Development of a clot-adhesive coating to improve the performance of thrombectomy devices.

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.

Engineering Interfacial Environment of Epigallocatechin Gallate Coated Titanium for Next-Generation Bioactive Dental Implant Components.

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.

Mesoporous Bioactive Glasses Incorporated into an Injectable Thermosensitive Hydrogel for Sustained Co-Release of Sr2+ Ions and N-Acetylcysteine.

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.

Functionalization with a Polyphenol-Rich Pomace Extract Empowers a Ceramic Bone Filler with In Vitro Antioxidant, Anti-Inflammatory, and Pro-Osteogenic Properties.

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.

Polyphenols from grape pomace induce osteogenic differentiation in mesenchymal stem cells.

Polyphenols are increasingly investigated for the treatment of periodontitis and research on their use in dental biomaterials is currently being conducted. Grape pomace extracts are a rich source of polyphenols. In the present study, the polyphenols of two different types of grape pomace were characterized and identified by high­performance liquid chromatography­diode array detector, and the effect of polyphenol­rich grape pomace extracts on mesenchymal stem cell (MSC) osteogenic differentiation was investigated. Solid­liquid extraction was used to recover polyphenols from red and white grape pomace. The two extracts have been characterized through the phenolic content and antioxidant power. Human MSCs (hMSCs) from the bone marrow were cultured both with and without given amounts (10 or 20 µg/ml) of the obtained pomace extracts. Their effects on cell differentiation were evaluated by reverse transcription­quantitative polymerase chain reaction, compared with relevant controls. Results showed that both pomace extracts, albeit different in phenolic composition and concentration, induced multiple effects on hMSC gene expression, such as a decreased receptor activator of nuclear factor κ­Β ligand/osteoprotegerin ratio and an enhanced expression of genes involved in osteoblast differentiation, thus suggesting a shift of hMSCs towards osteoblast differentiation. The obtained results provided data in favor of the exploitation of polyphenol properties from grape pomace extracts as complementary active molecules for dental materials and devices for bone regeneration in periodontal defects.

Antioxidant mesoporous Ce-doped bioactive glass nanoparticles with anti-inflammatory and pro-osteogenic activities.

Mesoporous bioactive glass nanoparticles (MBGNs) are emerging biomaterials for bone repair/regeneration, considering their favorable pro-osteogenic and proangiogenic activities. To further improve their therapeutic effects, the endowment of MBGNs with additional antioxidant properties is of particular interest to target oxidative stress related to bone remodeling and diseases. To this end, we developed antioxidant cerium-containing MBGNs (Ce-MBGNs) (particle size of 100-300 â€‹nm) by using a postimpregnation strategy to incorporate Ce, through which the shape, pore structure, and dispersity of the nanoparticles were preserved. The incorporated amount of Ce could be tailored by adjusting the concentration of the Ce precursor solution. When impregnated at a relatively low temperature (20 â€‹°C), Ce-MBGNs containing either 1.8 or 2.8 â€‹mol% of Ce were produced, while the formation of by-product cerium oxide nanoparticles (nanoceria) could be avoided. In both developed Ce-MBGNs, the concentration of Ce4+ was higher than that of Ce3+, while the relative molar percentage of Ce4+ was similar (∼74%) in both Ce-MBGNs. The obtained Ce-MBGNs were evidenced to be non-cytotoxic against fibroblasts at the concentration of 1 â€‹mg/mL. Moreover, the incorporation of Ce into MBGNs significantly reduced the expression of oxidative stress-related genes in macrophages (J774a.1). Particularly in the presence of pro-oxidation agents, Ce-MBGNs could downregulate the expression of oxidative stress-related genes in comparsion with the polystyrene plates (control). When cultured with Ce-MBGNs, the expression of proinflammatory-related genes in macrophages could also be downregulated in comparsion with MBGNs and the control. Ce-MBGNs also exhibited pro-osteogenic activities through suppressing pro-osteoclastogenic responses. The obtained results highlight the great potential of the developed Ce-MBGNs in a variety of biomedical applications, particularly in treating bone defects under inflammatory conditions, considering their antioxidant, anti-inflammatory, and pro-osteogenesis activities.

Improvement of the Physical Properties of Guided Bone Regeneration Membrane from Porcine Pericardium by Polyphenols-Rich Pomace Extract.

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.

Biomimetic Surfaces Coated with Covalently Immobilized Collagen Type I: An X-Ray Photoelectron Spectroscopy, Atomic Force Microscopy, Micro-CT and Histomorphometrical Study in Rabbits.

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.

Covalently-Linked Hyaluronan versus Acid Etched Titanium Dental Implants: A Crossover RCT in Humans.

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.

Biomaterials, Current Strategies, and Novel Nano-Technological Approaches for Periodontal Regeneration.

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.

Silver Decorated Mesoporous Carbons for the Treatment of Acute and Chronic Wounds, in a Tissue Regeneration Context.

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.

Permanent wettability of a novel, nanoengineered, clinically available, hyaluronan-coated dental implant.

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.

The Incorporation of Strontium to Improve Bone-Regeneration Ability of Mesoporous Bioactive Glasses.

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.

Engineered porous scaffolds for periprosthetic infection prevention.

Periprosthetic infection is a consequence of implant insertion procedures and strategies for its prevention involve either an increase in the rate of new bone formation or the release of antibiotics such as vancomycin. In this work we combined both strategies and developed a novel, multifunctional three-dimensional porous scaffold that was produced using hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP), coupled with a pectin (PEC)-chitosan (CHIT) polyelectrolyte (PEI), and loaded with vancomycin (VCA). By this approach, a controlled vancomycin release was achieved and serial bacterial dilution test demonstrated that, after 1week, the engineered construct still inhibits the bacterial growth. Degradation tests show an excellent behavior in a physiological and acidic environment (<10% of mass loss). Furthermore, the PEI coating shows an anti-inflammatory response, and good cell proliferation and migration were demonstrated in vitro using osteoblast SAOS-2 cell line. This new engineered construct exhibits excellent properties both as an antibacterial material and as a stimulator of bone formation, which makes it a good candidate to contrast periprosthetic infection.

Novel bioceramic-reinforced hydrogel for alveolar bone regeneration.

UNLABELLED: The osseointegration of dental implants and their consequent long-term success is guaranteed by the presence, in the extraction site, of healthy and sufficient alveolar bone. Bone deficiencies may be the result of extraction traumas, periodontal disease and infection. In these cases, placement of titanium implants is contraindicated until a vertical bone augmentation is obtained. This goal is achieved using bone graft materials, which should simulate extracellular matrix (ECM), in order to promote osteoblast proliferation and fill the void, maintaining the space without collapsing until the new bone is formed. In this work, we design, develop and characterize a novel, moldable chitosan-pectin hydrogel reinforced by biphasic calcium phosphate particles with size in the range of 100-300µm. The polysaccharide nature of the hydrogel mimics the ECM of natural bone, and the ceramic particles promote high osteoblast proliferation, assessed by Scanning Electron Microscopy analysis. Swelling properties allow significant adsorption of water solution (up to 200% of solution content) so that the bone defect space can be filled by the material in an in vivo scenario. The incorporation of ceramic particles makes the material stable at different pH and increases the compressive elastic modulus, toughness and ultimate tensile strength. Furthermore, cell studies with SAOS-2 human osteoblastic cell line show high cell proliferation and adhesion already after 72h, and the presence of ceramic particles increases the expression of alkaline phosphatase activity after 1week. These results suggest a great potential of the developed moldable biomaterials for the regeneration of the alveolar bone. STATEMENT OF SIGNIFICANCE: The positive fate of a surgical procedure involving the insertion of a titanium screw still depends on the quality and quantity of alveolar bone which is present in the extraction site. Available materials are basically hard scaffold materials with un-predictable behavior in different condition and difficult shaping properties. In this work we developed a novel pectin-chitosan hydrogel reinforced with ceramic particles. Polysaccharides simulate the extracellular matrix of natural bone and the extensive in vitro cells culture study allows to assess that the incorporation of the ceramic particles promote a pro-osteogenic response. Shape control, easy adaption of the extraction site, predictable behavior in different environment condition, swelling properties and an anti-inflammatory response are the significant characteristics of the developed biomaterial.

Elastomeric nanocomposite scaffolds made from poly (glycerol sebacate) chemically crosslinked with carbon nanotubes.

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.

Elastomeric nanocomposite scaffolds made from poly(glycerol sebacate) chemically crosslinked with carbon nanotubes.

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 fillers, and thus, the true potential of CNT-based nanocomposites has not been realized. Here, we introduce a general approach to 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 in 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 a 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 into the 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.

Nanoclay-enriched poly(ɛ-caprolactone) electrospun scaffolds for osteogenic differentiation of human mesenchymal stem cells.

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.

Highly elastomeric poly(glycerol sebacate)-co-poly(ethylene glycol) amphiphilic block copolymers.

Poly(glycerol sebacate) (PGS), a tough elastomer, has been proposed for tissue engineering applications due to its desired mechanical properties, biocompatibility and controlled degradation. Despite interesting physical and chemical properties, PGS shows limited water uptake capacity (∼2%), thus constraining its utility for soft tissue engineering. Therefore, a modification of PGS that would mimic the water uptake and water retention characteristics of natural extracellular matrix is beneficial for enhancing its utility for biomedical applications. Here, we report the synthesis and characterization of highly elastomeric poly(glycerol sebacate)-co-polyethylene glycol (PGS-co-PEG) block copolymers with controlled water uptake characteristics. By tailoring the water uptake property, it is possible to engineer scaffolds with customized degradation and mechanical properties. The addition of PEG results in almost 15-fold increase in water uptake capacity of PGS, and improves its mechanical stability under dynamic loading conditions. PGS-co-PEG polymers show elastomeric properties and can be subjected to serve deformation such as bending and stretching. The Young's modulus of PGS-co-PEG can be tuned from 13 kPa to 2.2 MPa by altering the amount of PEG within the copolymer network. Compared to PGS, more than six-fold increase in elongation was observed upon PEG incorporation. In addition, the rate of degradation increases with an increase in PEG concentration, indicating that degradation rate of PGS can be regulated. PGS-co-PEG polymers also support cell proliferation, and thus can be used for a range of tissue engineering applications.

Hyperbranched polyester hydrogels with controlled drug release and cell adhesion properties.

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.