineering for successful neo-bone tissue formation and prevention of bacterial colonization. We aimed to prepare and characterize novel 7% boron-modified bioactive glass (7B-BG) containing bilayered membrane for this end. We hypothesized that presence of 7B-BG could promote structural and biological properties of guided bone regeneration (GBR) membrane. Cellulose acetate (CA) layer was prepared by solvent casting, and functionally graded layer of CA/gelatin/BG nanoparticles was prepared by electrospinning. 0B-BG, and 7B-BG were synthesized by quick alkali-mediated sol-gel method and were characterized by scanning electron microscopy (SEM) and Fourier-transform Raman spectroscopy. Membranes were cross-linked with glutaraldehyde to preserve their stability. SEM analysis showed the asymmetric nature of membranes consisting of a smooth membrane layer and a rough surface composed of 0B-BG and 7B-BG containing nanofibres. 7B-BG addition increased surface wettability (from 110.5° ± 0.8 to 73.46° ± 7.6) and biodegradability of the membranes. Additionally, a significant increase in Ca-P layer formation was observed in 7B-BG containing group after 1-week incubation in stimulated body fluid. 7B-BG incorporation resulted in a decrease in tensile strength and Young's modulus values. Human dental pulp stem cells showed better attachment, spreading, and proliferation on 7B-BG containing bilayered membranes. Osteogenic differentiation analysis revealed higher alkaline phosphatase (ALP) enzyme activity of cells (~1.5-fold), higher intracellular calcium deposition (approximately twofold), and higher calcium deposition revealed by Alizarin red staining on 7B-BG containing bilayered membranes. Overall, results suggested that functionally graded bilayered membranes hold potential for GBR applications in regenerative dentistry.

Development of a novel functionally graded membrane containing boron-modified bioactive glass nanoparticles for guided bone regeneration.

In this study, we aimed to prepare and characterize porous scaffolds composed of pure and boron oxide (B2O3)-doped bioactive glass (BG) that were infiltrated by cellulose acetate-gelatin (CA-GE) polymer solution for bone tissue engineering applications. Composite scaffolds were cross-linked with glutaraldehyde after polymer coating to protect the structural integrity of the polymeric-coated scaffolds. The impact of B2O3 incorporation into BG-polymer porous scaffolds on the cross-sectional morphology, porosity, mechanical properties, degradation and bioactivity of the scaffolds was investigated. Human dental pulp stem cells (hDPSCs) were enzymatically isolated and used for cell culture studies. According to scanning electron microscope analysis, the porous structure of the scaffolds was preserved after polymer coating. After polymer infiltration, the porosity of the scaffolds decreased from 64.2% to 59.35% for pure BG scaffolds and from 67.3% to 58.9% for B2O3-doped scaffolds. Meanwhile, their compressive strengths increased from 0.13 to 0.57 MPa and from 0.20 to 0.82 MPa, respectively. After polymer infiltration, 7% B2O3-incorporated BG scaffolds had higher weight loss and Ca-P layer deposition than pure BG scaffolds, after 14 d of incubation in simulated body fluid at 37 °C. Higher attachment and proliferation of hDPSCs were observed on 7% B2O3-BG-CA/GE scaffolds. In addition, the alkaline phosphatase activity of the cells was about 1.25-fold higher in this group than that observed on BG-CA/GE scaffolds after 14 d of incubation in osteogenic medium, while their intracellular calcium amounts were 1.7-fold higher than observed on BG-CA/GE after 7 d of incubation in osteogenic medium. Our results suggested that porous cellulose acetate-gelatin-coated boron-BG scaffolds hold promise for bone tissue engineering applications.

Cellulose acetate-gelatin-coated boron-bioactive glass biocomposite scaffolds for bone tissue engineering.

Strontium (Sr2+) and fluoride (F−) ions are known to play an important role in bone and tooth metabolism. In this work, we prepare biphasic calcium phosphate (BCP) bioceramics co-doped with different fractions of Sr2+ and F− ions to investigate the impact of dopant on the crystal structure and biological properties of BCP bioceramics. The materials were successfully synthesized using a wet precipitation method, followed by sintering at 1100 °C for 1 h. The sintered materials were characterized using x-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and field emission scanning electron microscopy (FESEM). XRD analysis revealed that the BCP bioceramics were composed of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), along with calcium oxide (CaO) as impurity. Furthermore, the percentage of β-TCP tended to increase with an increase in the Sr2+ ion concentration. The lattice parameters of HA phase expanded along with incorporation of Sr2+ and F− ions. The morphology of the yielding materials demonstrated that the incorporation of Sr2+ and F− ions caused a decrease in the grain size. The Vickers hardness (HV) test showed that hardness values increased with increasing Sr2+ concentrations. In vitro cell culture tests were performed with human osteogenic sarcoma (Saos-2) cell line. Saos-2 cells attached and proliferated faster on Sr/F-BCP materials compared to pure BCP, showing that Sr/F-BCP materials were cytocompatible.

https://iopscience.iop.org/article/10.1088/2057-1976/aa768c/pdf

Reza Moonesi Rad

Papers

In vitro performance of a nanobiocomposite scaffold containing boron-modified bioactive glass nanoparticles for dentin regeneration.

Evaluation of human dental pulp stem cells behavior on a novel nanobiocomposite scaffold prepared for regenerative endodontics

Development of a novel functionally graded membrane containing boron-modified bioactive glass nanoparticles for guided bone regeneration.

Cellulose acetate-gelatin-coated boron-bioactive glass biocomposite scaffolds for bone tissue engineering.

Strontium and fluorine co-doped biphasic calcium phosphate: characterization and in vitro cytocompatibility analysis