Guided Bone Regeneration Applications Research Articles

Resorbable engineered barrier membranes for oral surgery applications.

Population aging, reduced economic capacity, and neglecting the treatments for oral pathologies, are the main causal factors for about 3 billion individuals who are suffering from partial/total edentulism or alveolar bone resorption: thus, the demand for dental implants is increasingly growing. To achieve a good prognosis for implant-supported restorations, adequate peri-implant bone volume is mandatory. The Guided Bone Regeneration (GBR) technique is one of the most applied methods for alveolar bone reconstruction and treatment of peri-implant bone deficiencies. This technique involves the use of different types of membranes in association with some bone substitutes (autologous, homologous, or heterologous). However, time for bone regeneration is often too long and the bone quality is not simply predictable. This study aims at engineering and evaluating the efficacy of modified barrier membranes, enhancing their bioactivity for improved alveolar bone tissue regeneration. We investigated membranes functionalized with chitosan (CS) and chitosan combined with the peptide GBMP1α (CS + GBMP1α), to improve bone growth. OsseoGuard® membranes, derived from bovine Achilles tendon type I collagen crosslinked with formaldehyde, were modified using CS and CS + GBMP1α. The functionalization, carried out with 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide and sulfo-N-Hydroxysuccinimide (EDC/sulfo-NHS), was assessed through FT-IR and XPS analyses. Biological assays were performed by directly seeding human osteoblasts onto the materials to assess cell proliferation, mineralization, gene expression of Secreted Phosphoprotein 1 (SPP1) and Runt-Related Transcription Factor 2 (Runx2), and antibacterial properties. Both CS and CS + GBMP1α functionalizations significantly enhanced human osteoblast proliferation, mineralization, gene expression, and antibacterial activity compared to commercial membranes. The CS + GBMP1α functionalization exhibited superior outcomes in all biological assays. Mechanical tests showed no significant alterations of membrane biomechanical properties post-functionalization. The engineered membranes, especially those functionalized with CS + GBMP1α, are suitable for GBR applications thanks to their ability to enhance osteoblast activity and promote bone tissue regeneration. These findings suggest a potential advancement in the treatment of oral cavity problems requiring bone regeneration.

Self-composite silk fibroin membranes for guided bone regeneration: 1 material 3 architectures with intrinsic integrity

Silk fibroin (SF) takes attention in tissue engineering due to unique features, e.g., excellent biocompatibility/biodegradability with superior mechanical/thermal properties despite its lightweight. Guided bone regeneration (GBR) seeks bilayered GBR membranes to govern bone regeneration, although constituent parts of such membranes may undergo delamination once different biomaterials are combined. Herein, 3-component bilayered SF membranes were prepared for the first time utilizing the same polymer in different forms by eliminating the delamination risk of layers for GBR applications. One side consisted of a non-porous SF film serving as a barrier against penetration of non-osteogenic tissue whereas the other side was porous/fibrous composed of SF sponge and SF fibers for bone regeneration. Proper integration between these layers was confirmed via scanning electron microscopy (SEM). Composites reinforced with high fiber percent (30%) had remarkably enhanced compressive strength and elastic moduli, which were further improved by increasing polymer concentration from 4% to 8%. Non-porous morphology of the barrier side was preserved during 28 days of degradation while pore sizes enlarged on the other surface, which would be beneficial for cell migration into the regenerative side. Saos-2 cells seeded on composites with high fiber percent proliferated more within 14 days; however, alkaline phosphatase (ALP) activity on low-fiber-percent counterparts was elevated more. Osteogenic marker gene expressions were significantly higher than control on day 14. All self-composites were eminent candidates to promote bone regeneration with tailor-made capacity for further improvements. Taken together, 1-material 3-architecture SF fabricated by a green and practical technique holds promise for GBR applications.

Development, Characterisation and Biocompatibility Analysis of a Collagen-Gelatin-Hydroxyapatite Scaffold for Guided Bone Regeneration

Guided Bone Regeneration (GBR) is the choice of treatment for improving the horizontal and vertical bone volume through bone grafting. GBR membranes work on the principle of preventing epithelial migration into the defect space while maintaining the space for cell migration and differentiation at the defect site. Hydroxyapatite has been commonly used as a bone graft for infrabony defects. The study was conducted at the Department of Biomaterials at Saveetha Dental College. GBR membrane was prepared and its material characterization was done using Scanning Electron Microscope (SEM), Energy Dispersive X-ray (EDX) analysis, Fourier Transform Infrared Radiation (FTIR), and Confocal Analysis. The developed GBR membrane revealed SEM properties conducive to cell attachment. EDX and FTIR analysis showed the successful development of the collagen-gelatin-hydroxyapatite membrane. Cell culture and confocal analysis revealed excellent biocompatibility with a homogenous layer of viable cells. The developed composite GBR membrane is a biogenic membrane with relevant biomineralization potential that should be applied for GBR applications.

Porous Nano-Fiber Structure of Modified Electrospun Chitosan GBR Membranes Improve Osteoblast Calcium Phosphate Deposition in Osteoblast-Fibroblast Co-Cultures.

Desirable characteristics of electrospun chitosan membranes (ESCM) for guided bone regeneration are their nanofiber structure that mimics the extracellular fiber matrix and porosity for the exchange of signals between bone and soft tissue compartments. However, ESCM are susceptible to swelling and loss of nanofiber and porous structure in physiological environments. A novel post-electrospinning method using di-tert-butyl dicarbonate (tBOC) prevents swelling and loss of nanofibrous structure better than sodium carbonate treatments. This study aimed to evaluate the hypothesis that retention of nanofiber morphology and high porosity of tBOC-modified ESCM (tBOC-ESCM) would support more bone mineralization in osteoblast-fibroblast co-cultures compared to Na2CO3 treated membranes (Na2CO3-ESCM) and solution-cast chitosan solid films (CM-film). The results showed that only the tBOC-ESCM retained the nanofibrous structure and had approximately 14 times more pore volume than Na2CO3-ESCM and thousands of times more pore volume than CM-films, respectively. In co-cultures, the tBOC-ESCM resulted in a significantly greater calcium-phosphate deposition by osteoblasts than either the Na2CO3-ESCM or CM-film (p < 0.05). This work supports the study hypothesis that tBOC-ESCM with nanofiber structure and high porosity promotes the exchange of signals between osteoblasts and fibroblasts, leading to improved mineralization in vitro and thus potentially improved bone healing and regeneration in guided bone regeneration applications.

Soybean Oil-Based 3D Printed Mesh Designed for Guided Bone Regeneration (GBR) in Oral Surgery.

This study aims to obtain a cyto-compatible 3D printable bio-resin for the manufacturing of meshes designed from acquired real patients' bone defect to be used in future for guided bone regeneration (GBR), achieving the goal of personalized medicine, decreasing surgical, recovery time, and patient discomfort. To this purpose, a biobased, biocompatible, and photo-curable resin made of acrylated epoxidized soybean oil (AESO) diluted with soybean oil (SO) is developed and 3D printed using a commercial digital light processing (DLP) 3D printer. 3D printed samples show good thermal properties, allowing for thermally-based sterilization process and mechanical properties typical of crosslinked natural oils (i.e., E = 12MPa, UTS = 1.5MPa), suitable for the GBR application in the oral surgery. The AESO-SO bio-resin proves to be cytocompatible, allowing for fibroblast cells proliferation (viability at 72h > 97%), without inducing severe inflammatory response when co-cultured with macrophages, as demonstrated by cytokine antibody arrays, that is anyway resolved in the first 24 h. Moreover, accelerated degradation tests prove that the bio-resin is biodegradable in hydrolytic environments.

A novel bi-layered asymmetric membrane incorporating demineralized dentin matrix accelerates tissue healing and bone regeneration in a rat skull defect model.

Objectives: The technique of guided bone regeneration (GBR) has been widely used in the field of reconstructive dentistry to address hard tissue deficiency. The objective of this research was to manufacture a novel bi-layered asymmetric membrane that incorporates demineralized dentin matrix (DDM), a bioactive bone replacement derived from dentin, in order to achieve both soft tissue isolation and hard tissue regeneration simultaneously. Methods: DDM particles were harvested from healthy, caries-free permanent teeth. The electrospinning technique was utilized to synthesize bi-layered DDM-loaded PLGA/PLA (DPP) membranes. We analyzed the DPP bilayer membranes' surface topography, physicochemical properties and degradation ability. Rat skull critical size defects (CSDs) were constructed to investigate in vivo bone regeneration. Results: The synthesized DPP bilayer membranes possessed suitable surface characteristics, acceptable mechanical properties, good hydrophilicity, favorable apatite forming ability and suitable degradability. Micro-computed tomography (CT) showed significantly more new bone formation in the rat skull defects implanted with the DPP bilayer membranes. Histological evaluation further revealed that the bone was more mature with denser bone trabeculae. In addition, the DPP bilayer membrane significantly promoted the expression of the OCN matrix protein in vivo. Conclusions: The DPP bilayer membranes exhibited remarkable biological safety and osteogenic activity in vivo and showed potential as a prospective candidate for GBR applications in the future.

The potential of nano graphene oxide and chlorhexidine composite membranes for use as a surface layer in functionally graded membranes for periodontal lesions

Membranes have been used for treating periodontal defects and play a crucial role in guided bone regeneration applications. Nano graphene oxide have been exploited in tissue engineering due to its biomechanical properties. Its composite formulations with hydroxyapatite and chitosan with controlled degradation could aid in becoming part of a surface layer in a functionally graded membrane. The aim of the study was to synthesize chitosan and composite formulations of nano graphene oxide, hydroxyapatite and chlorhexidine digluconate using solvent casting technique and to characterize the physiochemical, mechanical, water vapor transmission rate (barrier), degradation and antimicrobial potential of the membranes. Altogether four different membranes were prepared (CH, CCG, 3511 and 3322). Results revealed the chemical interactions of hydroxyapatite, chitosan and nanographene oxide due to inter and intra molecular hydrogen bonding. The tensile strength of 3322 (33.72 ± 6.3 MPa) and 3511 (32.06 ± 5.4 MPa) was higher than CH (27.46 ± 9.6 MPa). CCG showed the lowest water vapor transmission rate (0.23 ± 0.01 g/h.m2) but the highest weight loss at day 14 (76.6 %). 3511 showed a higher drug release after 72 h (55.6 %) Significant biofilm growth inhibition was observed for all membranes. 3511 showed complete inhibition against A. actinomycetemcomitans. Detailed characterization of the synthesized membranes revealed that 3511 composite membrane proved to be a promising candidate for use as a surface layer of membranes for guided bone regeneration of periodontal lesions.Graphical

Poly(lactic acid/caprolactone) bilayer membrane achieves bone regeneration through a prolonged barrier function.

Guided bone regeneration (GBR) is a treatment strategy used to recover bone volume. Barrier membranes are a key component of GBR protocols, and their properties can impact treatment outcomes. This study investigated the efficacy of an experimental, slow-degrading, bilayer barrier membrane for application in GBR using in vivo animal models. A synthetic copolymer of poly(lactic acid/caprolactone) (PLCL) was used to prepare a slow-degrading bilayer membrane. The biodegradability of PLCL was evaluated by subcutaneous implantation in a rat model. The barrier function of the PLCL membrane was investigated in a rat calvaria defect model and compared with commercially available membranes composed of type I collagen (Col) and poly(lactic-co-glycolic acid) (PLGA). An alveolar bone defect model in beagle dogs was used to simulate GBR protocols to evaluate the bone regeneration ability of the experimental PLCL membrane. The PLCL membrane showed slow biodegradation, resulting in an efficient and prolonged barrier function compared with commercial materials. In turn, this barrier function enabled the space-making ability of PLCL membrane and facilitated bone regeneration. In the alveolar bone defect model, significantly greater regeneration was achieved by treatment with PLCL membrane compared with Col and PLGA membranes. Additionally, a continuous alveolar ridge contour was observed in PLCL-treated bone defects. In conclusion, the PLCL bilayer membrane is a promising biomaterial for use in GBR given its slow degradation and prolonged barrier function.

Dual Mg-Reinforced PCL Membrane with a Janus Structure for Vascularized Bone Regeneration and Bacterial Elimination.

Commercially available guided bone regeneration (GBR) membranes often exhibit limited mechanical properties or bioactivity, leading to poor performance in repairing bone defects. To surmount this limitation, we developed a Janus structural composite membrane (Mg-MgO/PCL) reinforced by dual Mg (Mg sheets and MgO NPs) by using a combined processing technique involving casting and electrospinning. Results showed that the addition of Mg sheets and MgO NPs enhanced the mechanical properties of the composite membrane for osteogenic space maintenance, specifically tensile strength (from 10.2 ± 1.2 to 50.3 ± 4.5 MPa) and compression force (from 0 to 0.94 ± 0.09 N mm-1), through Mg sheet reinforcement and improved crystallization. The dense cast side of the Janus structure membrane displayed better fibroblast barrier capacity than a single fiber structure; meanwhile, the PCL matrix protected the Mg sheet from severe corrosion due to predeformation. The porous microfibers side supported preosteoblast cell adhesion, enhanced osteogenesis, and angiogenesis in vitro, through the biomimetic extracellular matrix and sustainable Mg2+ release. Furthermore, the Mg-MgO/PCL membrane incorporating 2 wt % MgO NPs exhibited remarkable antimicrobial properties, inducing over 88.75% apoptosis in Staphylococcus aureus. An in vivo experiment using the rat skull defect model (Φ = 5 mm) confirmed that the Mg-MgO/PCL membrane significantly improved new bone formation postsurgery. Collectively, our investigation provides valuable insights into the design of multifunctional membranes for clinical oral GBR application.

Synthesis of composite corn starch/hydroxyapatite nanoparticle biomembranes and their effect on mineralization by osteoblasts

AbstractBone defects and injuries are challenging issues in regenerative medicine. Guided bone regeneration (GBR) techniques use biomaterials as scaffolds to support the healing of damaged bone tissue. In this context, there is growing interest in developing new biomaterials with bioabsorbable and bioactive properties to increase GBR effectiveness. In this study, composite corn starch/hydroxyapatite nanoparticle (HAp) biomembranes were synthesized to achieve bioresorbable and bioactive properties compatible with applications in GBR. Starch is a renewable source and presents suitable rheological properties for membrane preparation; in turn, HAp is well known for its osteogenic properties. The biomembranes were prepared by solvent casting (5 wt% aqueous corn starch suspension containing different amounts of HAp (i.e., 0, 2, 5, and 10% of the corn starch weight), to give the membranes HAp_0%, HAp_2%, HAp_5%, and HAp_10%, respectively). The physicochemical and biological properties of the biomembranes were assessed. The concentrations of up to 10% of HAp were homogeneously dispersed in the composite biomembranes. HAp addition increased the biodegradability and the ability of the biomembranes to release Ca2+. The biomembranes containing HAp were more mechanically resistant and less flexible and were not toxic to osteoblasts. Moreover, compared to pure corn starch biomembranes, osteoblasts adhered better to the composite biomembranes. The higher the HAp content, the greater the mineralization promoted by osteoblasts on the composite biomembranes. HAp addition also resulted in composite biomembranes with better fracture healing efficiency in vitro. Therefore, composite corn starch/HAp biomembranes have excellent characteristics, including biodegradability, bioactivity, mechanical strength, and biocompatibility, for the development of new materials aimed at GBR.

Biocompatibility and histological responses of eggshell membrane for dental implant-guided bone regeneration.

Guided bone regeneration (GBR) utilizing eggshell membrane (ESM) as a potential biomaterial for dental implant therapy augmentation was explored in this study. ESM, an environmentally friendly waste product, possesses collagen-rich characteristics. The biocompatibility and histological responses of ESM were investigated in a rat model. Twelve young adult Wistar rats were used in this study. ESM samples were implanted in subcutaneous and intramuscular pockets, and samples were collected at 48 hours, 4 weeks, and 8 weeks post-implantation. Histological analysis revealed the changes in ESM over time. Results showed that ESM maintained its structural integrity, induced a moderate cellular response, and exhibited slow degradation, indicating potential biocompatibility. However, the lack of organized collagen arrangement in ESM led to the formation of irregular and polymorphic spaces, allowing cell migration. Encapsulation of ESM by newly proliferating collagen fibers and multinucleated giant cells was observed at later time points, indicating a foreign body reaction. Crosslinking might improve its performance as a separation membrane, as it has the potential to resist enzymatic degradation and enhance biomechanical properties. In conclusion, ESM demonstrated biocompatibility, slow degradation, and lack of foreign body reaction. While not suitable as a complete separation membrane due to irregular collagen arrangement, further research involving crosslinking could enhance its properties, making it a viable option for guided bone regeneration applications in dental implant therapy. This study highlights the potential of repurposing waste materials for medical purposes and underscores the importance of controlled collagen structure in biomaterial development.

ZnP‐Coated Zn1Cu0.1Ti Membrane with High Strength‐Ductility, Antibacterial Ability, Cytocompatibility, and Osteogenesis for Biodegradable Guided Bone Regeneration Applications

AbstractZinc (Zn) and its alloys have recently gained research interest due to their good biosafety, biological function, biodegradability, and formability. Zinc‐phosphate (ZnP) coating has been shown to improve the corrosion resistance and biocompatibility of Zn alloys. Here, a biodegradable ZnP‐coating on Zn1Cu0.1Ti (ZCT) membrane with high strength‐ductility and mechanical stability, suitable degradation rate, effective antibacterial ability, excellent in vitro and in vivo cytocompatibility, and osteogenesis is reported. The ZnP‐coated ZCT exhibits high strength‐ductility with a yield strength of 264 MPa, ultimate tensile strength of 312 MPa, elongation of 36.0%, and high mechanical stability before and after 30 d immersion in Hanks’ and AS solutions, all of which are higher than those of ZCT. The ZnP coating shows good deformation resistance, healing effect, and bond strength with the substrate, meeting the clinical contour shaping requirements. The ZnP‐coated ZCT membrane sample shows higher cell viability toward MC3T3‐E1 and MG‐63 cells, osteogenic and mitochondrial quality‐control properties in vitro than those of the ZCT sample. Using a rat calvarial defect model, the ZnP‐coated ZCT membrane shows complete biosafety and considerable osteogenesis performance. Overall, the ZnP‐coated ZCT membrane is recommended as a promising biodegradable implant material for oral guided bone regeneration application.

Plant-Derived Polyphenol and LL-37 Peptide-Modified Nanofibrous Scaffolds for Promotion of Antibacterial Activity, Anti-Inflammation, and Type-H Vascularized Bone Regeneration

The regeneration of oral tissues is a challenging clinical problem because of the complex microbial and biological stress environments. Electrospun fibrous scaffolds have attracted significant interest as effective barrier membranes for guided bone regeneration (GBR); however, no mature strategy yet exists for the surface modification of fibers to provide versatility to satisfy clinical requirements. This study demonstrated a practical biosafety strategy: the combined use of plant polyphenols and LL-37 peptides to modify the fiber surface to endow the fibrous scaffold with antimicrobial activity, immunoregulation, and vascularized bone regeneration. We confirmed that the LL-37 peptides interacted with tannic acid (TA) through noncovalent bonds through experiments and molecular docking simulation analysis. In vitro experiments showed that the TA coating imparted strong antibacterial properties to the fibrous scaffold, but it also caused cytotoxicity. The grafting of LL-37 peptide promoted the spreading, migration, and osteogenic differentiation of mesenchymal stem cells and was also conducive to the M2 polarization of RAW264.7 cells. In vivo experiments further verified that the LL-37 peptide-grafted fibrous scaffold significantly enhanced angiogenesis, anti-inflammatory effects, and type-H vascularized bone regeneration. Overall, the fibrous scaffold modified by the LL-37 peptide through TA grafting has significant potential for GBR applications.

Poly (l-lactic acid)-based modified nanofibrous membrane with dual drug release capability for GBR application

Electrospun multilayer nanofibers guided bone regeneration (GBR) with a new design were developed in this study. The synthesized multilayer GBR was composed of two distinct layers. Poly l-lactic acid (PLA) incorporated with simvastatin (SIM) was designed as PLA/SIM layer to contact with a bone defect. In addition, the hydrophilic gelatin (GT) containing thymol (THY) was fabricated as GT/THY layer to contact connective tissue, potentially for bacterial gathering. Due to the different chemical nature and weak cohesion of the hydrophilic and hydrophobic layers, hybrid fibers made of PLA/SIM and GT/THY were electrospun as cohesion promoters between these layers. The microstructure and characteristics of the synthesized multilayer substrate, named GT/PLA, were evaluated, and different fibrous monolayers were fabricated to determine the optimal concentrations of drugs.Scanning electron microscopy (SEM) images showed continuous, smooth, randomly aligned, and bead-free fibers. In addition, there were no drug particles on the fiber surfaces which displayed the good placement of those inside the fibers. The mats exhibited satisfactory tensile strength (4.60 ± 0.14 MPa) and favorable physicochemical properties, including proper porosity percentage (<50 %) and appropriate pore size. Suitable swelling behavior (293 ± 0.05 %) and adequate degradation rates were also approved by characterizing swelling and degradability in vitro. The GT/PLA membrane exhibited a prolonged and sustained SIM release and controlled THY release with high antibacterial efficiency. Cell viability, cell attachment assay, and nuclear staining using 4′,6-diamidino-2-phenylindole (DAPI) showed that the designed GT/PLA substrate had good biocompatibility and cell attachment. Cell infiltration testing also showed that the cells were finely prevented by the outer layer (GT/THY). Overall, the obtained results in this study indicated the great potential of the prepared GT/PLA for use as a GBR which can develop osteogenic and antibacterial biomimetic periosteum optimizing the clinical application of GBR strategies.

An Asymmetric Microfluidic/Chitosan Device for Sustained Drug Release in Guided Bone Regeneration Applications.

One of the major challenges of guided bone regeneration (GBR) is infections caused by pathogen colonization at wound sites. In this paper, an asymmetric microfluidic/chitosan device was developed to release drugs to inhibit infections and to ensure that guided bone regeneration can be realized. The microfluidic technique was introduced into the GBR membrane for the first time, which demonstrated more controllable drug release, more flexible clinical use and had a lower cost compared with surface treatments and embedded nanoparticles. Based on the theory of diffusion and Fick’s first law, the contact area and concentration gradient were adjusted to realize sustained drug release. The standard deviation of minocycline release over 5 days was only 12.7%, which was lower than the joint effect of porous chitosan discs and nanospheres. The in vitro experiments against E. coli and Streptococcus mutans showed the excellent antibacterial performance of the device (>95%). The in vitro experiments for fibroblasts at the microfluidic side and osteoblasts at the chitosan side showed the satisfactory biocompatibility and the ability of the device to enhance bone regeneration. Therefore, this microfluidic/chitosan device is a promising therapeutic approach to prevent infection and guide bone regeneration.

In-situ mineralized homogeneous collagen-based scaffolds for potential guided bone regeneration

For guided bone regeneration (GBR) in clinical orthopedics, the importance of a suitable scaffold which can provide the space needed for bone regeneration and simultaneously promotes the new bone formation cannot be overemphasized. Due to its excellent biocompatibility, mechanical strength, and similarity in structure and composition to natural bone, the mineralized collagen-based scaffolds have been increasingly considered as promising GBR scaffolds. Herein, we propose a novel method to fabricate an in-situ mineralized homogeneous collagen-based scaffold (IMHCS) with excellent osteogenic capability for GBR by electrospinning the collagen solution in combination with essential mineral ions. The IMHCS exhibited homogeneous distribution of apatite crystals in electrospun fibers, which helped to achieve a significantly higher tensile strength than the pure collagen scaffold (CS) and the scaffold with directly added nano-hydroxyapatite particles (HAS). Furthermore, the IMHCS had significantly better cell compatibility, cell migration ratio, and osteogenic differentiation property than the HAS and CS. Therefore, the IMHCS not only retains traditional function of inhibiting fibroblast invasion, but also possesses excellent osteogenic differentiation property, indicating a robust alternative for GBR applications.

Novel Mg-Ca-La alloys for guided bone regeneration: Mechanical performance, stress corrosion behavior and biocompatibility

Guided bone regeneration (GBR) is a therapeutic method that is used to augment deficient ridges before dental implantation. The non-absorbable membranes need secondary removal surgery, while absorbable collagen membranes fail while being applied to large bone defects because of their relatively low stiffness. The “ideal” membrane for use in GBR has yet to be developed. This study aims to develop and explore the feasibility of Mg-Ca-La alloys for application in GBR. Mg-0.2Ca-0.2La alloy exhibits fine microstructure and a good combination of tensile strength and ductility. Mg-0.2Ca-0.2La alloy is also capable of supporting the adhesion, proliferation and migration of human gingival fibroblasts, and shows good cytocompatibility on MC3T3-E1 cells. The GBR membranes usually need intraoperative bending or shaping to adapt the alveolar ridge. The additional effect of bending stress on magnesium-based materials must be considered due to a well-known issue, namely stress-corrosion cracking (SCC). The SCC results reveal that the bended Mg-0.2Ca-0.2La presents a uniform corrosion morphology with a corrosion rate of 0.09 mm/yr, which is 61% less than that of unstressed ones. Mg-0.2Ca-0.2La alloy possesses adequate strength and ductility, high biocompatibility and slow degradation under bending stress, contributing to adequate malleability and sustained spatial stability for membrane use.

3D-printed bi-layered polymer/hydrogel construct for interfacial tissue regeneration in a canine model

ObjectivesThere are complications in applying regenerative strategies at the interface of hard and soft tissues due to the limited designs of constructs that can accommodate different cell types in different sites. The problem originates from the challenges in the adhesion of dissimilar materials, such as polymers and hydrogels, that can be suitable for regenerating different tissues such as bone and soft tissues. This paper presents a design of a new hybrid construct in which a polymer (polycaprolactone (PCL)) membrane firmly adheres to a layer of hydrogen (gelatin). MethodsPCL membranes with defined size and porosity were fabricated using 3D printing. The gelatin layer was attached to the PCL membranes using the aminolysis procedure. We have examined this construct for the application of Guided Bone Regeneration (GBR) as a typical surgical regenerative procedure of the oral cavity at the interface of bone and soft tissue. Complete in vitro and in vivo investigations on canine tibia bone defects have been performed. Histological analyses for fibrosis morphometric and bone morphometric evaluation, as well as bone-fibrosis histological grading and CBCT imaging, were conducted. ResultsChemical and morphological studies of the membrane proved that gelatin was uniformly attached to the aminolyzed PCL membranes. The in vitro and in vivo studies indicated the membrane's biocompatibility, mechanical stability, and barrier function for the GBR application. Furthermore, in vitro study showed that the membranes could improve osteogenesis and the regeneration of bone defects. The results illustrated that the mean bone density in the membrane groups was about three times more than that of the control group. SignificanceThe fabricated 3D-printed hybrid Gelatin/PCL bi-layered membrane can be a good candidate for interfacial tissue engineering and a promising membrane for GBR procedure.

Single-Walled Carbon Nanotube Membranes Accelerate Active Osteogenesis in Bone Defects: Potential of Guided Bone Regeneration Membranes.

Carbon nanotubes (CNTs) are potentially important biomaterials because of their chemical, physical, and biological properties. Our research indicates that CNTs exhibit high compatibility with bone tissue. The guided bone regeneration (GBR) technique is commonly applied to reconstruct alveolar bone and treat peri-implant bone defects. In GBR, bone defects are covered with a barrier membrane to prevent the entry of nonosteogenic cells such as epithelial cells and fibroblasts. The barrier membrane also maintains a space for new bone formation. However, the mechanical and biological properties of materials previously used in clinical practice sometimes delayed bone regeneration. In this study, we developed a CNT-based membrane for GBR exhibiting high strength to provide a space for bone formation and provide cellular shielding to induce osteogenesis. The CNT membrane was made via the dispersion of single-walled CNTs (SWCNTs) in hyaluronic acid solution followed by filtration. The CNT membrane assumed a nanostructure surface due to the bundled SWCNTs and exhibited high strength and hydrophilicity after oxidation. In addition, the membrane promoted the proliferation of osteoblasts but not nonosteogenic cells. CNT membranes were used to cover experimental bone defects made in rat calvaria. At 8 weeks after surgery, more extensive bone formation was observed in membrane-covered defects compared with bone defects not covered with membrane. Almost no diffusion of CNTs was observed around the membrane. These results indicate that the CNT membrane has adequate strength, stability, and surface characteristics for osteoblasts, and its shielding properties promote bone formation. Demonstration of the safety and osteogenic potential of the CNT membranes through further animal studies should facilitate their clinical application in GBR.

Differently Charged P (VDF-TrFE) Membranes Influence Osteogenesis Through Differential Immunomodulatory Function of Macrophages

A biomaterial-mediated immune response is a critical factor to determine the cell fate as well as the tissue-regenerative outcome. Although piezoelectric-membranes have attracted considerable interest in the field of guided bone regeneration thanks to their biomimetic electroactivity, the influence of their different surface-charge polarities on the immune-osteogenic microenvironment remains obscure. The present study aimed at investigating the interaction between piezoelectric poly (vinylidene fluoridetrifluoroethylene) [P (VDF-TrFE)] membranes with different surface polarities (negative or positive) and macrophage response, as well as their subsequent influence on osteogenesis from an immunomodulating perspective. Specifically, the morphology, wettability, crystal phase, piezoelectric performance, and surface potential of the synthetic P (VDF-TrFE) samples were systematically characterized. In addition, RAW 264.7 macrophages were seeded onto differently charged P (VDF-TrFE) surfaces, and the culture supernatants were used to supplement cultures of rat bone marrow mesenchymal stem cells (rBMSCs) on the corresponding P (VDF-TrFE) surfaces. Our results revealed that oppositely charged surfaces had different abilities in modulating the macrophage-immune-osteogenic microenvironment. Negatively charged P (VDF-TrFE), characterized by the highest macrophage elongation effect, induced a switch in the phenotype of macrophages from M0 (inactivated) to M2 (anti-inflammatory), thus promoting the osteogenic differentiation of rBMSCs by releasing anti-inflammatory cytokine IL-10. Interestingly, positively charged P (VDF-TrFE) possessed pro-inflammatory properties to induce an M1 (pro-inflammatory) macrophage-dominated reaction, without compromising the subsequent osteogenesis as expected. In conclusion, these findings highlighted the distinct modulatory effect of piezoelectric-P (VDF-TrFE) membranes on the macrophage phenotype, inflammatory reaction, and consequent immune-osteogenic microenvironment depending on their surface-charge polarity. This study provides significant insight into the design of effective immunoregulatory materials for the guided bone regeneration application.