Functional Scaffolds Research Articles

Composite phase change materials based on CuS-coated carbonized melamine foam/reduced graphene oxide frameworks for multiple energy conversion and storage applications

The single function and leakage of organic phase change materials (OPCMs) used alone considerably limit the scope of their large-scale applications. An efficient method of addressing this issue is by adding functional fillers and porous scaffolds to OPCMs. In this study, a novel CuS-coated carbonized melamine foam (CMF)/reduced graphene oxide (rGO) framework (CMF/rGO/CuS) was developed for the preparation of stable multifunctional OPCMs. The functional materials rGO and CuS were used as reinforcing materials, and CMF was used as a supporting material. Paraffin wax (PW), a thermal storage substance, was encapsulated in the CMF/rGO/CuS framework by vacuum-assisted impregnation to obtain a PW@CMF/rGO/CuS composite with excellent comprehensive properties. When the concentration of the conductive filler CuS was 2.0 wt%, the conductivity of the PW@CMF/rGO/CuS 2.0was 73.7 % more than that of pure PW, and its photothermal conversion efficiency exceeded 90 %. Meanwhile, CMF/rGO/CuS endowed the composite with a thermal conductivity of 0.2525 W m−1 K−1, which was 33.6 % higher than that of pure PW. Finally, PW@CMF/rGO/CuS demonstrated high thermal cycling and thermal cycling stability with good application prospects in various fields.

Experimental and finite element analysis on the effect of pores on bio-printed polycaprolactone bone scaffolds

Bone scaffolds are three-dimensional biocompatible structure that mimics the properties of natural bone and is used in tissue engineering applications to help repair or regenerate bone tissue. In addition to acting as a temporary framework for the growth of new bone, it permits the infiltration of cells, nutrients, and blood vessels to speed up the healing process. The performance and use of bone scaffolds are greatly influenced by the design of their pores.Pore shapes in bone scaffolds play a crucial role in determining their functionality and performance.In the current study, bone scaffolds were fabricatedusing 3D printing and polycaprolactone material with various pore shapes, including circles, hexagons, squares, and triangles. SOLIDWORKS® 2023 was used to solid model the scaffolds with various pore shapes. Compression tests and finite element analysis using ANSYS WORKBENCH® 2023 were used to assess the mechanical properties of these scaffolds. The findings show that the circular pore shape performed better than its counter parts. This study advances our knowledge of the connection between pore shape and scaffold functionality, facilitating the design of better bone scaffolds for a varied applications.

Strain and Complexity, Passerini and Ugi Reactions of Four-Membered Heterocycles and Further Elaboration of TOSMIC Product.

Straightforward and general Passerini and Ugi procedures have been developed to incorporate four-membered heterocycles into highly functionalized scaffolds. Additionally, toslymethyl isocyanide (TosMIC)-derived Ugi adducts have been prepared, showcasing the prospect of the multicomponent reaction.

Printing tissue-engineered scaffolds made of polycaprolactone and nano-hydroxyapatite with mechanical properties appropriate for trabecular bone substitutes

BackgroundBone tissue engineering, based on three-dimensional (3D) printing technology, has emerged as a promising approach to treat bone defects using scaffolds. The objective of this study was to investigate the influence of porosity and internal structure on the mechanical properties of scaffolds.MethodsWe fabricated composite scaffolds (which aimed to replicate trabecular bone) from polycaprolactone (PCL) reinforced with 30% (wt.) nano-hydroxyapatite (nHAp) by extrusion printing. Scaffolds with various porosities were designed and fabricated with and without an interlayer offset, termed as staggered and lattice structure, respectively. Mechanical compressive testing was performed to determine scaffold elastic modulus and yield strength. Linear regression was used to evaluate mechanical properties as a function of scaffold porosity.ResultsDifferent relationships between mechanical properties and porosities were noted for the staggered and lattice structures. For elastic moduli, the two relationships intersected (porosity = 55%) such that the lattice structure exhibited higher moduli with porosity values greater than the intersection point; vice versa for the staggered structure. The lattice structure exhibited higher yield strength at all porosities. Mechanical testing results also indicated elastic moduli and yield strength properties comparable to trabecular bone (elastic moduli: 14–165 MPa; yield strength: 0.9–10 MPa).ConclusionsTaken together, this study demonstrates that scaffolds printed from PCL/30% (wt.) nHAp with lattice and staggered structure offer promise for treating trabecular bone defects. This study identified the effect of porosity and internal structure on scaffold mechanical properties and provided suggestions for developing scaffolds with mechanical properties for substituting trabecular bone.

Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan.

Across eukaryotic proteomes, tryptophan is the least abundant of the 20 canonical amino acids, which makes it an ideal chemical handle for the late-stage functionalization of peptide and protein scaffolds with minimal production of undesired isoforms. Herein, we report the photocatalytic C2-alkylation of tryptophan using bromodifluoroacetate/acetamide-derived radical precursors. This rapid visible-light-mediated reaction is additive-free, operationally simple, and tolerates diverse functionality. We demonstrate the late-stage modification of a variety of complex peptides, including examples of biological significance.

Direct Ink Writing of Alginate–Gelatin Hydrogel: An Optimization of Ink Property Design and Printing Process Efficacy

Direct Ink Writing (DIW), which is widely used for developing functional 3D scaffolds that have robust structural integrity for the growth of target tissues/cells, has emerged as an appealing method for biomedical applications. The production of 3D structures involves three separate but interconnected stages (material development, printing process, and post-printing treatment), whose effectiveness is influenced by several factors that therefore make it challenging to optimize the entire procedure. By studying the material processability and leveling the printing settings, this study proposes a three-step method to enhance the ink property design and the printer’s performance. The recommended approach is focused on the thorough study of alginate–gelatin hydrogel properties, which is a commonly used ink in biomedical applications, due to its natural origin through marine flora, as well as the development process parameters and their intercorrelations. Principal Component Analysis in comparison with K-means clustering was applied to reveal material properties that are highly correlated with additive manufacturing (AM) processability, and Taguchi’s Design of Experiments (DOE) determined the printing settings (primary and secondary) for achieving optimum printing accuracy. PCA results were affirmed by K-means clustering and showed that viscosity, m, G′ and G″ govern blends’ printing behavior while application of DOE led to 85% pore area printability.

Perfusion and Ultrasonication Produce a Decellularized Porcine Whole-Ovary Scaffold with a Preserved Microarchitecture.

The application of decellularized scaffolds for artificial tissue reconstruction has been an approach with great therapeutic potential in regenerative medicine. Recently, biomimetic ovarian tissue reconstruction was proposed to reestablish ovarian endocrine functions. Despite many decellularization methods proposed, there is no established protocol for whole ovaries by detergent perfusion that is able to preserve tissue macro and microstructure with higher efficiency. This generated biomaterial may have the potential to be applied for other purposes beyond reproduction and be translated to other areas in the tissue engineering field. Therefore, this study aimed to establish and standardize a protocol for porcine ovaries' decellularization based on detergent perfusion and ultrasonication to obtain functional whole-ovary scaffolds. For that, porcine ovaries (n = 5) were perfused with detergents (0.5% SDS and 1% Triton X-100) and submitted to an ultrasonication bath to produce acellular scaffolds. The decellularization efficiency was evaluated by DAPI staining and total genomic DNA quantification. ECM morphological evaluation was performed by histological, immunohistochemistry, and ultrastructural analyses. ECM physico-chemical composition was evaluated using FTIR and Raman spectroscopy. A cytocompatibility and cell adhesion assay using murine fibroblasts was performed. Results showed that the proposed method was able to remove cellular components efficiently. There was no significant ECM component loss in relation to native tissue, and the scaffolds were cytocompatible and allowed cell attachment. In conclusion, the proposed decellularization protocol produced whole-ovaries scaffolds with preserved ECM composition and great potential for application in tissue engineering.

Exploring Regio- and Stereoselectivity in [3+2] Cycloaddition: Molecular Electron Density Theory Approach for Novel Spirooxindole-Based Benzimidazole with Pyridine Spacer

A new ethylene derivative was synthesized as a precursor for the [3+2] cycloaddition (32CA) reaction to access a novel spirooxindole embodied with benzimidazole with a pyridine spacer. The chalcone derivatives 3a–j is obtained with condensation of the acetyl derivative with aryl aldehydes. The one-pot multi-component reaction of the ethylene derivative, 5-Cl-isatin, and octahydroindole-2-carboxylic acid enables the construction of a highly functionalized quaternary center spirooxindole scaffold in a high chemical yield. A study using the Molecular Electron Density Theory (MEDT) explains the complete regio- and stereoselectivity of the reaction, resulting in the exclusive formation of the ortho/endo-cycloadduct under kinetic control. The low activation Gibbs free energy is the result of the supernucleophilic character of the in situ-generated azomethine ylide and the strong electrophilic character of the ethylene derivatives.

Functionalization of Pyridine and Quinoline Scaffolds by Using Organometallic Li‐, Mg‐ and Zn‐Reagents

AbstractThis Review discusses the various methods for functionalizing pyridine and quinoline scaffolds, including direct selective metalation (DoM), halogen/metal exchange reactions, Li, Mg, and Zn insertion, and trans‐metalation approaches, which are then followed by cross‐coupling reactions of the Kumada or Negishi types. Selective deprotonation of aryl or pyridyl/quinolinyl derivatives can be performed using n‐BuLi, LDA, and TMP‐based different organolithium, ‐magnesium, and ‐zinc reagents. The functionalized pyridine and quinoline‐based heterocyclic compounds were prepared by selectively deprotonating with presenting a directing functional group substituted pyridine/quinoline analogues in the presence of TMP‐bases (TMP−Li, Mg, Zn reagents). Different aryl or alkyl Li, Mg, and Zn reagents with electron‐donating and electron‐withdrawing substituents undergo transition metal‐catalyzed C(sp2)−C(sp2) and C(sp2)−C(sp3) types of cross‐coupling reactions with pyridine/quinoline halides under mild conditions with the sustainable process producing complex N‐heterocycles. Using moderate and sustainable reaction conditions, sensitive functional group tolerance, and inexpensive and low toxic chemicals, highly functionalization of pyridine and quinoline‐based bioactive therapeutic scaffolds and natural products was accomplished. Therefore, in this article, we provide a succinct overview of the numerous synthetic strategies and practical methods used by various authors between 2010 and 2023 to functionalize pyridine and quinoline analogues using diverse Li, Mg, and Zn organometallic reagents.

Revolutionizing the Use of Honeybee Products in Healthcare: A Focused Review on Using Bee Pollen as a Potential Adjunct Material for Biomaterial Functionalization.

The field of biomedical engineering highly demands technological improvements to allow the successful engraftment of biomaterials requested for healing damaged host tissues, tissue regeneration, and drug delivery. Polymeric materials, particularly natural polymers, are one of the primary suitable materials employed and functionalized to enhance their biocompatibility and thus confer advantageous features after graft implantation. Incorporating bioactive substances from nature is a good technique for expanding or increasing the functionality of biomaterial scaffolds, which may additionally encourage tissue healing. Our ecosystem provides natural resources, like honeybee products, comprising a rich blend of phytochemicals with interesting bioactive properties, which, when functionally coupled with biomedical biomaterials, result in the biomaterial exhibiting anti-inflammatory, antimicrobial, and antioxidant effects. Bee pollen is a sustainable product recently discovered as a new functionalizing agent for biomaterials. This review aims to articulate the general idea of using honeybee products for biomaterial engineering, mainly focusing on describing recent literature on experimental studies on biomaterials functionalized with bee pollen. We have also described the underlying mechanism of the bioactive attributes of bee pollen and shared our perspective on how future biomedical research will benefit from the fabrication of such functionalized biomaterials.

Antibacterial Thermosensitive Silver-Hydrogel Nanocomposite Improves Wound Healing.

Bacterial infection and poor cell recruitment are among the main factors that prolong wound healing. To address this, a strategy is required that can prevent infection while promoting tissue repair. Here, we have created a silver nanoparticle-based hydrogel composite that is antibacterial and provides nutrients for cell growth, while filling cavities of various geometries in wounds that are difficult to reach with other dressings. Silver nanoparticles (AgNPs) were synthesized by chemical reduction and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and inductively coupled plasma-mass spectroscopy (ICP-MS). Using varying concentrations of AgNPs (200, 400, and 600 ppm), several collagen-based silver-hydrogel nanocomposite candidates were generated. The impact of these candidates on wound healing was assessed in a rat splinted wound model, while their ability to prevent wound infection from a contaminated surface was assessed using a rat subcutaneous infection model. Biocompatibility was assessed using the standard MTT assay and in vivo histological analyses. Synthesized AgNPs were spherical and stable, and while hydrogel alone did not have any antibacterial effect, AgNP-hydrogel composites showed significant antibacterial activity both in vitro and in vivo. Wound healing was found to be accelerated with AgNP-hydrogel composite treatment, and no negative effects were observed compared to the control group. The formulations were non-cytotoxic and did not differ significantly in hematological and biochemical factors from the control group in the in vivo study. By presenting promising antibacterial and wound healing activities, silver-hydrogel nanocomposite offers a safe therapeutic option that can be used as a functional scaffold for an acceleration of wound healing.

Scaffolds for drug delivery and tissue engineering: The role of genetics.

Scaffolds are implants commonly used to deliver cells, drugs, and genes into the body. Their regular porous structure ensures the proper support for cell attachment, proliferation, differentiated function, and migration. Techniques to fabricate a scaffold include leaching, freeze-drying, supercritical fluid technology, thermally induced phase separation, rapid prototyping, powder compaction, sol-gel, and melt molding. Gene delivery from the scaffold represents a versatile approach to influence the environment for managing cell function. Scaffolds can be used for various tissue engineering purposes, e.g. bone formation, periodontal regeneration, cartilage development, artificial corneas, heart valves, tendon repair, or ligament replacement. Moreover, they are also instrumental in cancer therapy, inflammation, diabetes, heart disease, and wound dressings. Scaffolds provide a platform to extend the delivery of drugs and genetic materials at a controlled timeframe, besides potentially being used to prevent infection upon surgery and other chronic diseases, provided that they can be formulated with specific medicines. This review discusses the need to design advanced functional scaffolds with the potential for modified drug delivery and tissue engineering in a synergistic approach. Special attention is given to works published in 2023 to generate the bibliometric map.

Chemoproteomic identification of a DPP4 homolog in Bacteroides thetaiotaomicron.

Serine hydrolases have important roles in signaling and human metabolism, yet little is known about their functions in gut commensal bacteria. Using bioinformatics and chemoproteomics, we identify serine hydrolases in the gut commensal Bacteroides thetaiotaomicron that are specific to the Bacteroidetes phylum. Two are predicted homologs of the human dipeptidyl peptidase 4 (hDPP4), a key enzyme that regulates insulin signaling. Our functional studies reveal that BT4193 is a true homolog of hDPP4 that can be inhibited by FDA-approved type 2 diabetes medications targeting hDPP4, while the other is a misannotated proline-specific triaminopeptidase. We demonstrate that BT4193 is important for envelope integrity and that loss of BT4193 reduces B. thetaiotaomicron fitness during in vitro growth within a diverse community. However, neither function is dependent on BT4193 proteolytic activity, suggesting a scaffolding or signaling function for this bacterial protease.

Pyridine C(sp2)-H bond functionalization under transition-metal and rare earth metal catalysis.

Pyridine is a crucial heterocyclic scaffold that is widely found in organic chemistry, medicines, natural products, and functional materials. In spite of the discovery of several methods for the synthesis of functionalized pyridines or their integration into an organic molecule, new methodologies for the direct functionalization of pyridine scaffolds have been developed during the past two decades. In addition, transition-metal-catalyzed C-H functionalization and rare earth metal-catalyzed reactions have flourished over the past two decades in the development of functionalized organic molecules of concern. In this review, we discuss recent achievements in the transition-metal and rare earth metal-catalyzed C-H bond functionalization of pyridine and look into the mechanisms involved.

DIPG-53. LSD1 DEGRADATION SYNERGIZES WITH HDAC INHIBITION IN PEDIATRIC H3K27M DIFFUSE MIDLINE GLIOMA

Abstract H3K27M-mutated diffuse midline glioma (H3K27M DMG) is an aggressive, lethal pediatric brain tumor which resists conventional cancer treatments. To identify new therapeutic targets, our lab executed a focused CRISPR negative selection screen in patient-derived H3K27M cell lines after treatment with the histone deacetylase (HDAC) inhibitor panobinostat, and discovered a strong co-dependence with the histone demethylase LSD1. We further explored the therapeutic potential of this synergistic interaction with a screen of HDAC- and LSD1- targeting drugs to identify synergistic combinations, which show penetration of the blood brain barrier suitable for clinical translation. Interestingly, conventional catalytic LSD1 inhibitors did not seem to synergize with HDAC inhibitors tested on cell viability, while a recently described CoREST/LSD1 degrader phenocopied the effects seen in our CRISPR screen. We hypothesized that the CoREST/LSD1 degrader induces synergy with HDAC inhibitors through elimination of a scaffolding function of LSD1. To prove this, we knocked out LSD1 using CRISPR/Cas9 in H3K27M cells and subsequently treated with a panel of HDAC inhibitors. These showed a significant sensitization compared to controls cells. Further, we confirm the high specificity of the CoREST/LSD1 degrader by performing streptavidin bead pull down with a newly synthesized biotin-conjugated probe. This revealed that it interacts with the entire CoREST complex (members include LSD1, RCOR1, HDAC1/2). In conclusion, we show that degrading CoREST/LSD1 in combination with HDAC inhibition is a synergistic strategy in H3K27M DMG. For future translational studies, we will assess biomarkers upon treatment and analyse compound potency in vivo.

Quantitative analysis of bone regeneration efficacy as shape conformity of scaffold: Evidence for importance of additive-manufacturing precision in tissue engineering

Additive manufacturing (AM) of customized scaffolds has been actively studied in tissue engineering. Most studies have focused on the functionalization of scaffolds for osteoinduction and osteoconduction for bone regeneration. However, in our previous study, we found that shape conformity between a defect and the scaffold was also a major factor with regard to enhancing bone regeneration. Thus, in this study, we performed a quantitative analysis of the shape conformity between the defect and scaffold using several novel experimental scaffolds. Employing several scaffolds with different conformities that increased linearly, the degree of bone regeneration was analyzed through new bone volume measurements and a histological analysis in conjunction with an in vivo experiment using rat calvaria. For the quantitative analysis, we compared the new bone volume reconstructed from a three-dimensional model based on CT data. New bone maturation was analyzed with respect to shape conformity through a histological analysis. Proliferation, maturation, and new bone formation were promoted by scaffold shape conformity. Thus, for bone regeneration, the AM precision and the fabrication technique are critical as the shape conformity of the scaffold to the bone defect is highly dependent on AM fabrication errors.

A Hierarchical 3D Graft Printed with Nanoink for Functional Craniofacial Bone Restoration

AbstractAn ideal craniofacial bone repair graft shall not only focus on the repair ability but also the regeneration of natural architecture with occlusal loads‐related function restoration. However, such functional bone tissue engineering scaffold has rarely been reported. Herein, a hierarchical 3D graft is proposed for rebuilding craniofacial bone with both natural structure and healthy biofunction reconstruction. Inspired by the bone healing process, an organic–inorganic nanoink with ultrasmall calcium phosphate oligomers and bone morphogenetic protein‐2 incorporated is developed for spatiotemporal guidance of new bone. Based on such homogeneous nanoink, a biomimetic graft, including a cortical layer containing Haversian system, and a cancellous layer featured with triply periodic minimum surface macrostructures, is fabricated via projection‐based 3D printing method, and the layers are loaded with distinct concentrations of bioactive factors for regenerating new bone with gradient density. The graft exhibits excellent osteogenic and angiogenic potential in vitro, and accelerates revascularization and reconstructs neo‐bone with original morphology in vivo. Benefiting from such natural architecture, loading force is widely transferred with reduced stress concentration around the inserted dental implant. Taken from native physiochemical and structural cues, this wstudy provides a novel strategy for functional tissue engineering through designing function‐oriented biomaterials.

Polydopamine-coated biomimetic bone scaffolds loaded with exosomes promote osteogenic differentiation of BMSC and bone regeneration.

The repair of bone defects is ideally accomplished with bone tissue engineering. Recent studies have explored the possibility of functional modification of scaffolds in bone tissue engineering. We prepared an SF-CS-nHA (SCN) biomimetic bone scaffold and functionally modified the scaffold material by adding a polydopamine (PDA) coating loaded with exosomes (Exos) of marrow mesenchymal stem cells (BMSCs). The effects of the functional composite scaffold (SCN/PDA-Exo) on BMSC proliferation and osteogenic differentiation were investigated. Furthermore, the SCN/PDA-Exo scaffolds were implanted into animals to evaluate their effect on bone regeneration. SCN biomimetic scaffolds were prepared by a vacuum freeze-drying/chemical crosslinking method. A PDA-functionalized coating loaded with BMSC-Exos was added by the surface coating method. The physical and chemical properties of the functional composite scaffolds were detected by scanning electron microscopy (SEM), energy spectrum analysis and contact angle tests. Invitro, BMSCs were inoculated on different scaffolds, and the Exo internalization by BMSCs was detected by confocal microscopy. The BMSC proliferation activity and cell morphology were detected by SEM, CCK-8 assays and phalloidin staining. BMSC osteogenic differentiation was detected by immunofluorescence, alizarin red staining and qRT‒PCR. Invivo, the functional composite scaffold was implanted into a rabbit critical radial defect model. Bone repair was detected by 3D-CT scanning. HE staining, Masson staining, and immunohistochemistry were used to evaluate bone regeneration. Compared with the SCN scaffold, the SCN/PDA-Exo-functionalized composite scaffold had a larger average surface roughness and stronger hydrophilicity. Invitro, the Exos immobilized on the SCN/PDA-Exo scaffolds were internalized by BMSCs. The BMSC morphology, proliferation ability and osteogenic differentiation effect in the SCN/PDA-Exo group were significantly better than those in the other control groups (p<0.05). The effects of the SCN/PDA-Exo functional composite scaffold on bone defect repair and new bone formation were significantly better than those of the other control groups (p<0.05). In this study, we found that the SCN/PDA-Exo-functionalized composite scaffold promoted BMSC proliferation and osteogenic differentiation invitro and improved bone regeneration efficiency invivo. Therefore, combining Exos with biomimetic bone scaffolds by functional PDA coatings may be an effective strategy for functionally modifying biological scaffolds.

The Synergistic Healing Function of Regular Treadmill Exercise and Nanofibrous Scaffolds on Peripheral Nervous System Injury: An In Vitro and In Vivo Study

In the current study, injured peripheral nerves were treated with a regular treadmill exercise program in combination with a nanofibrous neural channels loaded with arctium lappa extract (ALE). In Vitro studies showed that the neural channels were biocompatible and potentially facilitated gas exchange through the scaffolds. In addition, the produced scaffolds modulated the inflammatory responses. In Vivo study showed that the animals treated with both exercise and neural channels had the highest rate of functional recovery and histopathological restorations.

Multicomponent Approaches Involving Carbon Disulfide

AbstractIn present scenario, innovative carbon disulfide‐involving multicomponent protocols are extremely advantageous for practical and efficient construction of acyclic as well as heterocyclic building blocks. Carbon disulfide is well recognized synthetic component and has achieved the desirability of scientific community for the preparation of a variety of highly functionalized organic scaffolds. Carbon disulfide involving MCRs mostly advantage from other features such as bond‐forming efficiency, resource effectiveness, the use of easily obtainable starting compounds, and atom‐economy, which make these protocols useful environmentally benign alternatives, in care with the greener way in which organic chemistry is going on. In this review article, we have discussed the noteworthy topical advances in the promising region of carbon disulfide‐involving multicomponent reactions. It highlight the prospects and confronts, emphasizing the diverse approaches established previously.