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To endow an implant surface with enhanced properties to ensure an appropriate seal with the host tissue for inflammation/infection resistance, next-generation bone implant collagen–polyphenol nanolayers were built on conventional titanium surfaces through a multilayer approach. X-ray Photoelectron Spectroscopy (XPS) analysis was performed to investigate the chemical arrangement of molecules within the surface layer and to provide an estimate of their thickness. A short-term (2 and 4 weeks) in vivo test of bone implants in a healthy rabbit model was performed to check possible side effects of the soft surface layer on early phases of osteointegration, leading to secondary stability. Results show the building up of the different nanolayers on top of titanium, resulting in a final composite collagen–polyphenol surface and a layer thickness of about 10 nm. In vivo tests performed on machined and state-of-the-art microrough titanium implants do not show significant differences between coated and uncoated samples, as the surface microroughness remains the main driver of bone-to-implant contact. These results confirm that the surface nanolayer does not interfere with the onset and progression of implant osteointegration and prompt the green light for specific investigations of the potential merits of this bioactive coating as an enhancer of the device/tissue seal. [ABSTRACT FROM AUTHOR]

Background The first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices. We aimed to evaluate the potential of a DNA-reacting surface to aid the retention of both the main clot and small fragments within the thrombectomy device to improve the potential of MT procedures. Methods Device-suitable alloy samples were coated with 15 different compounds and put in contact with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus blood elements in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests to study clot retrieval efficacy and quantify distal emboli using an M1 occlusion model. Results Binding properties of samples coated with all compounds were increased for DNA (≈3-fold) and decreased (≈5-fold) for blood elements, as compared with the bare alloy samples in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced distal emboli during experimental MT of large vessel occlusion in a three-dimensional model. Conclusion Our results suggest that clot retrieval devices coated with DNA-binding compounds can considerably improve the outcome of the MT procedures in stroke patients. [ABSTRACT FROM AUTHOR]

In view of endowing the surface of abutments, a component of titanium dental implant systems, with antioxidant and antimicrobial properties, a surface layer coated with epigallocatechin gallate (EGCg), a polyphenol belonging to the class of flavonoids, was built on titanium samples. To modulate interfacial properties, EGCg was linked either directly to the surface, or after populating the surface with terminally linked polyethyleneglycol (PEG) chains, Mw ~1600 Da. The underlying assumption is that fouling-resistant, highly hydrated PEG chains could reduce non-specific bioadhesion and magnify intrinsic EGCg properties. Treated surfaces were investigated by a panel of surface/interfacial sensitive techniques, to provide chemico–physical characterization of the surface layer and its interfacial environment. Results show: (i) successful EGCg coupling for both approaches; (ii) that both approaches endow the Ti surface with the same antioxidant properties; (iii) that PEG-EGCg coated surfaces are more hydrophilic and show a significantly higher (>50%) interaction force with water. Obtained results build up a rationale basis for evaluation of the merits of finely tuning interfacial properties of polyphenols coated surfaces in biological tests. [ABSTRACT FROM AUTHOR]

An injectable delivery platform for promoting delayed bone healing has been developed by combining a thermosensitive polyurethane-based hydrogel with strontium-substituted mesoporous bioactive glasses (MBG_Sr) for the long-term and localized co-delivery of pro-osteogenic Sr2+ ions and an osteogenesis-enhancing molecule, N-Acetylcysteine (NAC). The incorporation of MBG_Sr microparticles, with a final concentration of 20 mg/mL, did not alter the overall properties of the thermosensitive hydrogel, in terms of sol-to-gel transition at a physiological-like temperature, gelation time, injectability and stability in aqueous environment at 37 °C. In particular, the hydrogel formulations (15% w/v polymer concentration) showed fast gelation in physiological conditions (1 mL underwent complete sol-to-gel transition within 3–5 min at 37 °C) and injectability in a wide range of temperatures (5–37 °C) through different needles (inner diameter in the range 0.4–1.6 mm). In addition, the MBG_Sr embedded into the hydrogel retained their full biocompatibility, and the released concentration of Sr2+ ions were effective in promoting the overexpression of pro-osteogenic genes from SAOS2 osteoblast-like cells. Finally, when incorporated into the hydrogel, the MBG_Sr loaded with NAC maintained their release properties, showing a sustained ion/drug co-delivery along 7 days, at variance with the MBG particles as such, showing a strong burst release in the first hours of soaking. [ABSTRACT FROM AUTHOR]

Mesoporous bioactive glass nanoparticles (MBG) are multifunctional building blocks for tissue regeneration and nanomedicine applications. Incorporation of biologically active ions can endow MBG with additional functionalities toward promoted therapeutic effects. Here, boron is incorporated into MBG by using a sol–gel approach. The concentration of boron incorporated is controllable by tuning the amount of boron precursor. Two types of boron‐doped MBG, namely 10B‐ and 15B‐MBG (5.8 and 6.5 mol% of B2O3, respectively) are synthesized. Boron incorporation does not significantly influence the particle morphology. All synthesized particles exhibit a sphere‐like shape with a size ranging from 100 to 300 nm. 10B‐ and 15B‐MBG show large specific surface area (346 and 320 m² g−1, respectively) and pore volume. Both boron‐doped MBG exhibit remarkable in vitro bioactivity and noncytotoxicity. Boron incorporation is shown to reduce the inflammatory response linked to macrophages as indicated by downregulated expression of pro‐inflammatory genes. However, boron incorporation delays the osteogenic differentiation in osteoblasts as indicated by the downregulated expression of pro‐osteogenic genes. The results demonstrate the promising potential of using boron‐doped MBG to modulate inflammatory response for bone regeneration under inflammatory conditions, as shown in this study for the first time. [ABSTRACT FROM AUTHOR]

The objectives of this study are to evaluate long‐term wettability of novel surface‐engineered, clinically available dental implants, featuring a surface nanolayer of covalently linked hyaluronan, and to confirm the relationships between wetting properties and surface nanostructure and microstructure. Wettability measurements were performed on clinically available hyaluronan‐coated Grade 4 titanium implants, packaged and sterile, that is, in the "on the shelf" condition, after 1 year from production. Wetting properties were measured by the Wilhelmy plate method. Analysis of the surface structure and chemistry was perfomed by X‐ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy‐dispersive X‐ray (EDX) analysis, atomic force microscopy (AFM), and ζ‐potential measurement, either on implants or disks or plates subjected to the same surface‐engineering process. Results show that hydrophilicity and ensuing capillary rise of the hyaluronan‐coated implant surface is unaffected by aging and dry storage. Chemical analysis of the implant surface by XPS and evaluation of the ζ potential indicate that hyaluronan chemistry and not that of titanium dictates interfacial properties. Comparison between XPS versus EDX and SEM versus AFM data confirm that the thickness of the hyaluronan surface layer is within the nanometer range. Data show that nanoengineering of the implant surface by linking of the hydrophilic hyaluronan molecule endows tested titanium implants by permanent wettability, without need of wet storage as presently performed to keep long‐term hydrophilic implant surfaces. From an analytical point of view, the introduction in routine clinical practice of nanoengineered implant surfaces requires upgrading of analytical methods to the nanoscale. [ABSTRACT FROM AUTHOR]

Replacement of bone loss or reconstruction of bone defect is still a clinical challenge. Synergoss® is a recently developed synthetic bone filler that exploits biomolecular surface engineering to deliver directly to the filler-implant interface the signaling properties of type I collagen. In this article, we compared Synergoss ® bone filler with the most used materials present on the market derived from animal source (Bio-Oss®, Gen-Os®) or synthetic source (BoneCeramic®). All tested bone fillers were analyzed by ATR-IR, providing information concerning the chemical composition and the main functional groups. Surface zeta potential analysis shows a positive surface charge for Synergoss®, confirming that the material exposes a collagen nanolayer to the surrounding environment, unlike typical synthetic and bone-based fillers. The chemical composition of the first few nanometers of the surface of tested bone fillers was evaluated by XPS, and Synergoss ® shows a significant amount of nitrogen (9.8 at%), which is not detected in any of the remaining materials. Morphological structure of Synergoss® (analyzed by SEM) shows a uniformly distributed micro- and macroporosity, which plays an essential role in influencing cell adhesion and blood vessel infiltration, nutrient transportation, and clot formation to stimulate the overall healing process. [ABSTRACT FROM AUTHOR]

Oral diseases and periodontitis in particular are a major health burden worldwide, because of their association with various systemic diseases and with conditions such as peri-implantitis. Attempts have been made over the years to reverse bone loss due to the host disproportionate inflammatory response and to prevent failure of dental implants. To this end, the use of biomaterials functionalized with molecules characterized by anti-inflammatory and antioxidant properties could represent a new frontier for regenerating functional periodontal tissues. In this study, a new ceramic granulated biomaterial, named Synergoss Red (SR), functionalized with a polyphenolic mixture extracted from pomace of the Croatina grape variety, is introduced. Following a preliminary in-depth characterization of the extract by HPLC analysis and of the biomaterial surface and composition, we performed evaluations of cytocompatibility and a biological response through in vitro assays. The anti-inflammatory and antioxidant properties of the identified phenolic molecules contained in SR were shown to downregulate inflammation in macrophages, to stimulate in osteoblast-like cells the expression of genes involved in deposition of the early bone matrix, and to mitigate bone remodeling by decreasing the RANKL/OPG ratio. Thanks to its cytocompatibility and assorted beneficial effects on bone regeneration, SR could be considered an innovative regenerative approach in periodontal therapy. [ABSTRACT FROM AUTHOR]

To achieve optimal performances, guided bone regeneration membranes should have several properties, in particular, proper stiffness and tear resistance for space maintenance, appropriate resorption time, and non-cytotoxic effect. In this work, polyphenol-rich pomace extract (PRPE), from a selected grape variety (Nebbiolo), rich in proanthocyanidins and flavonols (e.g., quercetin), was used as a rich source of polyphenols, natural collagen crosslinkers, to improve the physical properties of the porcine pericardium membrane. The incorporation of polyphenols in the collagen network of the membrane was clearly identified by infra-red spectroscopy through the presence of a specific peak between 1360–1380 cm−1. Polyphenols incorporated into the pericardium membrane bind to collagen with high affinity and reduce enzymatic degradation by 20% compared to the native pericardium. The release study shows a release of active molecules from the membrane, suggesting a possible use in patients affected by periodontitis, considering the role of polyphenols in the control of this pathology. Mechanical stiffness is increased making the membrane easier to handle. Young's modulus of pericardium treated with PRPE was three-fold higher than the one measured on native pericardium. Tear and suture retention strength measurement suggest favorable properties in the light of clinical practice requirements. [ABSTRACT FROM AUTHOR]

Periodontal diseases involve injuries to the supporting structures of the tooth and, if left untreated, can lead to the loss of the tooth. Regenerative periodontal therapies aim, ideally, at healing all the damaged periodontal tissues and represent a significant clinical and societal challenge for the current ageing population. This review provides a picture of the currently-used biomaterials for periodontal regeneration, including natural and synthetic polymers, bioceramics (e.g., calcium phosphates and bioactive glasses), and composites. Bioactive materials aim at promoting the regeneration of new healthy tissue. Polymers are often used as barrier materials in guided tissue regeneration strategies and are suitable both to exclude epithelial down-growth and to allow periodontal ligament and alveolar bone cells to repopulate the defect. The problems related to the barrier postoperative collapse can be solved by using a combination of polymeric membranes and grafting materials. Advantages and drawbacks associated with the incorporation of growth factors and nanomaterials in periodontal scaffolds are also discussed, along with the development of multifunctional and multilayer implants. Tissue-engineering strategies based on functionally-graded scaffolds are expected to play an ever-increasing role in the management of periodontal defects. [ABSTRACT FROM AUTHOR]

Biochemical modification of titanium surfaces (BMTiS) entails immobilization of biomolecules to implant surfaces in order to induce specific host responses. This crossover randomized clinical trial assesses clinical success and marginal bone resorption of dental implants bearing a surface molecular layer of covalently-linked hyaluronan in comparison with control implants up to 36 months after loading. Patients requiring bilateral implant rehabilitation received hyaluronan covered implants in one side of the mouth and traditional implants in the other side. Two months after the first surgery, a second surgery was undergone to uncover the screw and to place a healing abutment. After two weeks, the operator proceeded with prosthetic procedures. Implants were evaluated by periapical radiographs and the crestal bone level was recorded at mesial and distal sites—at baseline and up to 36 months. One hundred and six implants were positioned, 52 HY-coated, and 48 controls were followed up. No differences were observed in terms of insertion and stability, wound healing, implant success, and crestal bone resorption at any time considered. All interventions had an optimal healing, and no adverse events were recorded. This trial shows, for the first time, a successful use in humans of biochemical-modified implants in routine clinical practice and in healthy patients and tissues with satisfactory outcomes. [ABSTRACT FROM AUTHOR]

Background: The process of osseointegration of dental implants is characterized by healing phenomena at the level of the interface between the surface and the bone. Implant surface modification has been introduced in order to increase the level of osseointegration. The purpose of this study is to evaluate the influence of biofunctional coatings for dental implants and the bone healing response in a rabbit model. The implant surface coated with collagen type I was analyzed through X-ray Photoelectron Spectroscopy (XPS), Atomic Force Microscopy (AFM), micro-CT and histologically. Methods: The sandblasted and double acid etched surface coated with collagen type I, and uncoated sandblasted and double acid etched surface were evaluated by X-ray Photoelectron Spectroscopy (XPS) and Atomic Force Microscopy (AFM) analysis in order evaluate the different morphology. In vivo, a total of 36 implants were positioned in rabbit articular femoral knee-joint, 18 fixtures for each surface. Micro-CT scans, histological and histomorphometrical analysis were conducted at 15, 30 and 60 days. Results: A histological statistical differences were evident at 15, 30 and 60 days (p < 0.001). Both implant surfaces showed a close interaction with newly formed bone. Mature bone appeared in close contact with the surface of the fixture. The AFM outcome showed a similar roughness for both surfaces. Conclusion: However, the final results showed that a coating of collagen type I on the implant surface represents a promising procedure able to improve osseointegration, especially in regions with a low bone quality. [ABSTRACT FROM AUTHOR]

Over the recent years, mesoporous bioactive glasses (MBGs) gained interest as bone regeneration systems, due to their excellent bioactivity and ability to release therapeutic molecules. In order to improve the bone regeneration ability of MBGs, the incorporation of Sr2+ ions, due to its recognized pro-osteogenenic potential, represents a very promising strategy. In this study, MBGs based on the SiO2–CaO system and containing different percentages (2 and 4 mol %) of strontium were prepared by two synthesis methods, in the form of microspheres and nanoparticles. Sr-containing MBGs were characterized by FE-SEM, XRD and N2 adsorption/desorption analysis. The in vitro bioactivity in SBF resulted excellent. The assessment of fibroblast cell (line L929) viability showed that Sr-containing MBGs were biocompatible both in form of micro- and nanoparticles. The osteogenic response of osteoblast-like SAOS-2 cells was investigated by analysing the expression of GAPDH, COL1a1, RANKL, SPARC, OPG and ALPL genes, as cell differentiation markers. The results indicate that the incorporation of Sr into MBG is beneficial for bone regeneration as promotes a pro-osteogenic effect, paving the way to the design of advanced devices enabled by these nanocarriers also in combination with drug release, for the treatment of bone pathologies, particularly in patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Introduction: Silver decorated mesoporous carbons are interesting systems that may offer effective solutions for advanced wound care products by combining the well-known anti-microbial activity of silver nanoparticles with the versatile properties of ordered mesoporous carbons. Silver is being used as a topical antimicrobial agent, especially in wound repair. However, while silver shows bactericidal properties, it is also cytotoxic at high concentrations. Therefore, the incorporation of silver into ordered mesoporous carbons allows to exploit both silver's biological effects and mesoporous carbons' biocompatibility and versatility with the purpose of conceiving silver-doped materials in light of the growing health concern in wound care., Methods: The wound healing potential of an ordered mesoporous carbon also doped with two different loadings of silver nanoparticles (2 wt% and 10 wt%), was investigated through a biological assessment study based on different assays (cell viability, inflammation, antibacterial tests, macrophage-conditioned fibroblast and human keratinocyte cell cultures)., Results: The results show silver-doped ordered mesoporous carbons to positively condition cell viability, with a cell viability percentage >70% even for 10 wt% Ag, to modulate the expression of inflammatory cytokines and of genes involved in tissue repair (KRT6a, VEGFA, IVN) and remodeling (MMP9, TIMP3) in different cell systems. Furthermore, along with the biocompatibility and the bioactivity, the silver-doped ordered mesoporous carbons still retain an antibacterial effect, as shown by a maximum of 13.1% of inhibited area in the Halo test. The obtained results clearly showed that the silver-doped ordered mesoporous carbons exhibit both good biocompatibility and antibacterial effect with enhanced re-epithelialization, angiogenesis promotion and tissue regeneration., Discussion: These findings suggest that the exceptional properties of silver-doped ordered mesoporous carbons could be exploited in the treatment of acute and chronic wounds and that such carbon materials could be potential candidates for use in medical devices for wound healing purposes, in particular, the 10 wt% loading, as the results showed to be the most effective., Competing Interests: There are no potential conflicts of interest to declare., (© 2019 Torre et al.)

Carbon nanotube (CNT)-based nanocomposites often possess properties such as high stiffness, electrical conductivity, and thermal stability and have been studied for various biomedical and biotechnological applications. However, the current design approaches utilize CNTs as physical filler, and thus, the true potential of CNT-based nanocomposites has not been achieved. Here, we introduce a general approach of fabricating stiff, elastomeric nanocomposites from poly(glycerol sebacate) (PGS) and CNTs. The covalent crosslinking between the nanotubes and polymer chains resulted in novel property combinations that are not observed in conventional nanocomposites. The addition of 1% CNTs resulted a five-fold increase in the tensile modulus and a six-fold increase in compression modulus compared with PGS alone, which is far superior to the previously reported studies for CNT-based nanocomposites. Despite significant increase in mechanical stiffness, the elasticity of the network was not compromised and the resulting nanocomposites showed more than 94% recovery. This study demonstrates that the chemical conjugation of CNTs to a PGS backbone results in stiff and elastomeric nanocomposites. Additionally, in vitro studies using human mesenchymal stem cells (hMSCs) indicated that the incorporation of CNTs to PGS network significantly enhanced the differentiation potential of the seeded hMSCs rendering them potentially suitable for applications ranging from scaffolding in musculoskeletal tissue engineering to biosensors in biomedical devices.

Musculoskeletal tissue engineering aims at repairing and regenerating damaged tissues using biological tissue substitutes. One approach to achieve this aim is to develop osteoconductive scaffolds that facilitate the formation of functional bone tissue. We have fabricated nanoclay-enriched electrospun poly(ɛ-caprolactone) (PCL) scaffolds for osteogenic differentiation of human mesenchymal stem cells (hMSCs). A range of electrospun scaffolds is fabricated by varying the nanoclay concentrations within the PCL scaffolds. The addition of nanoclay decreases fiber diameter and increases surface roughness of electrospun fibers. The enrichment of PCL scaffold with nanoclay promotes in vitro biomineralization when subjected to simulated body fluid (SBF), indicating bioactive characteristics of the hybrid scaffolds. The degradation rate of PCL increases due to the addition of nanoclay. In addition, a significant increase in crystallization temperature of PCL is also observed due to enhanced surface interactions between PCL and nanoclay. The effect of nanoclay on the mechanical properties of electrospun fibers is also evaluated. The feasibility of using nanoclay-enriched PCL scaffolds for tissue engineering applications is investigated in vitro using hMSCs. The nanoclay-enriched electrospun PCL scaffolds support hMSCs adhesion and proliferation. The addition of nanoclay significantly enhances osteogenic differentiation of hMSCs on the electrospun scaffolds as evident by an increase in alkaline phosphates activity of hMSCs and higher deposition of mineralized extracellular matrix compared to PCL scaffolds. Given its unique bioactive characteristics, nanoclay-enriched PCL fibrous scaffold may be used for musculoskeletal tissue engineering.

Hyperbranched polyesters (HPE) have a high efficiency to encapsulate bioactive agents, including drugs, genes, and proteins, due to their globe-like nanostructure. However, the use of these highly branched polymeric systems for tissue engineering applications has not been broadly investigated. Here, we report synthesis and characterization of photocrosslinkable HPE hydrogels with sustained drug release characteristics for cellular therapies. These HPE can encapsulate hydrophobic drug molecules within the HPE cavities due to the presence of a hydrophobic inner structure that is otherwise difficult to achieve in conventional hydrogels. The functionalization of HPE with photocrosslinkable acrylate moieties renders the formation of hydrogels with a highly porous interconnected structure and mechanically tough network. The compressive modulus of HPE hydrogels was tunable by changing the crosslinking density. The feasibility of using these HPE networks for cellular therapies was investigated by evaluating cell adhesion, spreading, and proliferation on hydrogel surface. Highly crosslinked and mechanically stiff HPE hydrogels have higher cell adhesion, spreading, and proliferation compared to soft and complaint HPE hydrogels. Overall, we showed that hydrogels made from HPE could be used for biomedical applications that require spatial control of cell adhesion and controlled release of hydrophobic clues.