Green conversion of waste alkaline battery material to zeolitic imidazolate framework-8 and its iodine capture mechanism.

Zeolitic imidazolate framework-8 (ZIF-8) exhibits excellent performance in capturing iodine. However, the solvent-based procedures and raw materials for ZIF-8 synthesis often lead to secondary pollution. We developed a solvent-minimizing method for preparing ZIF-8 via ball milling of raw material obtained from spent alkaline batteries, and studied its iodine-capture performance and structural changes. Exposure of the ZIF-8 to iodine vapor for 60 min demonstrated that it exhibited industrially competitive iodine-capture performance (the adsorbed amount reaches to 1123 mg g-1 within 60 min). Spectroscopic studies showed that ZIF-8 underwent a structural transformation upon iodine loading. Iodine molecules were adsorbed onto the surface of ZIF-8 and also formed C-I bond with the methyl groups on the imidazole rings, reducing iodine release. This work represents a comprehensive revelation of long-range order and short-range order evolution of ZIF-8 during iodine vapor adsorption over time. Moreover, this green synthesis of ZIF-8 is of lower cost and generates fewer harmful by-products than existing methods, and the produced ZIF-8 effectively entraps toxic iodine vapor. Thus, this synthesis enables a sustainable and circular material flow for beneficial utilization of waste materials.

Multilayered Shape-Morphing Scaffolds with a Hierarchical Structure for Uterine Tissue Regeneration.

Owing to dysfunction of the uterus, millions of couples around the world suffer from infertility. Different from conventional treatments, tissue engineering provides a new and promising approach to deal with difficult problems such as human tissue or organ failure. Adopting scaffold-based tissue engineering, three-dimensional (3D) porous scaffolds in combination with stem cells and appropriate biomolecules may be constructed for uterine tissue regeneration. In this study, a hierarchical tissue engineering scaffold, which mimicked the uterine tissue structure and functions, was designed, and the biomimicking scaffolds were then successfully fabricated using solvent casting, layer-by-layer assembly, and 3D bioprinting techniques. For the multilayered, hierarchical structured scaffolds, poly(l-lactide-co-trimethylene carbonate) (PLLA-co-TMC, "PLATMC" in short) and poly(lactic acid-co-glycolic acid) (PLGA) blends were first used to fabricate the shape-morphing layer of the scaffolds, which was to mimic the function of myometrium in uterine tissue. The PLATMC/PLGA polymer blend scaffolds were highly stretchable. Subsequently, after etching of the PLATMC/PLGA surface and employing estradiol (E2), polydopamine (PDA), and hyaluronic acid (HA), PDA@E2/HA multilayer films were formed on PLATMC/PLGA scaffolds to build an intelligent delivery platform to enable controlled and sustained release of E2. The PDA@E2/HA multilayer films also improved the biological performance of the scaffold. Finally, a layer of bone marrow-derived mesenchymal stem cell (BMSC)-laden hydrogel [which was a blend of gelatin methacryloyl (GelMA) and gelatin (Gel)] was 3D printed on the PDA@E2/HA multilayer films of the scaffold, thereby completing the construction of the hierarchical scaffold. BMSCs in the GelMA/Gel hydrogel layer exhibited excellent cell viability and could spread and be released eventually upon biodegradation of the GelMA/Gel hydrogel. It was shown that the hierarchically structured scaffolds could evolve from the initial flat shape into the tubular structure completely in an aqueous environment at 37 °C, fulfilling the requirement for curved scaffolds for uterine tissue engineering. The biomimicking scaffolds with a hierarchical structure and curved shape, high stretchability, and controlled and sustained E2 release appear to be very promising for uterine tissue regeneration.

Design and fabrication of biomimicking radially graded scaffolds via digital light processing 3D printing for bone regeneration.

Scaffolds are an essential component in bone tissue engineering (BTE). However, most of the current BTE scaffolds are homogeneous structures and do not resemble the graded architectures of native bone. In the current study, four types of biomimicking scaffold designs based on gyroid (G) and primitive (P) units with radially graded pore sizes were devised, and scaffolds of these designs with two porosity groups (65 vol% and 75 vol%) were fabricated via digital light processing (DLP) 3D printing using biphasic calcium phosphate (BCP). Scaffolds of the gyroid-gyroid (G-G) design displayed better dimensional accuracy, compressive property, and cell proliferation rate than gyroid-primitive (G-P), primitive-gyroid (P-G), and primitive-primitive (P-P) scaffolds. Subsequently, graded G-G scaffolds with different porosities were fabricated and the relationship between compressive strength and porosity was determined. Furthermore, the sintered BCP bioceramics fabricated via current manufacturing process exhibited excellent biocompatibility and bioactivity, indicating their high potential for BTE.

Structure and Properties of Gelatin Methacryloyl (GelMA) Synthesized in Different Reaction Systems.

Gelatin methacryloyl (GelMA) hydrogels have been extensively used for drug delivery and tissue engineering applications due to their good biocompatibility, biodegradability, and controllable photocurable efficiency. Phosphate buffer solution (PBS) is the most widely used reaction system for GelMA synthesis. However, carbonate-bicarbonate buffer solution (CBS) has been tried recently for synthesizing GelMA due to its high reaction efficiency. However, there is a lack of systematic investigation into possible differences in the structure and properties of GelMA synthesized in PBS and CBS, respectively. Therefore, in the current study, GelMA molecules with two degrees of methacryloylation (∼20 and ∼80%) were synthesized under PBS and CBS reaction systems, respectively, in comparable conditions. The results showed that because of the functionalization of methacrylate groups in gelatin chains, which could interfere with the intrachain and interchain interactions, such as hydrogen bonding, the GelMA molecules synthesized in PBS had distinct physical structures and exhibited different properties in comparison with those produced in CBS. GelMA hydrogels synthesized in PBS exhibited higher gel-sol transition temperatures and better photocurable efficiencies, mechanical strength, and biological properties. In contrast, GelMA hydrogels produced in CBS showed advantages in swelling performance and microstructures, such as pore sizes and porosities. In addition, GelMA synthesized in PBS and possessing a high degree of methacryloylation (the "GelMA-PH" polymer) showed great potential for three-dimensional (3D) bioprinting. This focused study has gained helpful new insights into GelMA and can provide guidance on the application of GelMA in 3D printing and tissue engineering.

A novel rapidly mineralized biphasic calcium phosphate with high acid-resistance stability for long-term treatment of dentin hypersensitivity.

OBJECTIVES: Treating dental hypersensitivity (DH) rapidly and maintaining long-term effectiveness remains challenging. We aimed to address this problem by fabricating a novel rapidly mineralized biphasic calcium phosphate (RMBCP), which could rapidly elicit mineralization to form hydroxyapatite (HA) and perform excellent acid-resistant stability, thus effectively blocking the exposed dental tubules and protecting them from acid attack. METHODS: RMBCP was firstly synthesized by precisely adjusting the molar ratio of acetic acid and calcium hydroxide and characterized by X-ray diffraction (XRD), X-ray fluorescence microprobe (XRF), Fourier-transform infrared (FTIR) spectrometer, scanning electron microscope (SEM), and transmission electron microscope (TEM). Subsequently, using a commercialized desensitizing agent, 45S5 bioglass (BG), as the control group, the mineralization performance of RMBCP was investigated in simulated body fluid (SBF), Dulbecco's modified eagle medium (DMEM), and even slightly acidic artificial saliva (pH=6.6). Moreover, the biocompatibility of RMBCP was studied. Finally, the tubule occlusion effect and acid-resistant stability of RMBCP were evaluated in vitro and in vivo. RESULTS: The rapid mineralization behavior of RMBCP could easily adhere to the dentin surface and block the dentinal tubules completely in vitro and in vivo within 7days. RMBCP performed high acid-resistant stability to maintain the long-term therapeutic effect of DH treatment. SIGNIFICANCE: Developing novel bioactive calcium phosphate materials with the ability to trigger mineralization for HA formation rapidly will be an effective strategy for the long-term treatment of dentin hypersensitivity.

Bioengineering Liver Organoids for Diseases Modelling and Transplantation.

Organoids as three-dimension (3D) cellular organizations partially mimic the physiological functions and micro-architecture of native tissues and organs, holding great potential for clinical applications. Advances in the identification of essential factors including physical cues and biochemical signals for controlling organoid development have contributed to the success of growing liver organoids from liver tissue and stem/progenitor cells. However, to recapitulate the physiological properties and the architecture of a native liver, one has to generate liver organoids that contain all the major liver cell types in correct proportions and relative 3D locations as found in a native liver. Recent advances in stem-cell-, biomaterial- and engineering-based approaches have been incorporated into conventional organoid culture methods to facilitate the development of a more sophisticated liver organoid culture resembling a near to native mini-liver in a dish. However, a comprehensive review on the recent advancement in the bioengineering liver organoid is still lacking. Here, we review the current liver organoid systems, focusing on the construction of the liver organoid system with various cell sources, the roles of growth factors for engineering liver organoids, as well as the recent advances in the bioengineering liver organoid disease models and their biomedical applications.

Low temperature hybrid 3D printing of hierarchically porous bone tissue engineering scaffolds within situdelivery of osteogenic peptide and mesenchymal stem cells.

Compared to other conventional scaffold fabrication techniques, three-dimensional (3D) printing is advantageous in producing bone tissue engineering scaffolds with customized shape, tailored pore size/porosity, required mechanical properties and even desirable biomolecule delivery capability. However, for scaffolds with a large volume, it is highly difficult to get seeded cells to migrate to the central region of the scaffolds, resulting in an inhomogeneous cell distribution and therefore lowering the bone forming ability. To overcome this major obstacle, in this study, cell-laden bone tissue engineering scaffolds consisting of osteogenic peptide (OP) loadedß-tricalcium phosphate (TCP)/poly(lactic-co-glycolic acid) (PLGA) (OP/TCP/PLGA, designated as OTP) nanocomposite struts and rat bone marrow derived mesenchymal stem cell (rBMSC)-laden gelatin/GelMA hydrogel rods were produced through 'dual-nozzle' low temperature hybrid 3D printing. The cell-laden scaffolds exhibited a bi-phasic structure and had a mechanical modulus of about 19.6 MPa, which was similar to that of human cancellous bone. OP can be released from the hybrid scaffolds in a sustained manner and achieved a cumulative release level of about 78% after 24 d. rBMSCs encapsulated in the hydrogel rods exhibited a cell viability of about 87.4% right after low temperature hybrid 3D printing and could be released from the hydrogel rods to achieve cell anchorage on the surface of adjacent OTP struts. The OP released from OTP struts enhanced rBMSCs proliferation. Compared to rBMSC-laden hybrid scaffolds without OP incorporation, the rBMSC-laden hybrid scaffolds incorporated with OP significantly up-regulated osteogenic differentiation of rBMSCs by showing a higher level of alkaline phosphatase expression and calcium deposition. This 'proof-of-concept' study has provided a facile method to form cell-laden bone tissue engineering scaffolds with not only required mechanical strength, biomimetic structure and sustained biomolecule release profile but also excellent cell delivery capability with uniform cell distribution, which can improve the bone forming ability in the body.

A facile way to construct Sr-doped apatite coating on the surface of 3D printed scaffolds to improve osteogenic effect.

Bone-like apatite coating fabricated by biomineralization process is a facile way for surface modification of porous scaffolds to improve interfacial behaviors and thus facilitate cell attachment, proliferation, and differentiation for bone tissue engineering. In this study, a Sr-containing calcium phosphate solution was made and used to construct a thick layer of Sr-doped bone-like apatite on the surface of 3D printed scaffolds via biomineralization process. Importantly, Sr-doped bone-like apatite could form and fully cover the 3D printed scaffolds surface in hours. The characterization results indicated that Sr2+ ions successfully replaced Ca2+ ions in bone-like apatite and the molar ratio of Sr/(Ca+Sr) was up to 8.2%. Furthermore, the Sr-doped apatite coating increased the compressive strength and Young's modulus of composite scaffolds. The compatibility and bioactivity of mineralized scaffolds were evaluated by cell attachment, proliferation, and differentiation of MC3T3-E1 cells. It was found that Sr-doped apatite coating could gradually release Sr2+ ions and further promote cell attachment, proliferation rate, and the expression of alkaline phosphatase activity and osteogenic related genes, such as collagen type I (Col I), Runt-related transcription factor 2 (Runx-2), osteopontin, and osterix. Therefore, the Sr-doped apatite coating fabricated by this facile and rapid biomineralization process offers a new strategy to modify 3D printed porous scaffolds with significantly improved mechanical and biological properties for bone tissue engineering applications.

Double-crosslinked bifunctional hydrogels with encapsulated anti-cancer drug for bone tumor cell ablation and bone tissue regeneration.

Many biomaterials are made and studied to provide anticancer therapy, and many other biomaterials have been developed to assist body tissue regeneration. It has been a challenge to design and produce effective multifunctional, or bifunctional, biomaterials for clinical applications to prevent cancer recurrence and, at the same time, to promote new tissue formation after surgical removal of the tumor for millions of cancer patients. In this study, bifunctional UV and Sr2+ double-crosslinked alginate (ALG)/allylated gelatin (GelAGE) hydrogels incorporated with polydopamine (PDA) particles were designed and made. Furthermore, doxorubicin hydrochloride (DOX), an anticancer drug, was incorporated in PDA particles. It was aimed for the new ALG/GelAGE-PDA@DOX hydrogels to exhibit anticancer synergy and hence provide combined chemotherapy and phototherapy (PTT) for bone tumor cell ablation. In vitro experiments using MG63 osteosarcoma cells showed that ALG/GelAGE-PDA@DOX hydrogels could effectively kill tumor cells through the synergy of controlled DOX release and hyperthermia ablation. It was also aimed for the new hydrogels to facilitate bone tissue regeneration at the original bone tumor site. The results of in vitro experiments demonstrated that owing to the release of Sr2+, the new hydrogels could promote the proliferation of rat bone mesenchymal stem cells (rBMSCs) and also the alkaline phosphatase (ALP) activity of cells, indicating their osteogenic promotion ability. The ALG/GelAGE-PDA@DOX hydrogels have therefore exhibited great potential for the treatment of bone tumor-related defects.

Nano-Hydroxyapatite Bone Scaffolds with Different Porous Structures Processed by Digital Light Processing 3D Printing.

The morphologies and structures of the scaffold have a significant influence on their mechanical and biological properties. In this work, different types of porous structures: Triply periodic minimal surface-Schwarz primitive (P), body-centered cubic, and cubic pore-shaped (CPS) hydroxyapatite scaffolds with ~70% porosity were fabricated through digital light processing (DLP) 3D printing technology. The compressive properties and in vitro cell evaluations such as cell proliferation and attachment morphology of these scaffolds were systematically compared. The results showed that the CPS scaffolds exhibited the highest compressive strength (~22.5 MPa) and modulus (~400 MPa). In addition, the CPS scaffolds also performed the most active cell metabolisms as compared to other two structures, which may account for the larger pore size and smaller curvature of the substrate. This study provides a general guidance for the fabrication and selection of porous bone scaffolds processed by DLP 3D printing.

Enhanced effect of nano-monetite hydrosol on dentin remineralization and tubule occlusion.

OBJECTIVES: We aim to investigate the dentin tubule occlusion and remineralization potential of a novel nano-monetite hydrosol (nMH). METHODS: First, nano-monetite hydrosol (nMH) was fabricated by homogeneous precipitation method. Then, the effectiveness of toothpaste with nMH on improving remineralization was evaluated by the measurement of tubule occluding ratio and acid-resistant stability compared with dentifrices comprising nano-hydroxyapatite hydrosol (nHH) and bioactive glass (BG). To explain this result, we studied the ions releasing and remineralization based on gelatin scaffold among nMH, nHH and BG. Finally, the cytotoxicity of these three minerals on Human dental pulp stem cells (HDPSCs) was evaluated. RESULTS: Processing for more than 7 days, the toothpaste containing nMH exhibited the significant remineralization potential and acid-resistant compared with two commercial de-sensitive dentifrices comprising nHH and BG. In addition, cytotoxicity test resulted that nMH has good cell compatibility to HDPSCs below extracts concentration of 3.12mg/mL. SIGNIFICANCE: Small size, the release of Ca2+ and PO43- with high concentration, strongly binding on dental surface, and fast transformation to HAp, were all needed in the preparation of effective dentin tubule occluding biomaterials.

Evaluation of BMP-2 and VEGF loaded 3D printed hydroxyapatite composite scaffolds with enhanced osteogenic capacity in vitro and in vivo.

Large-sized bone defect repair is a challenging task in orthopedic surgery. Porous scaffolds with controlled release of growth factors have been investigated for many years. In this study, a hydroxyapatite composite scaffold was prepared by 3D printing at low temperature and coating with layer-by-layer (LBL) assembly. Bone morphogenic protein-2 (BMP-2) and vascular endothelial growth factors (VEGF) were loaded into the composite scaffolds. The release of dual growth factors was analyzed in vitro. The cell growth and osteogenic differentiation were assessed by culturing MC3T3-E1 cells onto the scaffolds. In an established rabbit model of critical-sized calvarial defect (15 mm in diameter), the osteogenic and angiogenic properties after implantation of scaffolds were evaluated by micro-computed tomography (micro-CT) and stained sections. Our results showed that the scaffolds possessed well-designed porous structure and could release two growth factors in a sustained way. The micro-CT analysis showed that the scaffolds with BMP-2/VEGF could accelerate new bone formation. Findings of immunochemical staining of collagen type I and lectin indicated that better osteogenic and angiogenic properties induced by BMP-2 and VEGF. These results suggested that the novel composite scaffolds combined with BMP-2/VEGF had both osteogenic and angiogenic abilities which could enhance new bone formation with good quality. Thus, the combination of 3D printed scaffolds loaded with BMP-2/VEGF might provide a potential solution for bone repair and regeneration in clinical applications.

Biomimetic synthesis of Mg-substituted hydroxyapatite nanocomposites and three-dimensional printing of composite scaffolds for bone regeneration.

In this study, we have successfully fabricated magnesium (Mg) substituted hydroxyapatite nanocomposites (Mg-HA) by utilizing type I collagen (COL I) and citric acid (CA) through a bitemplate-induced biomimetic mineralization approach. The obtained composite nanoparticles were subsequently mixed with chitosan (CHI) and gelatin (Gel) to prepare porous scaffolds with interconnected structures by three-dimensional (3D) printing technique. The Mg-HA powders and composite scaffolds were characterized. The results showed that the substitution of Mg for Ca ions reduced the crystallinity of HA crystals, but did not significantly affect the size and structure of the nanocomposites. The morphology of Mg-HA scaffolds turned smoother compared with the HA scaffolds with Mg substitution. Furthermore, the biocompatibility of Mg-HA composite scaffolds was evaluated by metal ion release, cell attachment, proliferation, and differentiation of MC3T3-E1 cells. According to the results, as the more Ca2+ was substituted by Mg2+ , the more Mg2+ was released from the samples and the pH in cultured medium was more acidic. It was suggested that Mg-HA scaffolds presented higher cell attachment, proliferation rate, increased expression of alkaline phosphatase (ALP) activity and osteogenic related gene, including osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and COL I. Therefore, it was indicated that the 3D printed Mg-HA composite scaffolds with excellent biocompatibility and bioactivity were a potential candidate in bone tissue engineering.

Layer-by-layer coated porous 3D printed hydroxyapatite composite scaffolds for controlled drug delivery.

Interconnected porous scaffolds are widely used in the applications of tissue repair and regeneration. Sustained local delivery of drugs and growth factors around the implanted scaffolds could accelerate the growth of cells and contribute to the regeneration of damaged tissues. In this study, porous hydroxyapatite composite scaffolds were prepared through 3D bio-printing for bone tissue engineering and were subsequently coated with chitosan and sodium hyaluronate by layer-by-layer (LBL) deposition. It was found that the LBL coating on the porous scaffolds could reduce the swelling ratio of scaffolds in size and increase the compressive strength by about 70%. The degradation rate of the scaffolds slowed down due to the LBL coating. Rhodamine B (RHB) and bovine serum albumin (BSA) were chosen as model drugs in order to understand the loading and release behaviors of the scaffolds. Small RHB molecules could penetrate deep into the LBL coated scaffolds and released a little slower than that without coating. Meanwhile, large BSA molecules showed faster release rate compared to that without coating. In addition, there was no significant cytotoxicity effect of these composite scaffolds towards MC-3T3E1 cells and the scaffolds provided proper conditions for cell adhesion and proliferation, indicating that the printed hydroxyapatite composite scaffolds exhibit a great potential in hard tissue engineering as a sustained delivery system.

3D printing of strontium-doped hydroxyapatite based composite scaffolds for repairing critical-sized rabbit calvarial defects.

In this study, strontium substituted hydroxyapatite (Sr-HAP) was synthesized using collagen type I and citrate as bi-templates and the obtained nanoparticles with high similarity to natural bone minerals were made into composite scaffolds with interconnected porous structure using a three-dimensional (3D) printing technique. A calcium deficient structure of HAP phase was caused by doping Sr which was verified by Fourier transform infrared, x-ray diffractometer, scanning electron microscopy and transmission electron microscopy. The Sr/(Sr + Ca) molar ratio in Sr-HAP nanoparticles was 5.8% estimated by EDX. Furthermore, both 3D printed scaffolds made of Sr-HAP and HAP had uniform porous structure and porosity of about 60%. Cell culturing indicated that MC3T3-E1 cells could adhere on the surface of the scaffolds and the strontium substitution could enhance cell adhesion, proliferation and alkaline phosphatase activity. The printed composite scaffolds were used to repair critical-sized rabbit calvarial defects with a diameter of 15 mm. The results showed that the Sr-HAP scaffolds had better osteogenic capability and stimulated more new bone formation within 12 weeks. It was suggested that these printed Sr-HAP composite scaffolds possessed high potential as candidates in the application of bone augmentation and regeneration.