Recent progress in materials development and biological properties of GTR membranes for periodontal regeneration.

Chronic periodontal is a very common infection that instigates the destruction of oral tissue, and for its treatment, it is necessary to minimize the infection and the defects regeneration. Periodontium consists of four types of tissues: (a) cementum, (b) periodontal ligament, (c) gingiva, and 4) alveolar bone. In separated cavities, regenerative process also allows various cell proliferations. Guided tissue regeneration (GTR) is a potential procedure that favors periodontal regrowth; however, some limitations (such as ineffective hemostatic property, poor mechanical property, and improper biodegradation) are also associated with it. This review mainly emphasizes on the following areas: (a) a summarized overview of the periodontium and its immunological situations, (b) recently utilized treatments for regeneration of distinctive periodontal tissues; (c) an overview of GTR membranes available commercially, and the latest developments on the characterization and processing of GTR membrane material; and 4) the function of the different non-polymeric/polymeric materials, which are acting as drug carriers, antibacterial agents, nanoparticles, and periodontal barrier membranes to prevent periodontal inflammation and to improve the strength of the GTR membrane.

Mussel-inspired antimicrobial coating on PTFE barrier membranes for guided tissue regeneration.

Guided tissue regeneration procedures to treat periodontitis lesions making use of polytetrafluoroethylene (PTFE) membranes exhibit large variability in their surgical outcomes, due to bacterial infection following implantation. This work reports on a facile method to obtain antimicrobial coatings for such PTFE membranes, by exploiting a mussel-inspired approach andin-situformation of silver nanoparticles (AgNPs). PTFE films were initially coated with self-polymerized 3,4-dihydroxy-DL-phenylalanine (DOPA) (PTFE-DOPA), then incubated with AgNO3solution. In the presence of catechol moieties, Ag+ions reduced into Ag0, forming AgNPs of around 68 nm in the polyDOPA coating on PTFE membranes (PTFE-DOPA-Ag). The x-ray photoelectron spectroscopy, atomic force microscopy and scanning electron microscopy analyses indicated that the AgNPs were distributed quite homogeneously in the polymeric membrane. The antimicrobial ability of PTFE-DOPA-Ag membranes againstStaphylococcus aureusandEscherichia coliwas assessed.In vitrocell assay using NIH 3T3 fibroblasts showed that, although cells were adhered to PTFE-DOPA-Ag membranes, their viability and proliferation were limited demonstrating again the antibacterial activities of PTFE-DOPA-Ag membranes. This work provides proof-of-concept study of a new versatile approach for AgNPs coating, which may be easily applied to many other types of polymeric or metallic implants through exploiting the adhesive behavior of mussel-inspired coatings.

Releasing Incisions Using Upward-Motion Scissors Technique for Flap Mobilization for Guided Bone Regeneration or Periodontal Surgery: Technical Introduction and a Case Report.

Flap management is one of the key elements for success in periodontal surgeries and bone regeneration for dental implants. The aim of this article is to introduce a releasing incision method for effective flap advancement to obtain tension-free primary closure. The 'upward-motion scissors technique' (UMST) involves the use of surgical scissors handled with an upward motion to create multiple shallow incisions. The use of UMST is demonstrated in an anatomically challenging case requiring bone augmentation. This technique provides a novel approach for flap advancement and may reduce potential complications involved in releasing incisions. The true benefit of UMST needs to be evaluated in future studies.

The Effect of Implant Abutment Design on Long-Term Soft Tissue Stability: A Clinical Case Report.

Prosthetic rehabilitation of malpositioned anterior dental implants can be challenging. Interdisciplinary treatment planning and precise execution of biologically acceptable prosthetic and surgical protocols are essential to achieve optimal esthetic results and while avoiding and managing esthetic complications. This case study focuses on the restorative aspect. Two sets of custom gold abutments were used prior to and following surgical correction of a pre-existing soft and hard tissue ridge defect surrounding maxillary central incisor implant restorations. A stable and esthetically pleasing result was documented 7 years following delivery of definitive esthetic central incisor implant restorations.

Development of layered PLGA membranes for periodontal tissue regeneration.

OBJECTIVE: Various commercial products are available for guided tissue regeneration (GTR) therapy; however, they do not combine biosafety with the ability to control cell function. The purpose of this study was to evaluate the physicochemical and biological characteristics of the novel bilayer biodegradable poly(lactic-co-glycolic acid) (PLGA) membrane, and to assess whether the bilayer PLGA membrane could be used for periodontal tissue regeneration. METHODS: Bilayer biodegradable membrane was fabricated thorough a two-step freezing and lyophilization process using PLGA solution. The characteristics of bilayer membranes were evaluated with respect to surface morphology, stability, mechanical strength, and operability for clinical use. Cell proliferation and osteogenic differentiation were investigated on the each surface of bilayer membrane. Then, these membranes were implanted to the rat calvaria bone defect models and evaluated their capability for tissue regeneration. RESULTS: Biodegradable membranes composed of the solid and porous layer were successfully prepared and the surface morphologies analyzed. Physicochemical analyses revealed that the membranes possessed enough stability and mechanical properties for clinical use. It was also confirmed that the solid layer inhibited cell proliferation and subsequent connective tissue invasion, while the inner layer promoted proliferation and osteogenic differentiation, thus resulting in bone regeneration in vivo. SIGNIFICANCE: The layering technology used to fabricate the bilayer polymer membrane could be applied in the developing of other novel biomaterials. The present study demonstrates that the bilayer biodegradable polymer membranes facilitate tissue regeneration in vivo, and therefore represent a prospective biomaterial for GTR therapy.

ESR investigations of gamma irradiated medical devices.

Guided tissue regeneration (GTR) and guided bone regeneration (GBR) biomaterials have been employed in recent years for periodontal procedures. In the present study, widely used dental GTR/GBR biomaterials (grafts: G1, G2, G3 and membranes: M1, M2, M3, M4) were exposed to gamma irradiation at an absorbed dose range of 0-50kGy and the radiolytic intermediates that have been created in the samples upon irradiation were characterized in detail by Electron Spin Resonance (ESR) spectroscopy. We aimed to standardize the measurement conditions for practical applications of gamma radiation sterilization of GTR/GBR biomaterials. We investigated the characteristic features of free radicals in gamma irradiated GTR/GBR biomaterials and examined the stability of the induced radicals at room temperature and accelerated stability conditions with ESR spectroscopy including dose-response curves, microwave power studies, dosimetric features of the biomaterials, variations of the peak heights with temperature, and long term stabilities of the radical species. Long-term stability studies have shown that G1 is quite stable even in accelerated storage conditions. The signal intensities of graft-type GTR/GBR biomaterials stored in normal and stability conditions have decreased very rapidly even only a few days after gamma irradiation sterilization. Thus, those samples indicating relatively low stability features can be very good candidates for the radiosterilization process. The beta-tricalcium phosphate and PLGA containing G1 and M1 respectively have found to be the most gamma stable bone substitute biomaterials and be safely sterilized by gamma radiation. ESR spectroscopy is an appropriate technique in giving important detailed spectroscopic findings in the gamma radiation sterilization studies of GTR/GBR biomaterials.

Videoscope Assisted Minimally Invasive Surgery (VMIS): 36-Month Results.

BACKGROUND: Clinical outcomes from videoscope assisted minimally invasive surgery (VMIS) at 36 to 58 months are reported. METHODS: Fourteen patients having sites with residual probing depth (PD) of at least 5 mm and 2 mm loss of clinical attachment level (CAL) after initial non-surgical therapy were treated with VMIS. RESULTS: At 36 months or greater post-surgery there was a statistically significant improvement (P <0.001) in mean PD and CAL (PD: 3.80 ± 1.18 mm, CAL: 4.16 ± 1.18 mm) in all surgical sites compared with baseline. There was a mean improvement in soft tissue height (0.36 ± 0.64 mm, P = 0.03). In most cases, patients reported no postoperative discomfort. CONCLUSIONS: Improvements from VMIS appear to be favorable when compared with previously reported results of periodontal regenerative surgery. All improvements were stable over time. The lack of post-surgical recession after VMIS has not been reported with traditional regenerative surgery.

Limitations and options using resorbable versus nonresorbable membranes for successful guided bone regeneration.

OBJECTIVE: Deficient bony ridges often complicate the implant treatment plan. Several treatment modalities are used to regenerate bone, including guided bone regeneration (GBR). The purpose of this study was to summarize the knowledge on different types of membranes available and currently used in GBR procedures in a staged approach or with simultaneous implant placement. The primary role of the membranes is to exclude epithelial and connective tissue cells from the wound area to be regenerated, and to create and maintain the space into which pluripotential and osteogenic cells are free to migrate. DATA SOURCES: A literature search was performed for articles that were published in English on the topic. A selected number of studies were chosen in order to provide a review of the main characteristics, applications, and outcomes of the different types of membranes. Resorbable membranes are made of natural or synthetic polymers like collagen and aliphatic polyesters. Collagens are the most common type used. They have similar collagen composition to the periodontal connective tissue. Other materials available include human, porcine, and bovine pericardium membranes, human amnion and chorion tissue, and human acellular freeze-dried dermal matrix. Nonresorbable membranes used in GBR include dense-polytetrafluoroethylene (d-PTFE), expanded-polytetrafluoroethylene (e-PTFE), titanium mesh, and titanium-reinforced polytetrafluoroethylene. CONCLUSIONS: The most common complication of nonresorbable membranes is exposure, which has detrimental effect on the final outcome with both types of membranes. For vertical bone augmentation procedures, the most appropriate membranes are the nonresorbable. For combination defects, both types result in a successful outcome.

Guided bone regeneration in distal mandibular atrophy by means of a preformed titanium foil: a case series.

The aim of this case series was to evaluate the clinical outcome of preformed titanium foil (PTF) to perform guided bone regeneration (GBR) in posterior mandibular atrophies. Thirteen patients (4 male; 9 female; mean age 58.85±10.16 years), with class II division C atrophy, according to Misch, were selected to perform GBR by means of PTF, using a moldable allograft paste as graft material. The devices, made of a 0.2mm thick pure titanium foil, were pre-shaped using stereolithographic models obtained from CT-scan of the patients’ recipient sites. In the second stage, performed at 6.35±2.15 months, 23 cylindrical two-piece implants were placed and the devices removed. At four months, the implants were exposed and submitted to progressive prosthetic load for a span of 4 months. The cases were finalized by means of metal-ceramic cementable restorations. The post finalization follow-up was at 12 months. Survival rate (i.e. SVR) was 100% since no fixtures were lost. At the one-year follow up, the clinical appearance of the soft tissues was optimal and no pathological signs on probing were recorded. The success rate (i.e. SCR) was 82.6% and the average peri-implant bone reabsorption was 0.99±0.59 mm. The results suggest good potentialities of this method for bone volume augmentation in distal mandibular atrophies, allowing to maximize the outcome and simplifying the surgical phase.

Periodontal regeneration with stem cells-seeded collagen-hydroxyapatite scaffold.

Re-establishing compromised periodontium to its original structure, properties and function is demanding, but also challenging, for successful orthodontic treatment. In this study, the periodontal regeneration capability of collagen-hydroxyapatite scaffolds, seeded with bone marrow stem cells, was investigated in a canine labial alveolar bone defect model. Bone marrow stem cells were isolated, expanded and characterized. Porous collagen-hydroxyapatite scaffold and cross-linked collagen-hydroxyapatite scaffold were prepared. Attachment, migration, proliferation and morphology of bone marrow stem cells, co-cultured with porous collagen-hydroxyapatite or cross-linked collagen-hydroxyapatite, were evaluated in vitro. The periodontal regeneration capability of collagen-hydroxyapatite scaffold with or without bone marrow stem cells was tested in six beagle dogs, with each dog carrying one sham-operated site as healthy control, and three labial alveolar bone defects untreated to allow natural healing, treated with bone marrow stem cells - collagen-hydroxyapatite scaffold implant or collagen-hydroxyapatite scaffold implant, respectively. Animals were euthanized at 3 and 6 months (3 animals per group) after implantation and the resected maxillary and mandibular segments were examined using micro-computed tomography scan, H&E staining, Masson's staining and histometric evaluation. Bone marrow stem cells were successfully isolated and demonstrated self-renewal and multi-potency in vitro. The porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite had average pore sizes of 415 ± 20 µm and 203 ± 18 µm and porosity of 69 ± 0.5% and 50 ± 0.2%, respectively. The attachment, proliferation and migration of bone marrow stem cells were satisfactory on both porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite scaffolds. Implantation of bone marrow stem cells - collagen-hydroxyapatite or collagen-hydroxyapatite scaffold in beagle dogs with experimental periodontal defects resulted in significantly enhanced periodontal regeneration characterized by formation of new bone, periodontal ligament and cementum, compared with the untreated defects, as evidenced by histological and micro-computed tomography examinations. The prepared collagen-hydroxyapatite scaffolds possess favorable bio-compatibility. The bone marrow stem cells - collagen-hydroxyapatite and collagen-hydroxyapatite scaffold - induced periodontal regeneration, with no aberrant events complicating the regenerative process. Further research is necessary to improve the bone marrow stem cells behavior in collagen-hydroxyapatite scaffolds after implantation.

Sol-gel processing of novel bioactive Mg-containing silicate scaffolds for alveolar bone regeneration.

Periodontal tissue regeneration is an important application area of biomaterials, given the large proportion of the population affected by periodontal diseases like periodontitis. The aim of this study was the synthesis of a novel porous bioceramic scaffold in the SiO2-CaO-MgO system with specific properties targeted for alveolar bone tissue regeneration using a modification of the traditional foam replica technique. Since bioceramic scaffolds are considered brittle, scaffolds were also coated with gelatin in order to increase their mechanical stability. Gelatin was chosen for its biocompatibility, biodegradability, low-cost, and low immunogenicity. However, gelatin degrades very fast in water solutions. For this reason, two different cross-linking agents were evaluated. Genipin, a non-toxic gardenia extract and the chemical compound 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) in combination with N-hydroxysuccinimide (NHS), which is also considered non-toxic. The results of the investigation indicated that all scaffolds presented an open, interconnected porosity and pores' sizes in the range of 300-600 µm, fast apatite-forming ability, biocompatibility, and suitable mechanical stability.

Guided Tissue Regeneration in Four Teeth Using a Liquid Polymer Membrane.

Periodontal disease is one of the most common diseases diagnosed in dogs and cats. Guided tissue regeneration (GTR) is a treatment alternative to extraction of strategically important teeth. The barrier membrane used in the GTR procedure is of key importance. The purpose of this case series was to evaluate a liquid polymer gel as a membrane for GTR. The polymer gel ( N-methyl-2-pyrrolidone and poly [DL-lactide]) combined with 8.5% doxycycline hyclate was used in place of a traditional membrane in 4 teeth. The teeth were re-examined 6 months postoperatively for radiographic evaluation. A decrease in probing depth and new alveolar bone formation was seen 6 months postoperatively. Improvement in periodontal disease stage was seen in 2 of the 4 teeth. Larger controlled trials with histopathologic evaluation are indicated to further assess the use of this polymer as a membrane in GTR. However, the clinical outcomes of all 4 treated teeth were considered successful.

Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges.

Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-ß1 release from PRP incorporated gelatin sponge, amounts of TGF-ß1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5 × PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3 × PRP. In the transplantation, the size of the bone regenerated in the defect with 3 × PRP incorporated gelatin sponge was larger than that of the other group.

Evaluation of the Antibacterial Effect of Silver Nanoparticles on Guided Tissue Regeneration Membrane Colonization--An in Vitro Study.

OBJECTIVE: The aim of this in vitro study was to investigate the colonization and penetration of specific bacteria on nanosilver-impregnated GTR (guided tissue regeneration) membranes. METHODS: Three sets of GTR membranes were used in this study: 1) GTR-C: Plain GTR membrane as a negative control; 2) GTR-NS: GTR membrane impregnated with silver nanoparticles as the test group; 3) GTR-DOX: GTR membrane impregnated with 25% (w/w) doxycycline hydrochloride acting as a positive control. Stress-strain characteristics were calculated to determine the physical properties of the control and impregnated membranes. Qualitative observation of microbial adherence and bacterial penetration through GTR membranes were performed by using four organisms (Streptococcus mutans, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Porphyromonas gingivalis) reported to have strong adherent capabilities to collagen membranes. RESULTS: The mean bacterial adherence scores were significantly greater (p < 0.001) in the GTR-C group when compared to GTR-DOX and GTR-NS groups. GTR-NS showed lower adherence scores than GTR-DOX across all four microorganisms; this difference, however was not statistically significant. The difference in colony forming units (CFUs) was highly significant (p < 0.001), suggesting greater penetration in GTR-C membranes when compared to GTR-NS and GTR-DOX groups. Though the mean CFUs were lower in GTR-DOX than in GTR-NS across all four microorganisms, this difference was statistically significant only for S. mutans and F. nucleatum. CONCLUSION: The incorporation of silver nanoparticles may be of value when controlling membrane-associated infection. Studies with different nanosilver particle sizes should be conducted to further evaluate the beneficial properties of nanosilver against periodontal pathogens.

Membranes for Periodontal Regeneration--A Materials Perspective.

Periodontitis is a chronic inflammatory disorder affecting nearly 50% of adults in the United States. If left untreated, it can lead to the destruction of both soft and mineralized tissues that constitute the periodontium. Clinical management, including but not limited to flap debridement and/or curettage, as well as regenerative-based strategies with periodontal membranes associated or not with grafting materials, has been used with distinct levels of success. Unquestionably, no single implantable biomaterial can consistently guide the coordinated growth and development of multiple tissue types, especially in very large periodontal defects. With the global aging population, it is extremely important to find novel biomaterials, particularly bioactive membranes and/or scaffolds, for guided tissue (GTR) and bone regeneration (GBR) to aid in the reestablishment of the health and function of distinct periodontal tissues. This chapter offers an update on the evolution of biomaterials (i.e. membranes and bioactive scaffolds) as well as material-based strategies applied in periodontal regeneration. The authors start by providing a brief summary of the histological characteristics and functions of the periodontium and its main pathological condition, namely periodontitis. Next, a review of commercially available GTR/GBR membranes is given, followed by a critical appraisal of the most recent advances in the development of bioactive materials that enhance the chance for clinical success of periodontal tissue regeneration.

Freeze gelated porous membranes for periodontal tissue regeneration.

Guided tissue regeneration (GTR) membranes have been used for the management of destructive forms of periodontal disease as a means of aiding regeneration of lost supporting tissues, including the alveolar bone, cementum, gingiva and periodontal ligaments (PDL). Currently available GTR membranes are either non-biodegradable, requiring a second surgery for removal, or biodegradable. The mechanical and biofunctional limitations of currently available membranes result in a limited and unpredictable treatment outcome in terms of periodontal tissue regeneration. In this study, porous membranes of chitosan (CH) were fabricated with or without hydroxyapatite (HA) using the simple technique of freeze gelation (FG) via two different solvents systems, acetic acid (ACa) or ascorbic acid (ASa). The aim was to prepare porous membranes to be used for GTR to improve periodontal regeneration. FG membranes were characterized for ultra-structural morphology, physiochemical properties, water uptake, degradation, mechanical properties, and biocompatibility with mature and progenitor osteogenic cells. Fourier transform infrared (FTIR) spectroscopy confirmed the presence of hydroxyapatite and its interaction with chitosan. µCT analysis showed membranes had 85-77% porosity. Mechanical properties and degradation rate were affected by solvent type and the presence of hydroxyapatite. Culture of human osteosarcoma cells (MG63) and human embryonic stem cell-derived mesenchymal progenitors (hES-MPs) showed that all membranes supported cell proliferation and long term matrix deposition was supported by HA incorporated membranes. These CH and HA composite membranes show their potential use for GTR applications in periodontal lesions and in addition FG membranes could be further tuned to achieve characteristics desirable of a GTR membrane for periodontal regeneration.

Horizontal-guided Bone Regeneration using a Titanium Mesh and an Equine Bone Graft.

AIM: The present work describes a horizontal ridge augmentation in which a titanium mesh was preshaped by adapting it to a stereolithographic model of the patient's jaw that was fabricated from CT scans. BACKGROUND: Guided bone regeneration (GBR) involves covering the augmentation site with a long-lasting barrier to protect it from the invasion of surrounding soft tissues. Among barriers, titanium meshes may provide a successful outcome, but the intraoperatory time needed to shape them is a disadvantage. CASE DESCRIPTION: The 54-year-old patient, missing the right mandibular second bicuspid, first molar, and second molar, had her atrophic ridge augmented with a 30:70 mixture of autogenous bone and equine, enzyme-deantigenic collagen-preserved bone substitute. Two conical implants were inserted concomitantly in the second bicuspid and first molar positions, and the site was protected with the preshaped mesh. Four months later, the titanium mesh was retrieved, a bone sample was collected, and histological and histomorphometric analyses were performed. Provisional and definitive prostheses were then delivered, and follow-up controls were performed for up to 24 months. CONCLUSION: Preshaping the mesh on a model of the patient's mandible shortened the surgical time and enabled faster mesh placement. Two years after surgery, the implants were perfectly functional, and the bone width was stable over time as shown by radiographic controls. Histological analysis of the bone sample showed the heterologous biomaterial to be biocompatible and undergoing advanced remodeling and replacement with newly formed bone. CLINICAL SIGNIFICANCE: Preshaping a titanium mesh over a stereolithographic model of the patient's jaw allowed for a significant reduction of the intraoperative time and may be therefore, advisable in routine practice.

Graded porous polyurethane foam: a potential scaffold for oro-maxillary bone regeneration.

Bone tissue engineering applications demand for biomaterials offering a substrate for cell adhesion, migration, and proliferation, while inferring suitable mechanical properties to the construct. In the present study, polyurethane (PU) foams were synthesized to develop a graded porous material-characterized by a dense shell and a porous core-for the treatment of oro-maxillary bone defects. Foam was synthesized via a one-pot reaction starting from a polyisocyanate and a biocompatible polyester diol, using water as a foaming agent. Different foaming conditions were examined, with the aim of creating a dense/porous functional graded material that would perform at the same time as an osteoconductive scaffold for bone defect regeneration and as a membrane-barrier to gingival tissue ingrowth. The obtained PU was characterized in terms of morphological and mechanical properties. Biocompatibility assessment was performed in combination with bone-marrow-derived human mesenchymal stromal cells (hBMSCs). Our findings confirm that the material is potentially suitable for guided bone regeneration applications.