A Hierarchical Hydrogel Impregnation Strategy Enables Brittle-Failure-Free 3D-Printed Bioceramic Scaffolds.

3D-printed bioceramic scaffolds offer great potential for bone tissue engineering (BTE) but their inherent brittleness and reduced mechanical properties at high porosities can easily result in catastrophic fractures. Herein, this study presents a hierarchical hydrogel impregnation strategy, incorporating poly(vinyl alcohol) (PVA) hydrogel into the macro- and micropores of bioceramic scaffolds and synergistically reinforcing it via freeze-casting assisted solution substitution (FASS) in a tannic acid (TA)-glycerol solution. By effectively mitigating catastrophic brittle failures, the hydrogel-impregnated scaffolds showcase three- and 100-fold enhancement in mechanical energy absorption under compression (5.05 MJ m-3) and three-point bending (3.82 MJ m-3), respectively. The reinforcement mechanisms are further investigated by experimental and simulation analyses, revealing a multi-scale synergy of fracture and fragmentation resistance through macro and micro-scale fiber bridging, and nano and molecular-scale hydrogel reinforcement. Also, the scaffolds acquire additional antibacterial and drug-loading capabilities from the hydrogel phase while maintaining favorable cell biocompatibility. Therefore, this study demonstrates a facile yet effective approach for preparing brittle-failure-free bioceramic scaffolds with enhanced biological functionalities, showcasing immense potential for BTE applications.

3D printable strong and tough composite organo-hydrogels inspired by natural hierarchical composite design principles.

Fabrication of composite hydrogels can effectively enhance the mechanical and functional properties of conventional hydrogels. While ceramic reinforcement is common in many hard biological tissues, ceramic-reinforced hydrogels lack a similar natural prototype for bioinspiration. This raises a key question: How can we still attain bioinspired mechanical mechanisms in composite hydrogels without mimicking a specific composition and structure? Abstracting the hierarchical composite design principles of natural materials, this study proposes a hierarchical fabrication strategy for ceramic-reinforced organo-hydrogels, featuring (1) aligned ceramic platelets through direct-ink-write printing, (2) poly(vinyl alcohol) organo-hydrogel matrix reinforced by solution substitution, and (3) silane-treated platelet-matrix interfaces. Unit filaments are further printed into a selection of bioinspired macro-architectures, leading to high stiffness, strength, and toughness (fracture energy up to 31.1 kJ/m2), achieved through synergistic multi-scale energy dissipation. The materials also exhibit wide operation tolerance and electrical conductivity for flexible electronics in mechanically demanding conditions. Hence, this study demonstrates a model strategy that extends the fundamental design principles of natural materials to fabricate composite hydrogels with synergistic mechanical and functional enhancement.

A Universal Chelation-Induced Selective Demetallization Strategy for Bioceramic Nanosheets (BCene).

The emergence of nanosheet materials like graphene and phosphorene, which are created by breaking the interlayer van der Waals force, has revolutionized multiple fields. Layered inorganic materials are ubiquitous in materials like bioceramics, semiconductors, superconductors, etc. However, the strong interlayer covalent or ionic bonding in these crystals makes it difficult to fabricate nanosheets from them. In this study, we present a simple technique to produce nanosheets from layered crystals by selectively exfoliating their interlayer metal atoms using the metal-chelation reaction. As a proof of concept, we successfully produced bioceramic nanosheets (BCene) by extracting Ca layers from Akermanite (AKT). The 3D-printed BCene scaffolds exhibited superior mechanical strength and in vitro bioactivity compared to the scaffolds made from AKT nanopowders. Our findings demonstrate the outstanding potential of BCene nanosheets in tissue engineering. Additionally, the selective demetallization technique for nanosheet production could be applied to other inorganic layered crystals to optimize their performance.

Prestrain Programmable 4D Printing of Nanoceramic Composites with Bioinspired Microstructure.

Four-dimensional (4D) printing enables programmable, predictable, and precise shape change of responsive materials to achieve desirable behaviors beyond conventional three-dimensional (3D) printing. However, applying 4D printing to ceramics remains challenging due to their intrinsic brittleness and inadequate stimuli-responsive ability. Here, this work proposes a conceptional combination of bioinspired microstructure design and a programmable prestrain approach for 4D printing of nanoceramics. To overcome the flexibility limitation, the bioinspired concentric cylinder structure in the struts of 3D printed lattices are replicated to develop origami nanoceramic composites with high inorganic content (95 wt%). Furthermore, 4D printing is achieved by applying a programmed prestrain to the printed lattices, enabling the desired deformation when the prestrain is released. Due to the bioinspired concentric cylinder microstructures, the printed flexible nanoceramic composites exhibit superior mechanical performance and anisotropic thermal management capability. Further, by introducing oxygen vacancies to the ceramic nanosheets, conductive nanoceramic composites are prepared with a unique sensing capability for various sensing applications. Hence, this research breaks through the limitation of ceramics in 4D printing and achieves high-performance shape morphing materials for applications under extreme conditions, such as space exploration and high-temperature systems.

Hierarchical Porous Ceramics with Distinctive Microstructures by Emulsion-Based Direct Ink Writing.

Hierarchical porous materials are ubiquitous in nature and have inspired the fabrication of cellular structures for a multitude of applications. As an extrusion-based 3D printing technique, direct ink writing (DIW) allows for customizable design and accurate control of printed structures. Recently, its combination with colloidal processing methods used for bulk porous ceramics, such as emulsion templating, has further extended its capability of fabricating porous ceramics across multiple length scales. In light of the recent development, the ink formulation for emulsion-based DIW can be further explored, and there is still a need for a better understanding of the structure-property relationship. Herein, we introduce two types of gelling additives, i.e., poly(ethylenimine) (PEI) and Pluronic F-127, respectively, into particle-stabilized emulsions and fabricate hierarchical porous alumina lattices by DIW. We discover that the two gelling additives can lead to distinctive microstructures due to their different gelling mechanisms. Moreover, the 3D printed hierarchical porous ceramic lattices are found to exhibit a potential energy absorption property. The effects of ink formulations, including gelling additives and solid loading, on ink rheology, microstructure, and mechanical properties are investigated. The 3D printed hierarchical porous ceramic lattices exhibit a high average porosity of 73.7%-79.3% with an average compressive strength of 1.53-9.61 MPa and a specific energy absorption of 0.33-2.67 J/g. Featuring two distinctive microstructures with tunable structural features and mechanical properties, the 3D printed hierarchical porous ceramics in this study have potential in many applications, including lightweight structures, tissue engineering scaffolds, filtration, etc.

Toward stronger robocast calcium phosphate scaffolds for bone tissue engineering: A mini-review and meta-analysis.

Among different treatments of critical-sized bone defects, bone tissue engineering (BTE) is a fast-developing strategy centering around the fabrication of scaffolds that can stimulate tissue regeneration and provide mechanical support at the same time. This area has seen an extensive application of bioceramics, such as calcium phosphate, for their bioactivity and resemblance to the composition of natural bones. Moreover, recent advances in additive manufacturing (AM) have unleashed enormous potential in the fabrication of BTE scaffolds with tailored porous structures as well as desired biological and mechanical properties. Robocasting is an AM technique that has been widely applied to fabricate calcium phosphate scaffolds, but most of these scaffolds do not meet the mechanical requirements for load-bearing BTE scaffolds. In light of this challenge, various approaches have been utilized to mechanically strengthen the scaffolds. In this review, the current state of knowledge and existing research on robocasting of calcium phosphate scaffolds are presented. Applying the Gibson-Ashby model, this review provides a meta-analysis from the published literature of the compressive strength of robocast calcium phosphate scaffolds. Furthermore, this review evaluates different approaches to the mechanical strengthening of robocast calcium phosphate scaffolds. The aim of this review is to provide insightful data and analysis for future research on mechanical strengthening of robocast calcium phosphate scaffolds and ultimately for their clinical applications.

Downregulation of CPE regulates cell proliferation and chemosensitivity in pancreatic cancer.

Pancreatic cancer (PC) is one of the most common cancers worldwide and a leading cause of cancer-related death. Discovering novel targets is a key for its therapy. Carboxypeptidase E (CPE), a subtype of the pro-protein convertases, has been shown to be upregulated in many types of cancer, yet its function in PC remains elusive. The expressions of CPE in PC cell lines and cancer patients were investigated by Western blot and qRT-PCR. In PC cell line BX-pc-3, CPE was downregulated and its effect on cancer cell proliferation, migration, cisplatin chemosensitivity, and in vivo tumor growth was analyzed by Western blot, proliferation assay, invasion assay, and in vivo transplantation, respectively. The expression of nuclear factor-kappaB (NF-κB), a possible downstream target of CPE was examined by Western blot upon CPE regulation in PC cells, and the effects of inhibiting NF-κB on PC cell invasion and proliferation were examined. CPE was significantly upregulated in PC cell lines and tumor tissues. Proliferation and invasion assays indicated that downregulation of CPE inhibited cancer cell growth and migration and increased chemosensitivity to cisplatin. Inoculation of small interfering RNA (siRNA) transfected BX-pc-3 cells into null mice demonstrated that downregulation of CPE prevented tumor growth in vivo. NF-κB was directly regulated by CPE in pancreatic cancer, and siRNA-mediated inhibition of NF-κB exerted similar anti-tumor effect as downregulating CPE. Taken together, our results demonstrate that CPE plays an important role in pancreatic cancer. Inhibition of CPE may serve as a potential target for PC therapeutics.