Guided Bone Regeneration Treatment Research Articles

An injectable gel based on photo-cross-linkable hyaluronic acid and mesoporous bioactive glass nanoparticles for periodontitis treatment

Guided bone regeneration (GBR) is an effective strategy to promote periodontal tissue repair. The current study aimed to develop an injectable gel for GBR, composed of photo-cross-linkable hyaluronic acid and mesoporous bioactive glass nanoparticles (MBGNs) loaded with antibacterial minocycline hydrochloride (MNCl). Hyaluronic acid modified with methacrylic anhydride (MHA) that could be cross-linked under UV irradiation was first synthesized. Dynamic rheological evaluation of MHA under UV was carried out to determine its in-situ gelling feasibility and stability. Morphological and mechanical characterization was performed to determine the optimal concentration of MHA gels. Sol-gel derived MBGNs loaded with MNCl were further incorporated into MHA gels to obtain the injectable drug-loaded MBGN-MNCl/MHA gels. In vitro antibacterial, anti-inflammatory and osteogenic effects of this gel were evaluated. It was shown that the MHA gel obtained from 3 % MHA under UV treatment of 30s exhibited a suitable porous structure with a compressive strength of 100 kPa. MBGNs with particle size of ∼120 nm and mesopores were confirmed by TEM and SEM. MBGNs had a loading capacity of ∼120 mg/g for MNCl, exhibiting a sustained release behavior. The MBGN-MNCl/MHA gel was shown to effectively inhibit the proliferation of Streptococcus mutans and the expression of pro-inflammatory factors IL-6 and TNF-α by macrophages. It could on the other hand significantly promote the expression of osteogenic-related genes ALP, Runx2, OPN, and osterix of MC3T3-E1 cells. In conclusion, the current design using photo-crosslinkable MHA gel embedded with MNCl loaded MBGNs can serve as a promising injectable formulation for GBR treatment of irregular periodontal defects.

Decellularized periosteum promotes guided bone regeneration via manipulation of macrophage polarization.

Periosteum has shown potential as an effective barrier membrane for guided bone regeneration (GBR). However, if recognized as a "foreign body," insertion of a barrier membrane in GBR treatment will inevitably alter the local immune microenvironment and subsequently influence bone regeneration. The aim of this investigation was to fabricate decellularized periosteum (DP) and investigate its immunomodulatory properties in GBR. DP was successfully fabricated from periosteum from the mini-pig cranium. In vitro experiments indicated that the DP scaffold modulated macrophage polarization toward a pro-regenerative M2 phenotype, which in turn facilitated migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. A rat GBR model with a cranial critical-size defect was established, and our in vivo experiment confirmed the beneficial effects of DP on the local immune microenvironment and bone regeneration. Collectively, the findings of this study indicate that the prepared DP possesses immunomodulatory properties and represents a promising barrier membrane for GBR procedures.

Cell recognitive bioadhesive-based osteogenic barrier coating with localized delivery of bone morphogenetic protein-2 for accelerated guided bone regeneration.

Titanium mesh (Ti-mesh) for guided bone regeneration (GBR) approaches has been extensively considered to offer space maintenance in reconstructing the alveolar ridge within bone defects due to its superb mechanical properties and biocompatibility. However, soft tissue invasion across the pores of the Ti-mesh and intrinsically limited bioactivity of the titanium substrates often hinder satisfactory clinical outcomes in GBR treatments. Here, a cell recognitive osteogenic barrier coating was proposed using a bioengineered mussel adhesive protein (MAP) fused with Alg-Gly-Asp (RGD) peptide to achieve highly accelerated bone regeneration. The fusion bioadhesive MAP-RGD exhibited outstanding performance as a bioactive physical barrier that enabled effective cell occlusion and a prolonged, localized delivery of bone morphogenetic protein-2 (BMP-2). The MAP-RGD@BMP-2 coating promoted in vitro cellular behaviors and osteogenic commitments of mesenchymal stem cells (MSCs) via the synergistic crosstalk effects of the RGD peptide and BMP-2 in a surface-bound manner. The facile gluing of MAP-RGD@BMP-2 onto the Ti-mesh led to a distinguishable acceleration of the in vivo formation of new bone in terms of quantity and maturity in a rat calvarial defect. Hence, our protein-based cell recognitive osteogenic barrier coating can be an excellent therapeutic platform to improve the clinical predictability of GBR treatment.

Biodegradable magnesium barrier membrane used for guided bone regeneration in dental surgery

Barrier membranes are commonly used as part of the dental surgical technique guided bone regeneration (GBR) and are often made of resorbable collagen or non-resorbable materials such as PTFE. While collagen membranes do not provide sufficient mechanical protection of the covered bone defect, titanium reinforced membranes and non-resorbable membranes need to be removed in a second surgery. Thus, biodegradable GBR membranes made of pure magnesium might be an alternative. In this study a biodegradable pure magnesium (99.95%) membrane has been proven to have all of the necessary requirements for an optimal regenerative outcome from both a mechanical and biological perspective. After implantation, the magnesium membrane separates the regenerating bone from the overlying, faster proliferating soft tissue. During the initial healing period, the membrane maintained a barrier function and space provision, whilst retaining the positioning of the bone graft material within the defect space. As the magnesium metal corroded, it formed a salty corrosion layer and local gas cavities, both of which extended the functional lifespan of the membrane barrier capabilities. During the resorption of the magnesium metal and magnesium salts, it was observed that the membrane became surrounded and then replaced by new bone. After the membrane had completely resorbed, only healthy tissue remained. The in vivo performance study demonstrated that the magnesium membrane has a comparable healing response and tissue regeneration to that of a resorbable collagen membrane. Overall, the magnesium membrane demonstrated all of the ideal qualities for a barrier membrane used in GBR treatment.

Fabrication of Polylactic Acid/β-Tricalcium Phosphate FDM 3D Printing Fiber to Enhance Osteoblastic-Like Cell Performance

Guided-bone regeneration (GBR) is increasingly using three-dimensional (3D) printing by fused deposition modeling (FDM) to build the filaments used for treatment. Polylactic acid (PLA) and beta-tricalcium phosphate (β-TCP) are widely used as base materials in 3D printing, necessitating that they are studied together in the context of GBR treatment. This study sought to test and compare the properties and efficacy of different ratios of β-TCP and PLA used to make the 3D-printed filament material to find the most effective combination of materials for GBR treatment. Several ratios of PLA to β-TCP were tested, including PLA/β-TCP ratios of 95%/5% (PLA-5), 90%/10% (PLA-10), 85%/15% (PLA-15), and 80%/20% (PLA-20), and quantitative real-time polymerase chain reaction (qPCR) in vitro testing was done to characterize the material. After adding β-TCP to PLA, mechanical testing indicated that tensile and elongation strengths decreased, hardness was retained, and cell proliferation was promoted. The effect of PLA and β-TCP on increasing alkaline phosphatase (ALP) activity was significantly greater in a ratio of 10% β-TCP/90% PLA at 5 days (p < 0.05) than in any other ratios tested. This is supported by results from qPCR testing, which showed early osteoblast-like differentiation of DLX5, RUNX2, OPG, OC, and collagen type 1 (COL-1) expression levels similar to cells cultured on PLA-10. Our results demonstrated that 3D printing of filaments produced in a ratio of 90% PLA to 10% β-TCP was more effective for GBR than that of filaments produced only using PLA.

Biomimetic Membranes of Methacrylated Gelatin/Nanohydroxyapatite/Poly(l-Lactic Acid) for Enhanced Bone Regeneration.

Nanofibrous poly(l-lactic acid) (PLLA) membrane-simulated extracellular matrices (ECMs) can be used in the biomedical field. However, the hydrophobic nature and poor osteoinductive property of PLLA limit its application in guided bone regeneration (GBR). In this work, a methacrylated gelatin/nano-HA (GelMA/nHA) complex was first synthesized in situ and then introduced into PLLA to fabricate biomimetic GelMA/nHA/PLLA membranes, mimicking the nanofibrous architecture and composition of ECMs by electrospinning and photocrosslinking. Compared to PLLA and GelMA/PLLA membranes, the novel GelMA/nHA/PLLA membranes demonstrated better tensile, hydrophilic, water sorption, and degradation properties. An in vitro biological evaluation indicated that the membranes promoted human bone marrow-derived mesenchymal stem cell (hBMSC) proliferation, adhesion, and osteogenic differentiation. Critical-sized defects in rat models were used to evaluate the bone regeneration performances of the three kinds of membranes in vivo, and the GelMA/nHA/PLLA membranes demonstrated excellent osteogenic regeneration potential. Therefore, GelMA/nHA/PLLA membranes have wide application prospects in bioengineering applications such as GBR treatment.

Using biomimetically mineralized collagen membranes with different surface stiffness to guide regeneration of bone defects.

Because guided bone regeneration (GBR) process is pronouncedly affected by the micro-environment in the defect, the surface stiffness of collagen membranes as a constituent part of the micro-environment was investigated in this study. The objective of this study was to manufacture biomimetically mineralized collagen membranes with controllable surface stiffness based on biomimetic strategy and to investigate the influences of surface stiffness on GBR process. The characterization and biocompatibility of membranes were examined in vitro. The mechanical properties of membranes were evaluated on macro and micro levels using tensile test and atomic force microscope, respectively. The critical-size cranial defect model and ectopic osteogenesis were chosen to employ their performances in vivo. The results indicated that the biomimetically mineralized collagen membranes with controllable surface stiffness were manufactured based on the biomimetic theory. The in vitro experiments showed that the mineralized collagen membrane with satisfactory surface stiffness can better promote the adhesion, proliferation, and osteogenic differentiation of mesenchymal stem cells. The membranes can perform excellently in both osteoinduction and osteoconduction, which results in effective manifestations in aspects of ectopic osteogenesis and GBR in vivo. Therefore, this biomimetically mineralized collagen membrane is a promising candidate for GBR treatment in future.

Long‐Term Follow‐Up on Soft and Hard Tissue Levels Following Guided Bone Regeneration Treatment in Combination with a Xenogeneic Filling Material: A 5‐Year Prospective Clinical Study

In the present prospective study, bone augmentation by guided bone regeneration (GBR) in combination with bovine hydroxyapatite (BHA) as filling material was evaluated with regard to soft and hard tissue stability over time. Implant survival, radiologic bone level (marginal bone level [MBL]), and clinical soft tissue parameters (marginal soft tissue level [MSTL]) were observed. Twenty patients received a total of 41 implants (Brånemark System, Nobel Biocare, Göteborg, Sweden) in conjunction with GBR treatment. The end point of the study was after 5 years following implant placement. The cumulative implant survival rate was 97.5% corresponding to one implant failure. The radiologic evaluation of the MBL demonstrated a crestal bone height above the level of the fixture head. The bone height decreased from -3.51 to -2.38 mm (p < .001). The MSTL was -1.52 mm at baseline and -1.15 mm at the 5-year follow-up (p < .04) demonstrating a stable submucosal crown margin throughout the study period. GBR treatment in combination with a xenogeneic filling material (BHA) is a viable treatment option in order to maintain stable hard and soft tissue levels in conjunction with augmentative procedure related to oral implant treatment.

Effect of diabetes and metabolic control on de novo bone formation following guided bone regeneration

To evaluate histologically and morphometrically the effect of experimental diabetes and metabolic control on de novo bone formation following guided bone regeneration (GBR). Thirty-five Wistar rats were allocated in three experimental groups: (a) uncontrolled, streptozotocin-induced diabetes (D); (b) insulin-controlled diabetes (CD); (c) healthy (H). A standardised titanium microimplant with sandblasted and acid-etched surface was placed into the inferior border of the mandible bilaterally. On the test site, the microimplant was covered with a titanium reinforced expanded polytetrafluoroethylene membrane securely fixed in the mandible according to the GBR principle. The contralateral site served as control. Following 90 days of healing, undecalcified sections were prepared and planimetric measurements of the per cent vertical height of newly formed bone and the per cent new bone-to-implant contact were performed. In all experimental groups, at the GBR treated sites, significant neo-osteogenesis was observed. The vertical height of the newly formed bone and per cent bone-to-implant contact were not statistically significantly different among the H (51.3 + or - 7.2% and 50 + or - 6.8%), D (30.5 + or - 13.4% and 35 + or - 16.8%) and CD (41.6 + or - 8.3% and 39.9 + or - 6.5%) groups. However, uncontrolled diabetes was related to higher outcome variability and increased rate of infectious complications. In the control sites, marginal bone loss was observed in the D group, whereas, in the H and CD groups, minimal new bone formation was observed. Significant de novo bone formation can be achieved via GBR treatment even in the presence of uncontrolled diabetes, although less predictably compared with the healthy status. Insulin-mediated metabolic control may reverse these adverse effects.

New Fabrication Process of Layered Membranes Based on Poly(Lactic Acid) Fibers for Guided Bone Regeneration

A siloxane-containing poly(L-lactic acid) (PLLA)/calcium carbonate (vaterite) hybrid (Si-PVH) shows excellent proliferation of osteoblast-like cells, which may be enhanced by continuously released silicon-species. In the present work a novel membrane for guided bone regeneration (GBR) was developed using Si-PVH. The membrane was composed of bi-layered nonwoven fabrics; the first layer consists of an Si-PVH fabric with large-sized pores for enhancing bone formation, and the second layer consists of a PLLA fabric with small-sized pores for controlling the intrusion of soft tissues and for reinforcing the mechanical strength of the brittle Si-PVH layer. These nonwoven fabrics with high porosities were prepared by an electrospinning method. The PLLA fabric was placed on the Si-PVH one, and then pressed with a stainless steel mesh heated at 150°C, resulting in the preparation of a bi-layered porous membrane with excellent flexibility. The bi-layered membrane was implanted; the Si-PVH fabric was placed in contact with 8 mm in diameter hole drilled in calvaria of 14-week old rabbits and the PLLA fabric was placed in contact with the skin; new bone formation was observed in the Si-PVH layer. The result showed that the PLLA fibers layer interrupted the intrusion of soft tissues and the Si-PVH one induced the bone formation. The bi-layered membrane is expected to be effective in GBR treatment.

Diagnosis and treatment of extraction sockets in preparation for implant placement: report of three cases

This article addresses diagnostic parameters that should be assessed in the treatment of extraction sockets with dental implant placement by presenting three case reports that emphasize the relevance of the amount of remaining bone walls. Diagnosis was based on the analysis of clinical and radiographic parameters (e.g.: bone defect morphology, remaining bone volume, presence of infections on the receptor site). Case 1 presents a 5-wall defect in the maxillary right central incisor region with severe root resorption, which was treated with immediate implant placement. Cases 2 and 3 present, respectively, two- and three-wall bone defects that did not have indication for immediate implants. These cases were first submitted to a guided bone regeneration (GBR) procedure with bone graft biomaterial and membrane barriers, and the implants were installed in a second surgical procedure. The analysis of the preoperative periodontal condition of the adjacent teeth and bone defect morphology is extremely important because these factors determine the choice between immediate implant or GBR treatment followed by implant installation in a subsequent intervention.

Reproducibility and accuracy of automated probe measurements of gingiva and bone levels on stone casts following guided bone regeneration treatment.

For evidence-based evaluation of guided bone regeneration (GBR), accurate registration of changes in gingiva and bone levels is needed. A new method is introduced and evaluated. In a clinical trial with 30 patients, alginate impressions of the surgical area including the interproximal gingiva and alveolar bone at the adjacent teeth were made in duplicate prior to and during GBR surgery, fixture installation and abutment connection. Poured in hard stone, the casts were used for repeated measurements of the level of the free gingival margin and the alveolar bone with an automated probe (Florida disc-probe(R)), using the incisal edge as a fixed reference point. The reproducibility and accuracy of these measurements were evaluated by means of the Intraclass Correlation Coefficients and Generalizability Theory. The effect of treatment was evaluated by multivariate analysis of variance. Generalizability Theory indicated a high accuracy of the gingiva- and bone-level measurements: the Intraclass Correlation Coefficients for gingiva and bone levels were 0.99 and 0.98, respectively. The intra-cast reproducibility was 0.09+/-0.07 mm (mean+/-SD) and the inter-cast reproducibility was 0.10+/-0.09 and 0.20+/-0.07 mm for gingiva and bone levels, respectively. Clinical applicability is demonstrated by the fact that manova revealed on average a small but highly significant (p=0.001) effect of the staged surgical intervention on the gingiva and bone levels at the adjacent teeth. It is concluded that the presented method makes it possible to evaluate reproducibly and accurately changes in gingiva and bone levels for GBR studies.