Poly(acrylamide)-co-poly(hydroxyethyl)methacrylate-co-poly(cyclohexyl methacrylate) hydrogel platform for stability, storage and biocatalytic applications of urease.

In our present work, an explicit crosslinked thermo-responsive hydrogel platform has been developed, by using polyacrylamide (PAAm), poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(cyclohexyl methacrylate) (PCHMA), and then coupled with urease to yield bioconjugates (BCs). Synergic effect of these polymer units provides thermoresponsive nature, optimum crosslinking with desired swelling behaviour, and stability and improved catalytic to Urease in the resultant BCs. Synthesis of the terpolymer has been achieved by employing HEMA (monomer as well as crosslinker), instead of using the conventional crosslinkers, through free radical solution polymerization technique. Various grades of TRPUBs have been fabricated by varying HEMA and CHMA contents while keeping fixed amounts of AAm. Further, the structural analysis of BCs has been done by fourier transform infra-red spectroscopic study and their thermal stabilities have been studied by thermogravimetric analysis. Urea present in TRPUBs has beenanalysed for its hydrolysis atdifferent temperatures viz., 25 °C, 45 °C and 70 °C. Further, the effect of crosslinking, temperature and reaction time on catalytic activities of TRPUBs has been studied. TRPUBs grades have showna maximum swelling capacity up to 5200 %; excellent catalytic activity even at 70 °C; and 85 % activity retention after 18 days storage in buffer medium.

Study of Hydration Repulsion of Zwitterionic Polymer Brushes Resistant to Protein Adhesion through Molecular Simulations.

The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This investigation seeks to elucidate the correlation between the material composition and structural attributes of these polymer brushes in preventing protein adhesion. To achieve this goal, we modeled three different zwitterionic brushes, namely, carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl)-phosphorylcholine (MPC). The simulations revealed that elevating the grafting density enhances the structural stability, hydration strength, and resistance to protein adhesion exhibited by the polymer brushes. PCBMA manifests a more robust hydration layer, while PMPC demonstrates the slightest interaction with proteins. In a comprehensive evaluation, PSBMA polymer brushes emerged as the best choice with superior stability, enhanced protein repulsion, and minimally induced protein deformation, resulting in effective resistance to nonspecific adhesion. The high-density SBMA polymer brushes significantly reduce the level of protein adhesion in AFM testing. In addition, we have pioneered the quantitative characterization of hydration repulsion in polymer brushes by analyzing the hydration repulsion characteristics at different materials and graft densities. In summary, our study provides a nuanced understanding of the material and structural determinants influencing the capacity of zwitterionic polymer brushes to thwart protein adhesion. Additionally, it presents a quantitative elucidation of hydration repulsion, contributing to the advancement and application of antifouling polymer brushes.

Validation of a human saliva model for the determination of leachable monomers and other chemicals from dental materials.

This study aimed to prove the validity of a mixture of chemicals, including salts, small organic molecules, mucin, and α-amylase, as saliva surrogate ("artificial saliva") for assessing leakage of methacrylate monomers and other constituents from dental materials. To achieve this, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA), diurethane dimethacrylate (UDMA), bisphenol A glycerolate dimethacrylate (BisGMA), diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), bisphenol A (BPA), and five homologues of ethoxylated bisphenol A dimethacrylate (BisEMA EO2-6) in unstimulated and artificial saliva, and compared their concentrations in the two saliva media following either spiking with a mixture of the compounds or incubation of test specimens of printed biomaterials. Test specimens were immersed in unstimulated/artificial saliva, incubated at 37 °C for 24 h, and saliva aliquots were extracted with methanol and subsequently analyzed by LC-MS/MS. The method was validated with regard to matrix effects, linearity, selectivity, lower limits of quantification (LLOQ), precision, bias and combined measurement uncertainty (u'). The performance characteristics of the method were comparable for unstimulated and artificial saliva samples. The combined u' for individual chemicals at a concentration of 10 × LLOQ were within the range of 5.3-14 % for unstimulated saliva and 6.9-16 % for artificial saliva, except for the BisEMA homologues. Combined u' for the latter were 27-74 % in unstimulated saliva, and 27-79 % in artificial saliva. There was no detectable release of BPA from the test specimens, and the TPO concentrations were mainly below the LLOQ. TEGDMA and UDMA were detected in the highest quantities, and at comparable concentrations in the unstimulated and artificial saliva. For all BisEMA homologues, the release was higher in unstimulated saliva than in artificial saliva. The study showed that the artificial saliva model can be a suitable replacement for native saliva, but might underestimate leakage of more lipophilic methacrylates.

Bioinspired zwitterionic triblock copolymers designed for colloidal drug delivery: 1 - Synthesis and characterization.

This study describes the synthesis and characterization of triblock copolymers composed of poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-poly(propylene glycol)-block-poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC-b-PPG-b-PMPC) intended for, but not limited to, applications in colloidal drug delivery. Atom transfer radical polymerization led to a library of well-defined PMPC-b-PPG-b-PMPC triblock copolymers with varying overall molecular weight (ranging from ∼5 to ∼25 kDa) and composition (weight fraction of the hydrophobic PPG block ranged from ∼10 to ∼50 wt%). The properties of the synthesized triblock copolymers were linked to the PPG to bioinspired PMPC block(s) ratio, where the more hydrophilic species showed adequate aqueous solubility, surface activity and biocompatibility (non-toxicity) in in vitro cell culture. Their amphiphilic nature makes them adsorb efficiently onto polymer nanoparticles, what improves colloidal stability under stress conditions and, furthermore, depletes proteins from unwanted adsorption to the underlying surface. The current findings strengthen our insights into structure-function relationships of PMPC-based coatings leading to protecting shells on relevant polymer nanoparticle formulations. PMPC-b-PPG-b-PMPC triblock copolymers composed of a hydrophobic PPG block of 2-4 kDa flanked by two hydrophilic PMPC blocks each of 5-10 kDa seem to be most promising to enhance colloidal drug delivery vehicles.

In vitro development and optimization of cell-laden injectable bioprinted gelatin methacryloyl (GelMA) microgels mineralized on the nanoscale.

Bone defects may occur in different sizes and shapes due to trauma, infections, and cancer resection. Autografts are still considered the primary treatment choice for bone regeneration. However, they are hard to source and often create donor-site morbidity. Injectable microgels have attracted much attention in tissue engineering and regenerative medicine due to their ability to replace inert implants with a minimally invasive delivery. Here, we developed novel cell-laden bioprinted gelatin methacrylate (GelMA) injectable microgels, with controllable shapes and sizes that can be controllably mineralized on the nanoscale, while stimulating the response of cells embedded within the matrix. The injectable microgels were mineralized using a calcium and phosphate-rich medium that resulted in nanoscale crystalline hydroxyapatite deposition and increased stiffness within the crosslinked matrix of bioprinted GelMA microparticles. Next, we studied the effect of mineralization in osteocytes, a key bone homeostasis regulator. Viability stains showed that osteocytes were maintained at 98 % viability after mineralization with elevated expression of sclerostin in mineralized compared to non-mineralized microgels, showing that mineralization can effectively enhances osteocyte maturation. Based on our findings, bioprinted mineralized GelMA microgels appear to be an efficient material to approximate the bone microarchitecture and composition with desirable control of sample injectability and polymerization. These bone-like bioprinted mineralized biomaterials are exciting platforms for potential minimally invasive translational methods in bone regenerative therapies.

Hydrogels with dual sensitivity to temperature and pH in physiologically relevant ranges as supports for versatile controlled cell detachment.

Thermosensitive hydrogels based on the N-vinyl caprolactam (VCL), capable of allowing for cell adhesion and proliferation, as well as non-aggressive detachment by controlled temperature drop, were functionalized with 23 % or lower molar percentages of the cationizable hydrophobic unit 2-(diisopropylamino) ethyl methacrylate (DPAEMA), to obtain networks with dual sensitivity to temperature and pH. The swelling analysis of the systems has shown a transition pK (pKb) close to physiological values, dependent on the temperature of the medium (pKb of 6.6 and 6.9 when the temperature of the medium is above and below the transition temperature VPTT, respectively) and little dependence on the degree of functionalization of DPAEMA. In addition, at temperatures below the transition temperature (VPTT), the systems have shown large swelling variations as a function of the pH (i.e. below and above the pKb), exhibiting greater absorption capacity at pHs below pKb, where the DPAEMA units are cationized. Cytocompatibility and transplant capacity have been evaluated using the C166-GFP endothelial cell line. None of the thermosensitive hydrogels with variable DPAEMA content showed a delay with respect to the control without DPAEMA neither in terms of adhesion nor in proliferation. However, by increasing the percentage of DPAEMA functionalization -and decreasing thermosensitivity-, a correlative decrease in mitochondrial activity was obtained in the transplant, with significant differences for the hydrogels with DPAEMA molar percentage of 3 % or higher. Taking advantage of the proximity of the pKb to the physiological value, we have evaluated the cellular response and the capacity for transplantation after lowering the pH to 6.5, below pKb. A direct relationship of the DPAEMA functionalization degree on the detachment efficiency was observed, since the hydrogels with the highest molar load of DPAEMA showed higher mitochondrial metabolic activity after cell detachment.

Fabrication of silicon-based nickel nanoflower-encapsulated gelatin microspheres as an active antimicrobial carrier.

Local antibiotic application might mitigate the burgeoning problem of rapid emergence of antibiotic resistance in pathogenic microbes. To accomplish this, delivery systems must be engineered. Hydrogels have a wide range of physicochemical properties and can mimic the extracellular matrix, rendering them promising materials for local antibacterial agent application. Here, we synthesized antibacterial silicon (Si)-based nickel (Ni) nanoflowers (Si@Ni) and encapsulated them in gelatin methacryloyl (GelMA) using microfluidic and photo-crosslink technology, constructing uniform micro-sized hydrogel spheres (Si@Ni-GelMA). Si@Ni and Si@Ni-GelMA were characterized using X-ray diffraction, transmission electron microscopy, and scanning electron microscopy. Injectable Si@Ni-GelMA exhibited excellent antibacterial activities owing to the antibiotic effect of Ni against Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus, while showing negligible cytotoxicity. Therefore, the Si@Ni-GelMA system can be used as drug carriers owing to their injectability, visible light-mediated crosslinking, degradation, biosafety, and superior antibacterial properties.

Progress in cardiac tissue engineering and regeneration: Implications of gelatin-based hybrid scaffolds.

Cardiovascular diseases, particularly myocardial infarction (MI), remain a leading cause of morbidity and mortality worldwide. Current treatments for MI, more palliative than curative, have limitations in reversing the disease completely. Tissue engineering (TE) has emerged as a promising strategy to address this challenge and may lead to improved therapeutic approaches for MI. Gelatin-based scaffolds, including gelatin and its derivative, gelatin methacrylate (GelMA), have attracted significant attention in cardiac tissue engineering (CTE) due to their optimal physical and biochemical properties and capacity to mimic the native extracellular matrix (ECM). CTE mainly recruits two classes of gelatin/GelMA-based scaffolds: hydrogels and nanofibrous. This article reviews state-of-the-art gelatin/GelMA-based hybrid scaffolds currently applied for CTE and regenerative therapy. Hybrid scaffolds, fabricated by combining gelatin/GelMA hydrogel or nanofibrous scaffolds with other materials such as natural/synthetic polymers, nanoparticles, protein-based biomaterials, etc., are explored for enhanced cardiac tissue regeneration functionality. The engraftment of stem/cardiac cells, bioactive molecules, or drugs into these hybrid systems shows great promise in cardiac tissue repair and regeneration. Finally, the role of gelatin/GelMA scaffolds combined with the 3D bioprinting strategy in CTE will also be briefly highlighted.

Synthesis of a novel monomer "DDTU-IDI" for the development of low-shrinkage dental resin composites.

OBJECTIVE: The current dental resin composites often suffer from polymerization shrinkage, which can lead to microleakage and potentially result in recurring tooth decay. This study presents the synthesis of a novel monomer, (3,9-diethyl-1,5,7,11-tetraoxaspiro[5,5]undecane-3,9-diyl)bis(methylene) bis((2-(3-(prop-1-en-2-yl)phenyl)propan-2-yl)carbamate) (DDTU-IDI), and evaluates its effect in the formulation of low-shrinkage dental resin composites. METHODS: DDTU-IDI was synthesized through a two-step reaction route, with the initial synthesis of the required raw material monomer 3,9-diethyl-3,9-dihydroxymethyl-1,5,7,11-tetraoxaspiro-[5,5] undecane (DDTU). The structures were confirmed using Fourier-transform infrared (FT-IR) spectroscopy and hydrogen nuclear magnetic resonance (1HNMR) spectroscopy. Subsequently, DDTU-IDI was incorporated into Bis-GMA-based composites at varying weight percentages (5, 10, 15, and 20 wt%). The polymerization reaction, degree of conversion, polymerization shrinkage, mechanical properties, physicochemical properties and biocompatibility of the low-shrinkage composites were thoroughly evaluated. Furthermore, the mechanical properties were assessed after a thermal cycling test with 10,000 cycles to determine the stability. RESULTS: The addition of DDTU-IDI at 10, 15, and 20 wt% significantly reduced the polymerization volumetric shrinkage of the experimental resin composites, without compromising the degree of conversion, mechanical and physicochemical properties. Remarkably, at a monomer content of 20 wt%, the polymerization shrinkage was reduced to 1.83 ± 0.53%. Composites containing 10, 15, and 20 wt% DDTU-IDI exhibited lower water sorption and higher contact angle. Following thermal cycling, the composites exhibited no significant decrease in mechanical properties, except for the flexural properties. SIGNIFICANCE: DDTU-IDI has favorable potential as a component which could produce volume expansion and increase rigidity in the development of low-shrinkage dental resin composites. The development of low-shrinkage composites containing DDTU-IDI appears to be a promising strategy for reducing polymerization shrinkage, thereby potentially enhancing the longevity of dental restorations.

A heparin-functionalized bioink with sustained delivery of vascular endothelial growth factor for 3D bioprinting of prevascularized dermal constructs.

Skin tissue engineering faces challenges due to the absence of vascular architecture, impeding the development of permanent skin replacements. To address this, a heparin-functionalized 3D-printed bioink (GH/HepMA) was formulated to enable sustained delivery of vascular endothelial growth factor (VEGF), comprising 0.3 % (w/v) hyaluronic acid (HA), 10 % (w/v) gelatin methacrylate (GelMA), and 0.5 % (w/v) heparin methacrylate (HepMA). The bioink was then used to print dermal constructs with angiogenic functions, including fibroblast networks and human umbilical vein endothelial cell (HUVEC) networks. GH/HepMA, with its covalently cross-linked structure, exhibits enhanced mechanical properties and heparin stability, allowing for a 21-day sustained delivery of VEGF. Cytocompatibility experiments showed that the GH/HepMA bioink supported fibroblast proliferation and promoted collagen I production. With VEGF present, the GH/HepMA bioink promoted HUVEC proliferation, migration, as well as the formation of a richer capillary-like network. Furthermore, HA within the GH/HepMA bioink enhanced rheological properties and printability. Additionally, 3D-bioprinted dermal constructs showed significant deposition of collagen I and III and mature stable capillary-like structures along the axial direction. In summary, this study offers a promising approach for constructing biomimetic multicellular skin substitutes with angiogenesis-induced functions.

Hydrophobic association: A facile approach to prepare physical cross-linked gelatin hydrogel with desirable thermal stability, flexibility and self-healing ability.

Methacrylic anhydride was added to 20 % gelatin solution to prepare gelatin methacryloyl (GelMA) but an unexpected gelation process was observed within several minutes. The experimental data revealed that the methacryloyl substitution can increase the hydrophobicity of gelatin and the micellar diameter in solution. Therefore, we speculated that the methacryloyl substitution caused the formation of micellar cross-links based on the hydrophobic residues of gelatin and the methacryloyl groups, thus obtaining the hydrophobic association hydrogels. The thixotropic and tensile experiments confirmed that GelMA hydrogel possessed the features of hydrophobic association hydrogels like self-healing and stretchable abilities. The rheological experiments revealed that the gelation rate and the mechanical strength of the GelMA hydrogels were in direct proportion to the concentration of GelMA and the degree of methacryloyl substitution. GelMA hydrogels possessed desirable thermal stability that it didn't melt after being heated to 90 °C. Furthermore, the MTT assays and calcein AM/PI staining revealed that GelMA hydrogel was biocompatible. These results collectively confirm that the hydrophobic association is a prospective and facile approach to prepare gelatin hydrogel with desirable properties for further application.

Decellularized matrix bioink with gelatin methacrylate for simultaneous improvements in printability and biofunctionality.

Gelatin methacrylate (GelMA) bioink has been widely used in bioprinting because it is a printable and biocompatible biomaterial. However, it is difficult to print GelMA bioink without any temperature control because it has a thermally-sensitive rheological property. Therefore, in this study, we developed a temperature-controlled printing system in real time without affecting the viability of the cells encapsulated in the bioink. In addition, a skin-derived decellularized extracellular matrix (SdECM) was printed with GelMA to better mimic the native tissue environment compared with solely using GelMA bioink with the enhancement of structural stability. The temperature setting accuracy was calculated to be 98.58 ± 1.8 % for the module and 99.48 ± 1.33 % for the plate from 5 °C to 37 °C. The group of the temperature of the module at 10 °C and the plate at 20 °C have 93.84 % cell viability with the printable range in the printability window. In particular, the cell viability and proliferation were increased in the encapsulated fibroblasts in the GelMA/SdECM bioink, relative to the GelMA bioink, with a morphology that significantly spread for seven days. The gene expression and growth factors related to skin tissue regeneration were relatively upregulated with SdECM components. In the bioprinting process, the rheological properties of the GelMA/SdECM bioink were successfully adjusted in real time to increase printability, and the native skin tissue mimicked components providing tissue-specific biofunctions to the encapsulated cells. The developed bioprinting strategies and bioinks could support future studies related to the skin tissue reconstruction, regeneration, and other medical applications using the bioprinting process.

Advancing Peripheral Nerve Regeneration: 3D Bioprinting of GelMA-Based Cell-Laden Electroactive Bioinks for Nerve Conduits.

Peripheral nerve injuries often result in substantial impairment of the neurostimulatory organs. While the autograft is still largely used as the "gold standard" clinical treatment option, nerve guidance conduits (NGCs) are currently considered a promising approach for promoting peripheral nerve regeneration. While several attempts have been made to construct NGCs using various biomaterial combinations, a comprehensive exploration of the process science associated with three-dimensional (3D) extrusion printing of NGCs with clinically relevant sizes (length: 20 mm; diameter: 2-8 mm), while focusing on tunable buildability using electroactive biomaterial inks, remains unexplored. In addressing this gap, we present here the results of the viscoelastic properties of a range of a multifunctional gelatin methacrylate (GelMA)/poly(ethylene glycol) diacrylate (PEGDA)/carbon nanofiber (CNF)/gellan gum (GG) hydrogel bioink formulations and printability assessment using experiments and quantitative models. Our results clearly established the positive impact of the gellan gum on the enhancement of the rheological properties. Interestingly, the strategic incorporation of PEGDA as a secondary cross-linker led to a remarkable enhancement in the strength and modulus by 3 and 8-fold, respectively. Moreover, conductive CNF addition resulted in a 4-fold improvement in measured electrical conductivity. The use of four-component electroactive biomaterial ink allowed us to obtain high neural cell viability in 3D bioprinted constructs. While the conventionally cast scaffolds can support the differentiation of neuro-2a cells, the most important result has been the excellent cell viability of neural cells in 3D encapsulated structures. Taken together, our findings demonstrate the potential of 3D bioprinting and multimodal biophysical cues in developing functional yet critical-sized nerve conduits for peripheral nerve tissue regeneration.

Mechanical and Antimicrobial Properties of Boron Nitride/Methacrylic Acid Quaternary Ammonium Composites Reinforced Dental Flowable Resins.

Dental resin composites (DRCs) are commonly used to restore teeth affected by dental caries or defects. These materials must possess excellent properties to withstand the complex oral environment. The objective of this study was to prepare and characterize Boron nitride nanosheets (BNN)/ dimethyl amino hexadecyl methacrylate (DMAHDM) composites (BNN/DMA), and to evaluate them as functional fillers to enhance the mechanical and antimicrobial properties of dental resins. The BNN/DMA composites were successfully prepared under the theoretical guidance of molecular dynamics (MD), and then the physicochemical and morphological characterization of the BNN/DMA composites were carried out by using various test methods, such as FT-IR, XRD, UV-vis spectroscopy, SEM, TEM, and AFM. It was doped into the dental flowable resin in a certain proportion, and the results showed that the flexural strength (FS), elastic modulus (EM), compressive strength (CS), and microhardness (MH) of the modified resin composites were increased by 53.29, 47.8, 97.59, and 37.1%, respectively, with the addition of 0.8 wt % of BNN/DMA composite fillers. It has a good inhibition effect on Streptococcus mutans, with an inhibition rate as high as 90.43%. Furthermore, this effect persists even after one month of aging. In conclusion, the modification of flowable resins with low-concentration BNN/DMA composites favorably integrates the mechanical properties and long-term antimicrobial activity of dental resins. At the same time, they have good biocompatibility and do not affect the aesthetics. The BNN/DMA composite modified flowable resin has the potential to become a new type of antimicrobial dental restorative material.

A dual-crosslinking electroactive hydrogel based on gelatin methacrylate and dibenzaldehyde-terminated telechelic polyethylene glycol for 3D bio-printing.

Gelatin was widely used as scaffold materials in 3D bio-printing due to its excellent bioactivity and availability and especially that their arginine-glycine-aspartic acid (RGD) sequences could efficiently promote cell adhesion and proliferation. In this study, an electroactive and 3D bio-printable hydrogel was prepared through a two-step chemical cross-linking process. Specifically, residual free amino groups of methacrylated gelatin (GelMA) were cross-linked with the aldehyde groups of dibenzaldehyde-terminated telechelic polyethylene glycol (DF-PEG) via Schiff base bonds, forming a gel at 37 °C. During the subsequent 3D bio-printing process, GelMA underwent UV curing, forming a secondary cross-linked network to the mechanical strength and stability of the printed structure. The uniform dispersion of carbon nanotubes (CNTs) in the GelMA/DF-PEG composite hydrogel significantly increased its conductivity. The optimized GelMA/DF-PEG composite hydrogel, i.e., 30% GelMA and 25% DF-PEG (G30D25-CNTs), exhibited superior bio-printability. When the content of CNTs was above 4%, the conductivity of G30D25-CNTs hydrogel exceeded 10-2 S/m, which satisfied the needs of cells for micro-current stimulation. Furthermore, the pore microstructures, swelling behavior, degradation ability and cell toxicity of G30D25-CNTs electroactive hydrogels were thoroughly evaluated. Thus, the G30D25-CNTs hydrogel with 4% MWCNTs could be considered for further application in electrical stimulation of tissue regeneration such as muscle and cardiac nerve tissue repair.

Dentin surface modification by MDP to improve dentin bonding stability: Topological enhancement and mineralization of collagen structure in hybrid layers.

Decades of research have been conducted on 10-Methacryloyloxydecyl dihydrogen phosphate (MDP) through numerous studies. The mechanisms by which its residual calcium salts benefit dentin bonding remain undetermined. The objective of the research was to investigate the role and process of remaining calcium salts in the priming procedure and their capacity for remineralization. The investigation focused on the variations in topological structure, mechanical properties, and chemical interactions between the main agent and the dentin surface. Two adhesive modes including prime-and-rinse(P&R) and prime-and-nonrinse (P&NR) utilized to evaluate the bonding performance and remineralization ability. The findings indicated that both P&R and P&NR methods could eliminate the smear-layer, uncover dentinal-tubules, and generate a textured/rough surface on the dentin. Collagen fibrils exhibited a greater presence of inorganic minerals in the P&NR mode. Compared to control group, both P&R and P&NR groups improved immediate and aging bond strength significantly (P < 0.05). AFM and 3D-STORM revealed MDP and its residual calcium salts distributed in collagen fibrils and expanded collagen matrix. In the P&NR group, TEM revealed that the dentin collagen matrix experienced some remineralization, and there was also mineralization within the collagen fibrils embedded in the bonding interface. Thus, MDP priming improved dentin bonding stability. Residual calcium salts of P&NR process can enhance topological structure of the collagen matrix and induce intrafibrillar mineralization.

Deliver on a Promise: Hydrogen-Bonded Polymer Nanomedicine with a Precise Ratio of Chemodrug and Photosensitizer for Intelligent Cancer Therapy.

The outcomes of combined cancer therapy are largely related to loading content and contribution of each therapeutic agent; however, fine-tuning the ratio of two coloaded components toward precise cancer therapy is a great challenge and still remains in its infancy. We herein develop a supramolecular polymer scaffold to optimize the coloading ratio of chemotherapeutic agent and photosensitizer through hydrogen-bonding (H-bonding) interaction, for maximizing the efficacy of intelligent cancer chemo/photodynamic therapies (CT/PDT). To do so, we first synthesize a thymine (THY)-functionalized tetraphenylporphyrin photosensitizer (i.e., TTPP), featuring the same molecular configuration of H-bonding array with chemotherapeutic carmofur (e.g., 1-hexylcarbamoyl-5-fluorouracil, HCFU). Meanwhile, a six-arm star-shaped amphiphilic polymer vehicle P(DAPA-co-DPMA-co-OEGMA)6 (poly(diaminopyridine acrylamide-co-2-(diisopropylamino)ethyl methacrylate-co-oligo(ethylene glycol) monomethyl ether methacrylate)6) is prepared, bearing hydrophilic and biocompatible POEGMA segment, along with hydrophobic PDAPA and PDPMA segments, characterizing the randomly dispersed dual functionalities, i.e., heterocomplementary H-bonding DAP motifs and pH-responsive protonation DPMA content. Thanks to the identical DAP/HCFU and DAP/TTPP H-bonding association capability, the incorporation of both HCFU and TTPP to six-arm star-shaped P(DAPA-co-DPMA-co-OEGMA)6 vehicle, with an optimized coloading ratio, can be straightforwardly realized by adjusting the feeding concentrations, thus yielding the hydrogen-bonded supramolecular nanoparticles (i.e., HCFU-TTPP-SPNs), demonstrating the codelivery of two components with the promise to optimize the combined CT/PDT efficacy.

Composite Containing Calcium Phosphate Particles Functionalized with 10-MDP.

The phosphate ester monomer 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) is capable of bonding to hydroxyapatite and, for this reason, is a key component of several self-etch adhesives. In this study, dicalcium phosphate dihydrate particles (DCPD; CaHPO4.2H2O) were functionalized with 10-MDP and used to formulate an experimental composite with 50 vol% inorganic content (3:1 DCPD:silanated barium glass ratio) dispersed in a BisGMA/TEGDMA matrix. The tested hypothesis was that DCPD functionalization would improve the composite's mechanical performance without compromising Ca2+ release. Composites containing nonfunctionalized DCPD or only reinforcing glass (in both cases, with or without 10-MDP mixed in the resin phase) were used as controls. Materials were tested for degree of conversion (DC; by Fourier transform infrared spectroscopy), water sorption (WS) and solubility (SL; according to ISO 4049), biaxial flexural strength (BFS)/modulus (FM) after 24 h and 5 mo in water, and 28-d Ca2+ release in water (by plasma-coupled optical emission spectroscopy). Data were analyzed using analysis of variance/Tukey test (alpha: 5%). DCPD functionalization did not interfere with DC. The composite containing functionalized DCPD showed significantly lower WS and SL in comparison with the material formulated with nonfunctionalized particles. The presence of 10-MDP (as a functionalizing agent or dispersed in the resin phase) reduced the composite's initial BFS and FM. After 5 mo in water, the composite with functionalized DCPD and both glass-only composites were able to maintain their mechanical properties at levels statistically similar to what was observed after 24 h. Ca2+ release was significantly reduced in both formulations containing 10-MDP. In conclusion, DCPD functionalization with 10-MDP increased the composite's resistance to hydrolytic degradation, improving its mechanical stability after prolonged water storage. However, the impaired water transit at the particle-matrix interface led to a reduction in Ca2+ release.

Preparation of Block Copolymer Self-Assemblies via Pisa in a Non-Polar Medium Based on RCMP.

Polymerization-induced self-assembly (PISA) is conducted in a non-polar medium (n-dodecane) via reversible complexation-mediated polymerization (RCMP). Stearyl methacrylate (SMA) is used to synthesize a macroinitiator, and subsequent block polymerization of benzyl methacrylate (BzMA) from the macroinitiator in n-dodecane afforded a PSMA-PBzMA block copolymer, where PSMA is poly(stearyl methacrylate) and PBzMA is poly(benzyl methacrylate). Because PSMA is soluble but PBzMA is insoluble in n-dodecane, the block copolymer formed a self-assembly during the block polymerization (PISA). Spherical micelles, worms, and vesicles are obtained, depending on the degrees of polymerization of PSMA and PBzMA. "One-pot" PISA is also attained; namely, BzMA is directly added to the reaction mixture of the macroinitiator synthesis, and PISA is conducted in the same pot without purification of the macroinitiator. The spherical micelle and vesicle structures are also fixed using a crosslinkable monomer during PISA. RCMP-PISA is highly attractive as it is odorless and metal-free. The "one-pot" synthesis does not require the purification of the macroinitiator. RCMP-PISA can provide a practical approach to synthesize self-assemblies in non-polar media.

Conductive GelMA/alginate/polypyrrole/graphene hydrogel as a potential scaffold for cardiac tissue engineering; Physiochemical, mechanical, and biological evaluations.

Cardiac failure can be a life-threatening condition that, if left untreated, can have significant consequences. Functional hydrogel has emerged as a promising platform for cardiac tissue engineering. In the proposed study, gelatin methacrylate (GelMA) and alginate, as a primary matrix to maintain cell viability and proliferation, and polypyrrole and carboxyl-graphene, to improve mechanical and electrical properties, are thoroughly evaluated. Initially, a polymer blend of GelMA/Alginate (1:1) was prepared, and then the addition of 2-5 wt% of polypyrrole was evaluated. Next, the effect of incorporating graphene-carboxyl nanosheets (1, 2, and 3 wt%) within the optimized scaffold with 2 wt% polypyrrole was thoroughly studied. The electrical conductivity of the hydrogels was significantly enhanced from 0.0615 ± 0.007 S/cm in GelMA/alginate to 0.124 ± 0.04 S/cm with the addition of 5 wt% polypyrrole. Also, 3 wt% carboxyl graphene improved the electrical conductivity to 0.27 ± 0.09 S/cm. The compressive strength of carboxyl-graphene-containing hydrogel was in the range of 175 to 520 kPa, and tensile strength was 61 and 133 kPa. The simplicity and low-cost fabrication, tunable mechanical properties, optimal electrical conductivity, blood compatibility, and non-cytotoxicity of GelMA/alginate/polypyrrole/graphene biocomposite hydrogel is a promising construct for cardiac tissue engineering.