Zn-containing Adhesives Facilitate Collagen Protection and Remineralization at the Resin-Dentin Interface: A Narrative Review.

This is a narrative review of the literature assessing the potential effectiveness of doping dentin polymeric adhesives with zinc compounds in order to improve bonding efficacy, remineralization and protection against degradation. A literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI and Web of Science. Through our search, we found literature demonstrating that Zn-doped dentin adhesives promote protection and remineralization of the resin-dentin interfaces. The increased bioactivity has also facilitated dentinal tubules' occlusion by crystals' precipitation contributing to improved sealing efficacy of restorations. Loading dentin adhesives with zinc gives rise to an increase of both crystallinity of mineral and crosslinking of collagen. The main role of zinc, in dentin adhesives, is to inhibit collagen proteolysis. We concluded that zinc exerts a protective effect through binding at the collagen-sensitive cleavage sites of matrix-metalloproteinases (MMPs), contributing to dentin matrix stabilization. Zinc may not only act as a MMPs inhibitor, but also influence signaling pathways and stimulate metabolic effects in dentin mineralization and remineralization processes. Zn-doped adhesives increase the longevity of dentin bonding through MMPs inhibition. Zn poses a remineralization strategy in demineralized dentin.

Protein adsorption and bioactivity of functionalized electrospun membranes for bone regeneration.

OBJECTIVES: To evaluate the adsorption of bone related proteins and bioactivity of experimental functionalized (carboxylated or aminated) polymeric membranes for bone regeneration. METHODS: Polymethylmethacrylate-based membranes functionalized with carboxyl or amino radicals were tested. Membranes were zinc loaded and the adsorption isotherms of zinc were studied. Human plasma proteins, bovine serum albumin, fibrinogen and fibronectin adsorption were measured with a spectrophotometer applying an acid determination protocol. Biomimetic calcium phosphate precipitation on polymeric membranes was also assessed after simulated body fluid immersion. Scanning electron microscopy and elemental analysis by means of an energy dispersive system were used for mineral deposits identification. A commercially available polytetrafluoroethylene membrane was used as control. RESULTS: Both experimental membranes produced higher protein adsorption than the commercial control that does not adsorb proteins. Carboxylated membranes adsorbed significantly more albumin than the aminated ones, the opposite occurred with fibrinogen. With plasma and fibronectin proteins both type of membranes performed similarly. Only carboxylated membranes were bioactive and precipitated calcium and phosphate on their surfaces. CONCLUSIONS: The polymethylmethacrylate zinc-loaded membranes functionalized with carboxyl groups performed as high adsorbable membranes for bone regeneration related proteins. They also served as templates for mineralization of hydroxyapatite. CLINICAL SIGNIFICANCE: Protein adsorption is the initial reaction after the implantation of a biomaterial into the body and will influence subsequent cell function. The adsorption of bone related proteins together with the observed biomimetic calcium deposition on the experimental carboxylated membranes could be associated with their ability to promote bone regeneration.

State of the Art on Biomaterials for Soft Tissue Augmentation in the Oral Cavity. Part II: Synthetic Polymers-Based Biomaterials.

Most of the polymers used as biomaterials for scaffolds are naturally occurring, synthetic biodegradable, and synthetic non-biodegradable polymers. Since synthetic polymers can be adapted for obtaining singular desired characteristics by applying various fabrication techniques, their use has increased in the biomedical field, in dentistry in particular. The manufacturing methods of these new structures include many processes, such as electrospinning, 3D printing, or the use of computer-aided design/computer-aided manufacturing (CAD/CAM). Synthetic polymers show several drawbacks that can limit their use in clinical applications, such as the lack of cellular recognition, biodegradability, and biocompatibility. Moreover, concerning biodegradable polymers, the time for matrix resorption is not predictable, and non-resorbable matrices are preferred for soft tissue augmentation in the oral cavity. This review aimed to determine a new biomaterial to offset the present shortcomings in the oral environment. Researchers have recently proposed a novel non-resorbable composite membrane manufactured via electrospinning that has allowed obtaining remarkable in vivo outcomes concerning angiogenesis and immunomodulation throughout the polarization of macrophages. A prototype of the protocol for in vitro and in vivo experimentation with hydrogels is explained in order to encourage innovation into the development of promising biomaterials for soft tissue augmentation in the near future.

State of the Art on Biomaterials for Soft Tissue Augmentation in the Oral Cavity. Part I: Natural Polymers-Based Biomaterials.

Oral soft tissue thickening or grafting procedures are often necessary to cover tooth recession, re-establish an adequate width of keratinized tissue, correct mucogingival deformities improving esthetics, prepare a site for an implant or prosthetics, for ridge preservation procedures, and soft tissue contouring around dental implants. Gingival recession and root or implant exposure are commonly associated and have led to mucogingival deficiencies that have traditionally been treated with free gingival grafts and autogenous soft tissue grafts. The latter represents the gold standard in acquiring a functionally adequate zone of keratinized attached gingiva. However, soft tissue substitutes are more usually employed because they lessen morbidity and abbreviate surgical time. This review is aimed at assessing oral soft tissue augmentation techniques and biomaterials used from existing literature, principally concerning scaffolds from both human and animal-based tissue derivatives matrices. In order to avoid the use of human donor tissue, the xenogenic collagen matrices are proposed for soft tissue augmentation. In general, all of them have provided the remodeling processes and enhanced the formation of new connective tissue within the matrix body.

Doxycycline and Zinc Loaded Silica-Nanofibrous Polymers as Biomaterials for Bone Regeneration.

The main target of bone tissue engineering is to design biomaterials that support bone regeneration and vascularization. Nanostructured membranes of (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 loaded with 5% wt of SiO2-nanoparticles (HOOC-Si-Membrane) were doped with zinc (Zn-HOOC-Si-Membrane) or doxycycline (Dox-HOOC-Si-Membrane). Critical bone defects were effectuated on six New Zealand-bred rabbit skulls and covered with the membranes. After six weeks, the bone architecture was evaluated with micro computed tomography. Three histological analyses were utilized to analyse bone regeneration, including von Kossa silver nitrate, toluidine blue and fluorescence. All membrane-treated defects exhibited higher number of osteocytes and bone perimeter than the control group without the membrane. Zn-HOOC-Si-Membranes induced higher new bone and osteoid area than those treated with HOOC-Si-Membranes, and control group, respectively. Zn-HOOC-Si-Membranes and Dox-HOOC-Si-Membranes attained the lowest ratio M1 macrophages/M2 macrophages. Dox-HOOC-Si-Membranes caused the lowest number of osteoclasts, and bone density. At the trabecular new bone, Zn-HOOC-Si-Membranes produced the highest angiogenesis, bone thickness, connectivity, junctions and branches. Zn-HOOC-Si-Membranes enhanced biological activity, attained a balanced remodeling, and achieved the greatest regenerative efficiency after osteogenesis and angiogenesis assessments. The bone-integrated Zn-HOOC-Si-Membranes can be considered as bioactive modulators provoking a M2 macrophages (pro-healing cells) increase, being a potential biomaterial for promoting bone repair.

Ex vivo investigations on bioinspired electrospun membranes as potential biomaterials for bone regeneration.

OBJECTIVES: To assess the surface characteristics and composition that may enhance osteoblasts viability on novel electrospun composite membranes (organic polymer/silicon dioxide nanoparticles). METHODS: Membranes are composed by a novel polymer blend, the mixture of two hydrophilic copolymers 2-hydroxyethylmethacrylate-co-methylmethacrylate and 2-hydroxyethylacrylate-co-methylacrylate, and they are doped with silicon dioxide nanoparticles. Then the membranes were functionalized with zinc or doxycycline. The membranes were morphologically characterized by atomic force and scanning electron microscopy (FESEM), and mechanically probed using a nanoindenter. Biomimetic calcium phosphate precipitation on polymeric tissues was assessed. Cell viability tests were performed using human osteosarcoma cells. Cells morphology was also studied by FESEM. Data were analyzed by ANOVA, Student-Newman-Keuls and Student t tests (p < 0.05). RESULTS: Silica doping of membranes enhanced bioactivity and increased mechanical properties. Membranes morphology and mechanical properties were similar to those of trabecular bone. Zinc and doxycycline doping did not exert changes but it increased novel membranes bioactivity. Membranes were found to permit osteoblasts proliferation. Silica-doping favored cells proliferation and spreading. As soon as 24 h after the seeding, cells in silica-doped membranes were firmly attached to experimental tissues trough filopodia, connected to each other. The cells produced collagen and minerals onto the surfaces. CONCLUSIONS: Silica nanoparticles enhanced surface properties and osteoblasts viability on electrospun membranes. CLINICAL SIGNIFICANCE: The ability of silica-doped matrices to promote precipitation of calcium phosphate, together with their mechanical properties, observed non-toxicity, stimulating effect on osteoblasts and its surface chemistry allowing covalent binding of proteins, offer a potential strategy for bone regeneration applications.

Polymeric nanoparticles for endodontic therapy.

The effectiveness of novel polymeric nanoparticles (NPs) application in reducing dentin permeability and facilitating dentin remineralization after endodontic treatment was evaluated. The effect of undoped NPs, zinc, calcium and doxycycline-doped NPs (Zn-NPs, Ca-NPs and D-NPs, respectively) was tested in radicular dentin. A control group without NPs was included. Radicular dentin was assessed for fluid filtration. Dentin remineralization was analyzed by scanning and transmission electron microscopy, energy-dispersive analysis, AFM, Young's modulus (Ei), Nano DMA, Raman, and X-Ray Diffraction analysis. Ca-NPs and Zn-NPs treated dentin exhibited the lowest microleakage with hermetically sealed dentinal tubules and a zinc-based salt generation onto dentin. Zn-NPs favored crystallinity and promoted the highest Ei and functional remineralization at the apical dentin, generating differences between the values of complex modulus among groups. Ca-NPs produced closure of tubules and porosities at the expense of a relative mineral amorphization, without creating zones of stress concentration. The highest sealing efficacy was obtained in Zn-NPs-treated samples, along with the highest values of Young's modulus and dentin mineralization. These high values of Ei were obtained by closing voids, cracks, pores and tubules, and by strengthening the root dentin. When using undoped NPs or Ca-NPs, deposition of minerals occurred, but radicular dentin was not mechanically reinforced. Therefore, application of Zn-NPs in endodontically treated teeth previous to the canal filling is encouraged.