In Vivo Osteogenic and Angiogenic Properties of a 3D-Printed Isosorbide-Based Gyroid Scaffold Manufactured via Digital Light Processing.

INTRODUCTION: Osteogenic and angiogenic properties of synthetic bone grafts play a crucial role in the restoration of bone defects. Angiogenesis is recognised for its support in bone regeneration, particularly in larger defects. The objective of this study is to evaluate the new bone formation and neovascularisation of a 3D-printed isosorbide-based novel CSMA-2 polymer in biomimetic gyroid structures. METHODS: The gyroid scaffolds were fabricated by 3D printing CSMA-2 polymers with different hydroxyapatite (HA) filler concentrations using the digital light processing (DLP) method. A small animal subcutaneous model and a rat calvaria critical-size defect model were performed to analyse tissue compatibility, angiogenesis, and new bone formation. RESULTS: The in vivo results showed good biocompatibility of the 3D-printed gyroid scaffolds with no visible prolonged inflammatory reaction. Blood vessels were found to infiltrate the pores from day 7 of the implantation. New bone formation was confirmed with positive MT staining and BMP-2 expression, particularly on scaffolds with 10% HA. Bone volume was significantly higher in the CSMA-2 10HA group compared to the sham control group. DISCUSSION AND CONCLUSIONS: The results of the subcutaneous model demonstrated a favourable tissue response, including angiogenesis and fibrous tissue, indicative of the early wound healing process. The results from the critical-size defect model showcased new bone formation, as confirmed by micro-CT imaging and immunohistochemistry. The combination of CSMA-2 as the 3D printing material and the gyroid as the 3D structure was found to support essential events in bone healing, specifically angiogenesis and osteogenesis.

Digital Light Processing 3D Printing of Gyroid Scaffold with Isosorbide-Based Photopolymer for Bone Tissue Engineering.

As one of the most transplanted tissues of the human body, bone has varying architectures, depending on its anatomical location. Therefore, bone defects ideally require bone substitutes with a similar structure and adequate strength comparable to native bones. Light-based three-dimensional (3D) printing methods allow the fabrication of biomimetic scaffolds with high resolution and mechanical properties that exceed the result of commonly used extrusion-based printing. Digital light processing (DLP) is known for its faster and more accurate printing than other 3D printing approaches. However, the development of biocompatible resins for light-based 3D printing is not as rapid as that of bio-inks for extrusion-based printing. In this study, we developed CSMA-2, a photopolymer based on Isosorbide, a renewable sugar derivative monomer. The CSMA-2 showed suitable rheological properties for DLP printing. Gyroid scaffolds with high resolution were successfully printed. The 3D-printed scaffolds also had a compressive modulus within the range of a human cancellous bone modulus. Human adipose-derived stem cells remained viable for up to 21 days of incubation on the scaffolds. A calcium deposition from the cells was also found on the scaffolds. The stem cells expressed osteogenic markers such as RUNX2, OCN, and OPN. These results indicated that the scaffolds supported the osteogenic differentiation of the progenitor cells. In summary, CSMA-2 is a promising material for 3D printing techniques with high resolution that allow the fabrication of complex biomimetic scaffolds for bone regeneration.

Inclusion of calcium phosphate does not further improve in vitro and in vivo osteogenesis in a novel, highly biocompatible, mechanically stable and 3D printable polymer.

At a time of unpredictable challenges for health, one trend is certain: there is an exceedingly high demand for functional implants, particularly bone grafts. This has encouraged the emergence of bone tissue engineering substitutes as an alternative method to conventional bone grafts. However, the current approaches in the field face several limitations that have prevented the ultimate translation into clinical settings. As a result, many attempts have been made to fabricate synthetic bone implants that can offer suitable biological and mechanical properties.Light curable methacrylate-based polymers have ideal properties for bone repair. These materials are also suitable for 3D printing which can be applicable for restoration of both function and aesthetics. The main objective of this research was to investigate the role of calcium phosphate (CaP) incorporation in a mechanically stable, biologically functional and 3D printable polymer for the reconstruction of complex craniofacial defects. The experimental work initially involved the synthesis of (((((((((((3R,3aR,6S,6aR)- hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1- 48 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(3,3,5-trimethylcyclohexane-5,1- 49 diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane-2,1-diyl) bis(2-methylacrylate) referred to as CSMA and fabrication of composite discs via a Digital Light Printing (DLP) method. The flow behaviour of the polymer as a function of CaP addition, surface remineralisation potential, in vitro cell culture, using MC3T3 and Adipose-Derived Mesenchymal Stem Cells (ADSCs) and ex ovo angiogenic response was assessed. Finally, in vivo studies were carried out to investigate neo-bone formation at 4- and 8-weeks post-implantation. Quantitative micro-CT and histological evaluation did not show a higher rate of bone formation in CaP filled CSMA composites compared to CSMA itself. Therefore, such polymeric systems hold promising features by allowing more flexibility in designing a 3D printed scaffold targeted at the reconstruction of maxillofacial defects.

Hyperelastic, shape-memorable, and ultra-cell-adhesive degradable polycaprolactone-polyurethane copolymer for tissue regeneration.

Novel polycaprolactone-based polyurethane (PCL-PU) copolymers with hyperelasticity, shape-memory, and ultra-cell-adhesion properties are reported as clinically applicable tissue-regenerative biomaterials. New isosorbide derivatives (propoxylated or ethoxylated ones) were developed to improve mechanical properties by enhanced reactivity in copolymer synthesis compared to the original isosorbide. Optimized PCL-PU with propoxylated isosorbide exhibited notable mechanical performance (50 MPa tensile strength and 1150% elongation with hyperelasticity under cyclic load). The shape-memory effect was also revealed in different forms (film, thread, and 3D scaffold) with 40%-80% recovery in tension or compression mode after plastic deformation. The ultra-cell-adhesive property was proven in various cell types which were reasoned to involve the heat shock protein-mediated integrin (α5 and αV) activation, as analyzed by RNA sequencing and inhibition tests. After the tissue regenerative potential (muscle and bone) was confirmed by the myogenic and osteogenic responses in vitro, biodegradability, compatible in vivo tissue response, and healing capacity were investigated with in vivo shape-memorable behavior. The currently exploited PCL-PU, with its multifunctional (hyperelastic, shape-memorable, ultra-cell-adhesive, and degradable) nature and biocompatibility, is considered a potential tissue-regenerative biomaterial, especially for minimally invasive surgery that requires small incisions to approach large defects with excellent regeneration capacity.

Comparative study of photoinitiators for the synthesis and 3D printing of a light-curable, degradable polymer for custom-fit hard tissue implants.

Three-dimensional (3D) printing enhances the production of on-demand fabrication of patient-specific devices, as well as anatomically fitting implants with high complexity in a cost-effective manner. Additive systems that employ vat photopolymerisation such as stereolithography (SLA) and digital light projection are used widely in the field of biomedical science and engineering. However, additive manufacturing methods can be limited by the types of materials that can be used. In this study, we present an isosorbide-based formulation for a polymer resin yielding a range of elastic moduli between 1.7 and 3 GN mm-2 dependent on the photoinitiator system used as well as the amount of calcium phosphate filler added. The monomer was prepared and enhanced for 3D-printing using an SLA technique that delivered stable and optimized 3D-printed models. The resin discussed could potentially be used following major surgery for the correction of congenital defects, the removal of oral tumours and the reconstruction of the head and neck region. The surgeon is usually limited with devices available to restore both function and appearance and with the ever-increasing demand for low-priced and efficient facial implants, there is an urgent need to advance new manufacturing approaches and implants with a higher osseointegration performance.

Nano-graphene oxide/polyurethane nanofibers: mechanically flexible and myogenic stimulating matrix for skeletal tissue engineering.

For skeletal muscle engineering, scaffolds that can stimulate myogenic differentiation of cells while possessing suitable mechanical properties (e.g. flexibility) are required. In particular, the elastic property of scaffolds is of importance which helps to resist and support the dynamic conditions of muscle tissue environment. Here, we developed highly flexible nanocomposite nanofibrous scaffolds made of polycarbonate diol and isosorbide-based polyurethane and hydrophilic nano-graphene oxide added at concentrations up to 8%. The nano-graphene oxide incorporation increased the hydrophilicity, elasticity, and stress relaxation capacity of the polyurethane-derived nanofibrous scaffolds. When cultured with C2C12 cells, the polyurethane-nano-graphene oxide nanofibers enhanced the initial adhesion and spreading of cells and further the proliferation. Furthermore, the polyurethane-nano-graphene oxide scaffolds significantly up-regulated the myogenic mRNA levels and myosin heavy chain expression. Of note, the cells on the flexible polyurethane-nano-graphene oxide nanofibrous scaffolds could be mechanically stretched to experience dynamic tensional force. Under the dynamic force condition, the cells expressed significantly higher myogenic differentiation markers at both gene and protein levels and exhibited more aligned myotubular formation. The currently developed polyurethane-nano-graphene oxide nanofibrous scaffolds, due to their nanofibrous morphology and high mechanical flexibility, along with the stimulating capacity for myogenic differentiation, are considered to be a potential matrix for future skeletal muscle engineering.

Synthesis, Characterization, and 3D Printing of an Isosorbide-Based, Light-Curable, Degradable Polymer for Potential Application in Maxillofacial Reconstruction.

Although emergence of bone tissue engineering techniques has revolutionized the field of maxillofacial reconstruction, the successful translation of such products, especially concerning larger sized defects, still remains a significant challenge. Light-curable methacrylate-based polymers have ideal properties for bone repair. These materials are also suitable for 3D printing which can be applicable for restoration of both function and aesthetics. The main objective of this research was to synthesize a mechanically stable and biologically functional polymer for reconstruction of complex craniofacial defects. The experimental work initially involved synthesis of (((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1-diyl)bis((4-methyl-3-oxopent-4-en-1-yl)carbamate), CSMA-1, and ((((((((((((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(methylene))bis(3,3,5-trimethylcyclohexane-5,1-diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane-2,1-diyl)bis(2-methylacrylate), CSMA-2; nuclear magnetic resonance analysis confirmed formation of the monomers, and composite samples were fabricated respectively by exposing 11 mm diameter discs to blue light. Modulus of elasticity was determined using a biaxial flexural test and the values were found to be between 1 and 3 GPa in CSMA-1, CSMA-2, and their composites. In vitro cell culture, using human bone marrow-derived mesenchymal stem cells, confirmed nontoxicity of the samples and finally 3D printing allowed direct photo-polymerization and setting of the bio ink into a 3D construct.

Roll-to-roll graphene oxide radon barrier membranes.

Graphene oxide as a radon barrier in living environments was introduced by intercalating the polymer resin-coated layer inside a multilayer membrane with an area of 1 × 10 m and a thickness of 2.5 mm, prepared by the roll-to-roll method. A 5 µm-thick graphene oxide polymer resin (GOPR) layer was coated on polyethylene terephthalate (PET) film (100 µm) between the two styrene-butadiene-styrene (SBS)-modified bitumen asphalt layers fitted for construction sites. The inserted graphene oxide materials were characterized by means of infrared, Raman, and X-ray photoelectron spectroscopy (XPS). Dispersion-corrected density functional theory (DFT) calculations suggested weaker binding energies on the oxide surfaces and higher penetration energy barriers of graphene nanopores for radon (222Rn) than in the cases of the atmospheric gas molecules Ar, H2O, CO2, H2, O2, and N2. Theoretical calculations of the graphene nanopores supported the higher barrier energies of 222Rn than most ambient gases. The roll-to-roll prepared graphene materials exhibited good barrier properties for 222Rn as well as for the ambient gases. The purpose of our experimental and theoretical study is to provide a better understanding of using graphene-based materials to reduce the risk of carcinogenic radon gas in construction sites and residential buildings for practical applications.

Development of Bis-GMA-free biopolymer to avoid estrogenicity.

OBJECTIVE: Although bisphenol A-glycidyl methacrylate (Bis-GMA)-based dental materials are widely used in dentistry, Estrogenicity from released bisphenol A remains a concern due to possibility of adversely affecting the growth of children and homeostasis of adults. Here, a new family of isosorbide-derived biomonomers were synthesized and experimentally utilized as a matrix of dental sealants to provide physico-mechanical and biological properties comparable to those of a conventional Bis-GMA-based material but without the the potential estrogenicity. METHODS: After synthesis of isosorbide-derived biomonomers (ISDB) by light polymerization, an experimental dental sealant with different silica filler concentrations (0-15wt%) was characterized and compared to a commercially available Bis-GMA-based sealant. Cytotoxicity and estrogenicity assays were conducted with human oral keratinocytes and estrogen-sensitive MCF-7 cells, respectively. RESULTS: ISDB-based dental sealants exhibited typical initially smooth surfaces with depth of cure, Vickers hardness, compressive strength/modulus, water resorption/solubility, and flowability comparable to those of the commercial sealant and met the ISO standard for dental sealants and polymer-based restorative materials. Indirect cytotoxicity tests using an extract showed comparable viability among experimental ISDB-based materials and a commercial Bis-GMA-incorporated control. DNA synthesis in MCF-7 cells (a marker of estrogenicity) and the release of bisphenol A under enzymatic incubation were not detected in ISDB-based materials. SIGNIFICANCE: In conclusion, the comparable physico-mechanical properties of ISDB-based materials with their cytocompatibility and lack of estrogenicity suggest the potential usefulness of ISDBs as a newly developed and safe biomaterial.

Sugammadex affects emergence agitation in children undergoing strabismus surgery.

Objective Emergence agitation (EA) has a multifactorial origin, and the effect of sugammadex on EA has not been established. We investigated the effect of sugammadex on EA incidence and severity. Methods We performed a retrospective study of children aged 1 to 13 years who underwent strabismus surgery. Patients received sugammadex or conventional neuromuscular reversal agents. The primary outcome variables were EA incidence and severity. Secondary outcome variables were postoperative fentanyl use, postoperative nausea and vomiting, time from reversal agent administration to extubation, time from the end of surgery to arrival in the post-anesthesia care unit (PACU) and time spent in the PACU. We used propensity score matching to eliminate baseline imbalances. Results Age, sex, use of desflurane, and intraoperative fentanyl were significant predictors of agitation severity using a multivariable analysis. Sugammadex did not significantly affect EA in logistic regression and multiple regression analyses. In the propensity-matched analysis, patients in the sugammadex group showed rapid recovery, but there was no difference in the EA incidence or severity. Conclusion Sugammadex did not affect EA incidence or severity compared with conventional cholinesterase inhibitors, although it showed a favorable recovery profile in children undergoing strabismus surgery.

Biodegradable shape-memory polymers using polycaprolactone and isosorbide based polyurethane blends.

Thermally responsive shape-memory polymers have received widespread attention in the biomedical field. In this study, biocompatible and biodegradable polyurethane (PU) and polycaprolactone (PCL) were blended to obtain shape-memory properties. Highly crystalline PCL was used as a hard segment, and PU synthesized from isosorbide, which is non-toxic and chemically and thermally stable, was used as a soft segment. The obtained PU/PCL blends containing the 30%, 50%, and 70% PU by weight were investigated for their thermal properties, mechanical properties, and shape-memory behavior. The 30%PU/PCL polymer has the best shape-memory characteristics and can be knotted by itself in the hot water bath, indicating that it can be applied in smart suture applications. The degradation test performed at 37 °C in phosphate buffered solution showed a mass loss of 2-4% for the obtained PU/PCL blends after 6 weeks. Finally, MC3T3-E1 cells cultured on PU/PCL blends showed high biocompatibility due to high adhesion and proliferation.

New spiro[benzotetraphene-fluorene] derivatives: synthesis and application in sky-blue fluorescent host materials.

Blue light-emitting spiro[benzotetraphene-fluorene] (SBTF)-based host materials, 3-(1-naphthyl)-10-naphthylspiro[benzo[ij]tetraphene-7,9'-fluorene] (1), 3-(2-naphthyl)-10-naphthylspiro[benzo[ij]tetraphene-7,9'-fluorene] (2), and 3-[2-(6-phenyl)naphthyl]-10-naphthylspiro[benzo[ij]tetraphene-7,9'-fluorene] (3) were designed and prepared via multi-step Suzuki coupling reactions. Introducing various aromatic groups into SBTF core lead to a reduction in band gap and a determination of the color purity and luminescence efficiency. Typical sky-blue fluorescent organic light emitting diodes with the configuration of ITO/N,N'-di(1-naphthyl)-N,N'-bis[(4-diphenylamino)phenyl]-biphenyl-4,4'-diamie (60 nm)/N,N,N',N'-tetra(1-biphenyl)-biphenyl-4,4'-diamine (30 nm)/host: dopant (30 nm, 5%)/LG201 (electron transporting layer, 20 nm)/LiF/Al were developed using SBTF derivatives as a host material and p-bis(p-N,N-diphenyl-aminostyryl)benzene (DSA-Ph) as a sky-blue dopant material. A device obtained from three materials doped with DSA-Ph showed color purity of 0.148 and 0.239, a luminance efficiency of 7.91 cd/A, and an external quantum efficiency >4.75% at 5 V.