Macroporous Scaffolds Research Articles

Electrospun "Hard-Soft" Interpenetrating Nanofibrous Tissue Scaffolds Facilitating Enhanced Mechanical Strength and Cell Proliferation.

"Soft" hydrogel-based macroporous scaffolds have been widely used in tissue engineering and drug delivery applications due to their hydrated interfaces and macroporous structures, but have drawbacks related to their weak mechanics and often weak adhesion to cells. In contrast, "hard" poly(caprolactone) (PCL) electrospun fibrous networks have desirable mechanical strength and ductility but offer minimal interfacial hydration and thus limited capacity for cell proliferation. Herein, we demonstrate the fabrication of interpenetrating nanofibrous networks based on coelectrospun PCL and poly(oligoethylene glycol methacrylate) (POEGMA) nanofibers that exhibit the mechanical benefits of PCL but the interfacial hydration benefits of hydrogels. The electrospinning process results in partially aligned but interpenetrating fiber network with minimal internal phase separation, leading to anisotropic but strong mechanical properties even in the hydrated state; apparent ultimate tensile strengths of the swollen scaffolds ranged from 429 ± 39 kPa in the direction of fiber alignment (longitudinal) to 86 ± 25 kPa perpendicular to fiber alignment (cross-longitudinal), typical of PCL-based scaffolds and enabling efficient suture retention in different directions. However, contact angle measurements indicate hydrogel-like interfacial properties due to the presence of the interpenetrating POEGMA network. C2C12 myoblast proliferation in the PCL-POEGMA scaffolds was 50% higher than that observed on PCL-only scaffolds, a result attributed to the presence of the more hydrophilic POEGMA interpenetrating nanofiber network. Overall, this method is demonstrated to represent a facile single-step strategy to fabricate strong macroporous but still interfacially hydrophilic scaffolds for tissue engineering applications.

Benefits of In Situ Foamed and Printed Porous Scaffolds in Wound Healing.

Macroporous hydrogels have shown significant promise in biomedical applications, particularly regenerative medicine, due to their enhanced nutrient and waste permeability, improved cell permissibility, and minimal immunogenicity. However, traditional methods of generating porous hydrogels require secondary post-processing steps or harmful reagents making simultaneous fabrication with bioactive factors and cells impossible. Therefore, a handheld printer is engineered for facile and continuous generation and deposition of hydrogel foams directly within the skin defect to form defect-specific macroporous scaffolds. Within the handheld system, a temperature-controlled microfluidic homogenizer is coupled with miniaturized liquid and air pumps to mix sterile air with gelatin methacryloyl (GelMA) at the desired ratio. An integrated photocrosslinking unit is then utilized to crosslink the printed foam in situ to form scaffolds with controlled porosity. The system is optimized to form reliable and uniform GelMA foams. The resulting foam scaffolds demonstrate mechanical properties with excellent flexibility making them suitable for wound healing applications. The results of in vitro cell culture on the scaffolds demonstrate significantly increased cellular activity compared to the solid hydrogel. The in vivo printed foam scaffolds enhanced the rate and quality of wound healing in mice with full-thickness wound without the use of biological materials.

Nucleation of Bioactive Hydroxyapatite on Polydopamine Coating Three-Dimensional Printed Poly (Lactic Acid) Macro-Porous Scaffold for Bone Grafting Application

Nucleation of Bioactive Hydroxyapatite on Polydopamine Coating Three-Dimensional Printed Poly (Lactic Acid) Macro-Porous Scaffold for Bone Grafting Application

Emulsion-Templated Gelatin/Amino Acids/Chitosan Macroporous Hydrogels with Adjustable Internal Dimensions for Three-Dimensional Stem Cell Culture.

The demand for macroporous hydrogel scaffolds with interconnected porous and open-pore structures is crucial for advancing research and development in cell culture and tissue regeneration. Existing techniques for creating 3D porous materials and controlling their porosity are currently constrained. This study introduces a novel approach for producing highly interconnected aspartic acid-gelatin macroporous hydrogels (MHs) with precisely defined open pore structures using a one-step emulsification polymerization method with surface-modified silica nanoparticles as Pickering stabilizers. Macroporous hydrogels offer adjustable pore size and pore throat size within the ranges of 50 to 130 μm and 15 to 27 μm, respectively, achieved through variations in oil-in-water ratio and solid content. The pore wall thickness of the macroporous hydrogel can be as thin as 3.37 μm and as thick as 6.7 μm. In addition, the storage modulus of the macroporous hydrogels can be as high as 7250 Pa, and it maintains an intact rate of more than 92% after being soaked in PBS for 60 days, which is also good performance for use as a biomedical scaffold material. These hydrogels supported the proliferation of human dental pulp stem cells (hDPSCs) over a 30 day incubation period, stretching the cell morphology and demonstrating excellent biocompatibility and cell adhesion. The combination of these desirable attributes makes them highly promising for applications in stem cell culture and tissue regeneration, underscoring their potential significance in advancing these fields.

Effective Young’s modulus of highly porous 3D printed mono-material and coaxial structures

The dynamic elastic response of 3D macroporous scaffolds is crucial to determine their performance under operating conditions. In this work, the elastic behaviour of 3D printed bar-shaped scaffolds of γ-Al2O3 and γ-Al2O3/graphene nanoplatelets (GNP) composites (18 vol%), fabricated by Direct Ink Writing (DIW), is investigated. Dynamic Young’s modulus (E) is studied by the Impulse Excitation Technique (IET) and compared with theoretical results obtained by Finite Element Methods (FEM) and the multi-scale material simulator GeoDict®. In addition, Resonant Ultrasound Spectroscopy (RUS) is used to characterize E of single- and bi-material coaxial struts. While additions of GNP to γ-Al2O3 lead to an increase in E, it decreases in the coaxial struts due to the development of thermal residual stresses at the core/shell interface. The suitability of combining experimental and theoretical methods for the analysis of the elastic properties and the anisotropy associated with the lattice pattern is demonstrated.

Tissue Regeneration in Infected Wounds of Albino Rats Using Ciprofloxacin-Loaded Gelatin Microspheres Incorporated Collagen Scaffold: A Histological Approach with H&E Staining

A wound care system consisting of ciprofloxacin-loaded gelatin microspheres impregnated in a macroporous collagen scaffold was created to effectively control wound infection and regenerate soft tissue at the wound site. Histological and biochemical alterations were observed in infected wounds treated with these scaffolds in Albino Wistar rats. Furthermore, the study examined the immediate and prolonged release of ciprofloxacin from the scaffolds, as well as their function in eliminating bacterial infections and expediting the process of skin healing and regeneration. The developed technique was followed in the streamlined process of creating these collagen scaffolds. Compared to untreated wounds, the group receiving scaffold treatment experienced a faster rate of wound closure. It was noted that the rate of infections was considerably reduced and that full soft tissue regeneration occurred within 12 days. The development of well-deposited collagen bundles in the treated groups was demonstrated by H&E staining, which verified the flawless regeneration of the dermis and epidermis. The antimicrobial agent-loaded gelatin microspheres impregnated into the porous collagen scaffold demonstrated remarkable soft tissue regeneration and efficient infection control at the wound site.

Influence of Hydroxyapatite Content on Physical and Rheological Properties of Chitosan-based Scaffold

Chitosan-based scaffolds offer significant potential in tissue engineering and regenerative medicine. Whilst exhibiting great bio-regenerative and biocompatible properties, their mechanical properties remain quite poor. The presented research is focused on the modification of macroporous chitosan scaffolds with various amounts of bioactive ceramics (hydroxyapatite) and its influence on the physical and rheological properties of the composite scaffold. Chitosan/hydroxyapatite composite scaffolds with a highly porous microstructure have been prepared by suspending hydroxyapatite (HAp) particles into the chitosan matrix. According to SEM imaging, homogeneous dispersion of the inorganic phase in a chemically-crosslinked chitosan matrix had been achieved. The obtained composite scaffolds exhibited lower swelling capacity with respect to pure chitosan after 24 h of incubation in Hanks’ balanced salt solution. Rheological measurements show an increase in storage and loss modulus indicating an improvement in mechanical properties under shear stress. Furthermore, no significant change in loss factor (tanδ) was observed indicating no change in composite viscoelastic properties with an increase in HAp content.

Implantable CAR T cell factories enhance solid tumor treatment

Chimeric Antigen Receptor (CAR) T cell therapy has produced revolutionary success in hematological cancers such as leukemia and lymphoma. Nonetheless, its translation to solid tumors faces challenges due to manufacturing complexities, short-lived in vivo persistence, and transient therapeutic impact. We introduce 'Drydux' - an innovative macroporous biomaterial scaffold designed for rapid, efficient in-situ generation of tumor-specific CAR T cells. Drydux expedites CAR T cell preparation with a mere three-day turnaround from patient blood collection, presenting a cost-effective, streamlined alternative to conventional methodologies. Notably, Drydux-enabled CAR T cells provide prolonged in vivo release, functionality, and enhanced persistence exceeding 150 days, with cells transitioning to memory phenotypes. Unlike conventional CAR T cell therapy, which offered only temporary tumor control, equivalent Drydux cell doses induced lasting tumor remission in various animal tumor models, including systemic lymphoma, peritoneal ovarian cancer, metastatic lung cancer, and orthotopic pancreatic cancer. Drydux's approach holds promise in revolutionizing solid tumor CAR T cell therapy by delivering durable, rapid, and cost-effective treatments and broadening patient accessibility to this groundbreaking therapy.

Fabrication of Bioglass 58S 3D macroporous scaffolds, using a PMMA monolith template, to improve cell viability

Bioglass 58S is a bioactive material that can be used to help bone regeneration. In this article we present the fabrication of macroporous 58S Bioglass scaffolds with 3D interconnected porosity, that were prepared by immersing a PMMA microsphere monolith into a 58S sol. The resulting composite samples were calcined leaving macroporous 58S BG scaffolds, which were characterized by SEM, DSC-TGA, XRD and FTIR spectroscopy. These were compared to 58S Bioglass powders prepared using the same sol and calcined under the same conditions. Apart from the presence of macropores, the main difference between the two types of Bioglass 58S samples was the presence of carbonate species in the samples prepared using the PMMA monolith. Finally, the bioactivity of the macroporous 58S scaffolds and 58S powders were evaluated using SBF and cell viability assays. The macroporous 58S scaffolds were found to greatly improve the cell viability compared to the 58S powders which could be attributed to the presence of carbonate species.

Design and characterization of 3D printed pore gradient hydrogel scaffold for bone tissue engineering

Macroporous hydrogel scaffolds are widely used in tissue engineering to promote cell growth and proliferation. Aiming to enhance cell seeding efficiency and facilitate the osteodifferentiation of mesenchymal stem cells, this study demonstrates the fabrication of pore gradient biodegradable hydrogel scaffolds inspired by natural bone structure for bone tissue engineering applications. The scaffolds were fabricated via extrusion-based 3D printing, using sequential deposition of three customized Gelatin/Oxidized Alginate - based inks with subsequent cryogenic crosslinking for permanent structure fixation. The resulting constructs were characterized and featured a continuous gradient morphology with pore sizes ranging from 10 to 300 μm. The gradient scaffolds exhibited improved mechanical stability, with a compression resistance of 149 kPa, as opposed to the non-gradient scaffold's 116 kPa at 70 % strain, and a sustained degradation rate with only a 10 % loss of its initial weight within three weeks. Gradient scaffolds demonstrated a doubling of cell seeding efficiency to 47 % with dense and homogeneously distributed cellular layers, as evidenced by confocal and electron microscopy. Furthermore, the gradient scaffolds demonstrated superior osteodifferentiation, with significantly higher ALP and DMP1 production and enhanced extracellular matrix mineralization compared to gradientless macroporous scaffolds. This study provides insights into the design of macroporous scaffolds and emphasizes the advantages of pore gradient over homogeneous gradientless morphologies.

Magnetic biocomposite scaffold based on decellularized tendon ECM and MNP-deposited halloysite nanotubes: physicochemical, thermal, rheological, mechanical and in vitro biological evaluations

The development of new three-dimensional biomaterials with advanced versatile properties is critical to the success of tissue engineering (TE) applications. Here, (a) bioactive decellularized tendon extracellular matrix (dECM) with a sol-gel transition feature at physiological temperature, (b) halloysite nanotubes (HNT) with known mechanical properties and bioactivity, and (c) magnetic nanoparticles (MNP) with superparamagnetic and osteogenic properties were combined to develop a new scaffold that could be used in prospective bone TE applications. Deposition of MNPs on HNTs resulted in magnetic nanostructures without agglomeration of MNPs. A completely cell-free, collagen- and glycosaminoglycan- rich dECM was obtained and characterized. dECM-based scaffolds incorporated with 1%, 2% and 4% MNP-HNT were analysed for their physical, chemical, and in vitro biological properties. Fourier-transform infrared spectroscopy, x-ray powder diffractometry and vibrating sample magnetometry analyses confirmed the presence of dECM, HNT and MNP in all scaffold types. The capacity to form apatite layer upon incubation in simulated body fluid revealed that dECM-MNP-HNT is a bioactive material. Combining dECM with MNP-HNT improved the thermal stability and compressive strength of the macroporous scaffolds upto 2% MNP-HNT. In vitro cytotoxicity and hemolysis experiments showed that the scaffolds were essentially biocompatible. Human bone marrow mesenchymal stem cells adhered and proliferated well on the macroporous constructs containing 1% and 2% MNP-HNT; and remained metabolically active for at least 21 d in vitro. Collectively, the findings support the idea that magnetic nanocomposite dECM scaffolds containing MNP-HNT could be a potential template for TE applications.

Modification of Biodegradable Polymer Nanofibers for Cartilage Tissue Engineering Applications: A Review

Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physiochemical factors to improve or replace biological functions at the injured site. The designing of a biomaterial that can mimic the three-dimensional tissues in vivo is still challenging. Biodegradable polymers are used for the development of tissue engineering constructs in the form of sponges, films, and macroporous scaffolds, which do not influence cell fate processes such as cell differentiation, migration, and proliferation. Biodegradable polymer nanofibers fabricated by electrospinning have gathered great attention in tissue engineering applications. The electrospun materials have a nanofibrous morphology that is closest to the natural extracellular matrix (ECM). The electrospun material is composed of three-dimensional networks of nanosized fibrous materials that mimic an extracellular matrix such as collagen, elastin, and keratin. These polymers fabricated in the form of fibers in nanosize cause a more favorable microenvironment for cells. We prepared the PLGA/PPG (polylactic-co-glycolic acid/polypropylene glycol) nanofibers by electrospinning technique. PLGA (85:15)/PLGA (75:25) nanofibers are hydrophobic, which can be minimized by the addition of PPG to give better hydrophilicity for cell adhesion for tissue engineering constructs. The morphology of the electrospun fibers of the composite of PLGA and PPG was observed using scanning electron microscopy (SEM). The results proved that the small amount of polypropylene glycol polymer to the polylactic-co-glycolic acid (PLGA 85:15) drastically improves the hydrophilicity of the electrospun nanofibers. The addition of a small amount of hydrophilic polymer to the biodegradable hydrophobic polymer increases the hydrophilic property and can be used for nanofiber-based tissue engineering constructs. In addition, the biomimetic approach for tissue engineering scaffolds for cartilage repair has been discussed.

3D printed high-precision porous scaffolds prepared by fused deposition modeling induce macrophage polarization to promote bone regeneration

Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds’ physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds’ mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay for cytokine secretion levels. In vitro osteogenic capacity was determined through alkaline phosphatase and alizarin red staining. Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds’ immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells, exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization.

A biomaterial platform for T cell-specific gene delivery

Efficient T cell engineering is central to the success of CAR T cell therapy but involves multiple time-consuming manipulations, including T cell isolation, activation, and transduction. These steps add complexity and delay CAR T cell manufacturing, which takes a mean time of 4 weeks. To streamline T cell engineering, we strategically combine two critical engineering solutions - T cell-specific lentiviral vectors and macroporous scaffolds - that enable T cell activation and transduction in a simple, single step. The T cell-specific lentiviral vectors (referred to as STAT virus) target T cells through the display of an anti-CD3 antibody and the CD80 extracellular domain on their surface and provide robust T cell activation. Biocompatible macroporous scaffolds (referred to as Drydux) mediate robust transduction by providing effective interaction between naïve T cells and viral vectors. We show that when unstimulated peripheral blood mononuclear cells (PBMCs) are seeded together with STAT lentivirus on Drydux scaffolds, T cells are activated, selectively transduced, and reprogrammed in a single step. Further, we show that the Drydux platform seeded with PBMCs and STAT lentivirus generates tumor-specific functional CAR T cells. This potent combination of engineered lentivirus and biomaterial scaffold holds promise for an effective, simple, and safe avenue for in vitro and in vivo T cell engineering. Statement of significanceManufacturing T cell therapies involves lengthy and labor-intensive steps, including T cell selection, activation, and transduction. These steps add complexity to current CAR T cell manufacturing protocols and limit widespread patient access to this revolutionary therapy. In this work, we demonstrate the combination of engineered virus and biomaterial platform that, together, enables selective T cell activation and transduction in a single step, eliminating multistep T cell engineering protocols and significantly simplifying the manufacturing process.

Calcium crosslinked macroporous bacterial cellulose scaffolds with enhanced in situ mineralization and osteoinductivity for cranial bone regeneration

The inherent biological inertness and lack of three-dimensional (3D) macroporous structures greatly hinder the use of pristine bacterial cellulose (BC) as a tissue engineering scaffold for bone regeneration. To address this issue, we developed a simple and effective strategy to fabricate a BC-based scaffold with excellent bioactivity and macroporous structure by crosslinking short-cut BC nanofibers using Ca2+. The Ca2+ crosslinked macroporous BC scaffold (MPBC@Ca) presents better structural stability due to the enhanced cellulose hydration. Importantly, the Ca2+ on the surface of BC nanofibers can serve as an active nucleation site to accelerate the deposition of hydroxyapatite (HAp), which is beneficial for the construction of biomimetic bone tissue extracellular matrix (ECM) microenvironment. The HAp-deposited MPBC@Ca scaffolds (HAp-MPBC@Ca) with biomimetic ECM microenvironment have excellent cytocompatibility and enhanced osteogenic differentiation of stem cells in vitro. Furthermore, the results of in vivo tests revealed that the HAp-MPBC@Ca scaffold has favorable osteoinductivity and accelerates cranial bone tissue regeneration. This study proposes a novel strategy to improve the bioactivity of BC and presents the great potential of biomimetic ECM microenvironment BC-based scaffold for repairing large cranial bone defects.

Topographically and Chemically Enhanced Textile Polycaprolactone Scaffolds for Tendon and Ligament Tissue Engineering.

The use of tissue engineering to address the shortcomings of current procedures for tendons and ligaments is promising, but it requires a suitable scaffold that meets various mechanical, degradation-related, scalability-related, and biological requirements. Macroporous textile scaffolds made from appropriate fiber material have the potential to fulfill the first three requirements. This study aimed to investigate the biocompatibility, sterilizability, and functionalizability of a multilayer braided scaffold. These macroporous scaffolds with dimensions similar to those of the human anterior cruciate ligament consist of fibers with appropriate tensile strength and degradation behavior melt-spun from Polycaprolactone (PCL). Two different cross-sectional geometries resulting in significantly different specific surface areas and morphologies were used at the fiber level, and a Chitosan-graft-PCL (CS-g-PCL) surface modification was applied to the melt-spun substrates for the first time. All scaffolds elicited a positive cell response, and the CS-g-PCL modification provided a platform for incorporating functionalization agents such as drug delivery systems for growth factors, which were successfully released in therapeutically effective quantities. The fiber geometry was found to be a variable that could be manipulated to control the amount released. Therefore, scaled, surface-modified textile scaffolds are a versatile technology that can successfully address the complex requirements of tissue engineering for ligaments and tendons, as well as other structures.

Myeloid Cell-Triggered In Situ Cell Engineering for Robust Vaccine-Based Cancer Treatment.

Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e.g., tumor types, safety issues such as cytokine storms, and therapeutic benefits). Here, it is shown that an in situ injected macroporous myeloid cell adoptive scaffold (MAS) not only actively delivers antigens (Ags) that are triggered by scaffold-infiltrating cell surface thiol groups but also releases granulocyte-macrophage colony-stimulating factor and other adjuvant combos. Consequently, this promotes cell differentiation, activation, and migration from the produced monocyte and DC vaccines (MASVax) to stimulate antitumor T-cell immunity. Neoantigen-based MASVax combined with immune checkpoint blockade induces rejection of established tumors and long-term immune protection. The combined depletion of immunosuppressive myeloid cells further enhances the efficacy of MASVax, indicating the potential of myeloid cell-based therapies for immune enhancement and normalization treatment of cancer.

Biomimetic mineralization of platelet lysate/oxidized dextran cryogel as a macroporous 3D composite scaffold for bone repair

Scaffold development approaches using autologous sources for tissue repair are of great importance in obtaining bio-active/-compatible constructs. Platelet-rich plasma (PRP) containing various growth factors and platelet lysate (PL) derived from PRP are autologous products that have the potential to accelerate the tissue repair response by inducing a transient inflammatory event. Considering the regenerative capacity of PRP and PL, PRP/PL-based scaffolds are thought to hold great promise for tissue engineering as a natural source of autologous growth factors and a provider of mechanical support for cells. Here, a bio-mineralized PRP-based scaffold was developed using oxidized dextran (OD) and evaluated for future application in bone tissue engineering. Prepared PL/OD scaffolds were incubated in simulated body fluid (SBF) for 7, 14 and 21 d periods. Mineralized PL/OD scaffolds were characterized using Fourier transform infrared spectroscopy, x-ray diffraction spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis, porosity and compression tests. SEM and energy-dispersive x-ray spectroscopy analyses revealed mineral accumulation on the PL/OD scaffold as a result of SBF incubation. In vitro cytotoxicity and in vitro hemolysis tests revealed that the scaffolds were non-toxic and hemocompatible. Additionally, human osteoblasts (hOBs) exhibited good attachment and spreading behavior on the scaffolds and maintained their viability throughout the culture period. The alkaline phosphatase activity assay and calcium release results revealed that PL/OD scaffolds preserved the osteogenic properties of hOBs. Overall, findings suggest that mineralized PL/OD scaffold may be a promising scaffold for bone tissue engineering.

Enhanced antimicrobial properties and bioactivity of 3D-printed titanium scaffolds by multilayer bioceramic coating for large bone defects

The restoration of large bone defects caused by trauma, tumor resection, or infection is a major clinical problem in orthopedics and dentistry because postoperative infections, corrosion, and limited osteointegration of metal implants can lead to loosening of the implant. The aim of this study was to improve the surface properties of a 3D-printed (electron beam melting) Ti6Al4V-based macroporous scaffold by multilayer coating with bioactive silicate glasses (BAGs) and hydroxyapatite doped with a silver (AgHAP) or AgHAP additionally sonochemically modified with ZnO (ZnO-AgHAP). The coated scaffolds AgHAP_BAGs_Ti and ZnO-AgHAP_BAGs_Ti enhanced cytocompatibility in L929 and MRC5 cell lines and expressed bioactivity in simulated body fluid. A lower release of vanadium ions in coated samples compared to bare Ti scaffold indicates decreased dissolution of Ti alloy in coated samples. The coated samples reduced growth of Escherichia coli and Staphylococcus aureus for 4–6 orders of magnitude. Therefore, the 3D-printed Ti-based scaffolds coated with BAGs and (ZnO-)AgHAP have great potential for application as a multifunctional implant with antibacterial properties for the restoration of defects in load-bearing bones.

3D Printing of Bioactive Gel-like Double Emulsion into a Biocompatible Hierarchical Macroporous Self-Lubricating Scaffold for 3D Cell Culture.

The interconnected hierarchically porous structures are of key importance for potential applications as substrates for drug delivery, cell culture, and bioscaffolds, ensuring cell adhesion and sufficient diffusion of metabolites and nutrients. Here, encapsulation of a vitamin C-loaded gel-like double emulsion using a hydrophobic emulsifier and soy particles was performed to develop a bioactive bioink for 3D printing of highly porous scaffolds with enhanced cell biocompatibility. The produced double emulsions suggested a mechanical strength with the range of elastic moduli of soft tissues possessing a thixotropic feature and recoverable matrix. The outstanding flow behavior and viscoelasticity broaden the potential of gel-like double emulsion to engineer 3D scaffolds, in which 3D constructs showed a high level of porosity and excellent shape fidelity with antiwearing and self-lubricating properties. Investigation of cell viability and proliferation using fibroblasts (NIH-3T3) within vitamin C-loaded gel-like bioinks revealed that printed 3D scaffolds offered brilliant biocompatibility and cell adhesion. Compared to scaffolds without encapsulated vitamin C, 3D scaffolds containing vitamin C showed higher cell viability after 1 week of cell proliferation. This work represented a systematic investigation of hierarchical self-assembly in double emulsions and offered insights into mechanisms that control microstructure within supramolecular structures, which could be instructive for the design of advanced functional tissues.