Gelatin/polyvinyl alcohol films loaded with doubly stabilized clove essential oil chitosomes: Preparation, characterization, and application in packing marinated steaks.

In this study, a promising active food-packaging film of Gelatin/polyvinyl alcohol (GEL/PVA) integrated with doubly stabilized clove essential oil chitosome nanoparticles (CNP) was developed to maintain the freshness of marinated steaks. Results from the XRD and SEM experiments indicated excellent compatibility between the CNP and GEL/PVA matrix. Additionally, CNP was found to introduce more free hydroxyl groups, enhance the water retention and surface wettability of the CNP-GEL/PVA (C-G/P) film, and significantly reduce the swelling index from 963.78% to 495.11% (p < 0.05). Notably, the highest tensile strength and elongation at break (53.745 MPa and 46.536%, respectively) were achieved with the addition of 30% (v/v, based on the volume of gelatin) CNP; UVC was fully absorbed with 40% CNP; and films containing 60% CNP showed optimal inhibition of both Staphylococcus aureus and Escherichia coil, extending the shelf life of marinated steak from 3 to 7 days.

Design of Collagen and Gelatin-based Electrospun Fibers for Biomedical Purposes: An Overview.

Collagen and gelatin are essential natural biopolymers commonly utilized in biomaterials and tissue engineering because of their excellent physicochemical and biocompatibility properties. They can be used either in combination with other biomacromolecules or particles or even exclusively for the enhancement of bone regeneration or for the development of biomimetic scaffolds. Collagen or gelatin derivatives can be transformed into nanofibrous materials with porous micro- or nanostructures and superior mechanical properties and biocompatibility using electrospinning technology. Specific attention was recently paid to electrospun mats of such biopolymers, due to their high ratio of surface area to volume, as well as their biocompatibility, biodegradability, and low immunogenicity. The fiber mats with submicro- and nanometer scale can replicate the extracellular matrix structure of human tissues and organs, making them highly suitable for use in tissue engineering due to their exceptional bioaffinity. The drawbacks may include rapid degradation and complete dissolution in aqueous media. The use of gelatin/collagen electrospun nanofibers in this form is thus greatly restricted for biomedicine. Therefore, the cross-linking of these fibers is necessary for controlling their aqueous solubility. This led to enhanced biological characteristics of the fibers, rendering them excellent options for various biomedical uses. The objective of this review is to highlight the key research related to the electrospinning of collagen and gelatin, as well as their applications in the biomedical field. The review features a detailed examination of the electrospinning fiber mats, showcasing their varying structures and performances resulting from diverse solvents, electrospinning processes, and cross-linking methods. Judiciously selected examples from literature will be presented to demonstrate major advantages of such biofibers. The current developments and difficulties in this area of research are also being addressed.

Impact of hydrophobic modification on biocompatibility of Alaska pollock gelatin microparticles.

This study investigates the impact of hydrophobic modification on the immunogenicity, cytotoxicity, and inflammatory response of Alaska pollock gelatin (ApGltn) microparticles (MPs). Gelatin, known for its inherent biocompatibility, was modified with decyl group (C10) to explore potential alterations in its interaction with the immune system. Immunogenicity was evaluated through the measurement of material-specific IgM and IgG responses, indicating no significant increase post-modification. Cytotoxicity against Caco-2 cell lines and NF-κB-mediated LPS-induced inflammation were also assessed, revealing no exacerbation by the modified MPs. Furthermore, C10 modification with different types of linkage such as secondary amine and amide structure did not influence immune reactivity. These findings suggest that C10 modification maintains the non-immunogenicity and biocompatibility of gelatin MPs, supporting their potential use in biomedical applications.

Comparing embolic particles for prostatic artery embolization to treat lower urinary tract symptoms in patients with benign prostatic hyperplasia.

PURPOSE: Compare the safety and efficacy of polyvinyl alcohol particles (PVA) versus trisacryl gelatin microspheres (Embospheres) versus hydrogel microspheres coated with polyzene-F (Embozenes) for prostatic artery embolization (PAE) to treat patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A single-center prospective cohort study from 2019 to 2023, including patients with international prostate symptom score (IPSS) ≥ 15 and/or quality of life score (QoL) ≥ 4. Allocation to embolic agents was performed chronologically: 100-300 µm PVA (n = 53), followed by 300-500 µm Embospheres (n = 50), and finally, 400 µm Embozenes (n = 50). All patients were evaluated at baseline and at 1 and 6 months after PAE with IPSS/QoL; peak urinary flow rate, post-void residual volume, and prostate volume with ultrasound and prostate-specific antigen. Adverse events and the need for prostatic re-interventions were assessed. RESULTS: There were no significant baseline differences between the three groups except for patient age (62.5 years PVA; 66.1 years Embospheres and 66.6 years Embozenes; p = 0.019). There were no major adverse events and no differences between groups regarding minor adverse events. All outcome measures improved significantly from baseline, with no significant differences between groups. Mean ± standard deviation IPSS/QoL improvement at 6 months: -10.7 ± 7.9/-2.2 ± 1.7 PVA; -10.4 ± 7.3/-2.0 ± 1.5 Embospheres; -10.4 ± 7.0/-2.2 ± 1.6 Embozenes (p = 0.987). Re-intervention rates after 6 months: 9% (n = 5/53) PVA; 14% (n = 7/50) Embospheres; 8% (n = 4/50) Embozenes (p = 0.591). CONCLUSIONS: PAE with PVA particles, Embospheres, and Embozenes is equally safe and effective in treating BPH-related lower urinary tract symptoms. CLINICAL RELEVANCE STATEMENT: This is the first prospective study showing equivalence between the most frequently used embolic agents for prostatic artery embolization. KEY POINTS: Different particles can be used interchangeably for prostatic artery embolization. The improvements in measured metrics were the same between groups, with no differences in adverse events. The need for prostatic medication and re-intervention rates were the same at 1 and 6 months after embolization.

(+)4-cholesten-3-one/sodium alginate/gelatin hydrogel for full-thickness wound repair and skin regeneration.

(+)4-cholesten-3-one has been proved to have potential wound healing effect in the process of wound regeneration. This study aimed to evaluate the effect of (+)4-cholesten-3-one/sodium alginate/gelatin on skin injury and reveal its potential molecular mechanism. First, we prepared sodium alginate/gelatin hydrogel (SA/Gel hydrogel) with different ratios and tested their characteristics. Based on these results, different concentrations of (+)4-cholesten-3-one were added into SA/Gel hydrogel. A full-thickness skin injury model was successfully established to evaluate wound healing activityin vivo. HE staining and Masson staining were used to evaluate the thickness of granulation tissue and collagen deposition level. Immunohistochemical staining and immunofluorescence staining were applied to detect the level of revascularization and proliferation in each group of wounds. Western blot, quantitative-PCR and immunofluorescence staining were used to detect the expression of proteins related to Wnt/ß-catenin signaling pathway in each group of wounds.In vitroresults showed that the hydrogel not only created a 3D structure for cell adhesion and growth, but also exhibited good swelling ability, excellent degradability and favorable bio-compatibility. Most importantly,in vivoexperiments further indicated that (+)4-cholesten-3-one/SA/Gel hydrogel effectively enhanced wound healing. The effectiveness is due to its superior abilities in accelerating healing process, granulation tissue regeneration, collagen deposition, promoting angiogenesis, tissue proliferation, as well as fibroblast activation and differentiation. The underlying mechanism was related to the Wnt/ß-catenin signaling pathway. This study highlighted that (+)4-cholesten-3-one/SA/Gel hydrogel holds promise as a wound healing dressing in future clinical applications.

Find alternative for bovine and porcine gelatin: Study on physicochemical, rheological properties and water-holding capacity of chicken lungs gelatin by ultrasound treatment.

In this study, the study on physicochemical, rheological properties and water-holding capacity of gelatin of chicken lungs was investigated to replace bovine and porcine gelatin. The extraction rates of chicken, bovine and porcine lung gelatin by ultrasound assisted alkaline protease were 52.12 %, 69.06 % and 70 %, respectively. Three lung gelatins had similar molecular weight distribution in SDS-PAGE with low content of high molecular weight subunits. The amino acid content of bovine lung gelatin (18.03 %) was higher than in chicken (16.62 %) and porcine lung (15.30 %). The highest intensity of 2θ = 7.5° diffraction peak in bovine lung gelatin was observed, which indicated that the triple helix content of bovine lung gelatin was higher than that of chicken and porcine lung gelatin. The lowest apparent viscosity of chicken lung gelatin was 0.253 mPa·s, but the highest water holding capacity of chicken lung gelatin was 331.72 %. Therefore, chicken lung gelatin can be used as a substitute for bovine and porcine gelatin in some functional properties.

Comparison of cation and anion-mediated resolution enhancement of bioprinted hydrogels for membranous tissue fabrication.

Fabrication of engineered thin membranous tissues (TMTs) presents a significant challenge to researchers, as these structures are small in scale, but present complex anatomies containing multiple stratified cell layers. While numerous methodologies exist to fabricate such tissues, many are limited by poor mechanical properties, need for post-fabrication, or lack of cytocompatibility. Extrusion bioprinting can address these issues, but lacks the resolution necessary to generate biomimetic, microscale TMT structures. Therefore, our goal was to develop a strategy that enhances bioprinting resolution below its traditional limit of 150 µm and delivers a viable cell population. We have generated a system to effectively shrink printed gels via electrostatic interactions between anionic and cationic polymers. Base hydrogels are composed of gelatin methacrylate type A (cationic), or B (anionic) treated with anionic alginate, and cationic poly-L-lysine, respectively. Through a complex coacervation-like mechanism, the charges attract, causing compaction of the base GelMA network, leading to reduced sample dimensions. In this work, we evaluate the role of both base hydrogel and shrinking polymer charge on effective print resolution and cell viability. The alginate anion-mediated system demonstrated the ability to reach bioprinting resolutions of 70 µm, while maintaining a viable cell population. To our knowledge, this is the first study that has produced such significant enhancement in extrusion bioprinting capabilities, while also remaining cytocompatible.

Methacrylated Wood Flour-Reinforced Gelatin-Based Gel Polymer as Green Electrolytes for Li-O2 Batteries.

With its very high theoretical energy density, the Li-O2 battery could be considered a valid candidate for future advanced energy storage solutions. However, the challenges hindering the practical application of this technology are many, as for example electrolyte degradation under the action of superoxide radicals produced upon cycling. In that frame, a gel polymer electrolyte was developed starting from waste-derived components: gelatin from cold water fish skin, waste from the fishing industry, and wood flour waste from the wood industry. Both were methacrylated and then easily cross-linked through a one-pot ultraviolet (UV)-initiated free radical polymerization, directly in the presence of the liquid electrolyte (0.5 M LiTFSI in DMSO). The wood flour works as cross-linking points, reinforcing the mechanical properties of the obtained gel polymer electrolyte, but it also increases Li-ion transport properties with an ionic conductivity of 3.3 mS cm-1 and a transference number of 0.65 at room temperature. The Li-O2 cells assembled with this green gel polymer electrolyte were able to perform 180 cycles at 0.1 mA cm-2, at a fixed capacity of 0.2 mAh cm-2, under a constant O2 flow. Cathodes post-mortem analysis confirmed that this electrolyte was able to slow down solvent degradation, but it also revealed that the higher reversibility of the cells could be explained by the formation of Li2O2 in the amorphous phase for a higher number of cycles compared to a purely gelatin-based electrolyte.

Preparation of Monodispersed Nanofibrous Gelatin Microspheres Using Homebuilt Microfluidics.

Gelatin, a protein derivative from collagen, is a versatile material with promising applications in tissue engineering. Among the various forms of gelatin scaffolds, nanofibrous gelatin microspheres (NFGMs) are attracting research efforts due to their fibrous nature and injectability. However, current methods for synthesizing nanofibrous gelatin microspheres (NFGMs) have limitations, such as wide size distributions and the use of toxic solvents. To address these challenges, the article introduces a novel approach. First, it describes the creation of a microfluidic device using readily available supplies. Subsequently, it outlines a unique process for producing monodispersed NFGMs through a combination of the microfluidic device and thermally induced phase separation (TIPS). This innovative method eliminates the need for sieving and the use of toxic solvents, making it a more ecofriendly and efficient alternative.

A novel biodegradable film based on chicken gelatin and κ-carrageenan cross-linked with oxidized phenolic compounds.

Natural and renewable polymers are gradually replacing petroleum-based plastics, mostly as a result of environmental concerns. Moreover, upcycling industrial food waste into new added-value products is a creative approach that is crucial for cleaner and more sustainable manufacturing. The aim of this study was to obtain an environmentally friendly biodegradable film using a combination of k-carrageenan (KCAR) and chicken gelatin (CGEL), which obtained from poultry by-products. The effects of varying concentrations of KCAR (0-2%) on the physical, permeability, textural, thermal, and microstructural properties of CGEL/KCAR composite films were evaluated. The findings demonstrated that an increase in KCAR enhanced the lightness and opacity levels of the films. Water vapor permeability (WVP) values reduced as the KCAR concentration increased. The lowest WVP value (0.0012 g.mm/h.m2.kpa) was seen in the treatment with 2% KCAR. Tensile strength (TS) values increased with increasing KCAR. The films' thermal stability was increased by the addition of KCAR. Microstructure assessments revealed a more compact and smooth structure in the KCAR-containing treatments, indicating improvements in WVP, thermal stability, and TS. Compared to the commercial cattle gelatin film, the CGEL film had higher TS and lower water solubility (WS). Overall, this study showed that the physical, mechanical, barrier and thermal and microstructural qualities of gelatin-based films may be enhanced by combining CGEL and KCAR to create an effective biodegradable film. Moreover, the comparison study between commercial cattle and chicken gelatin films revealed that cross-linked chicken gelatin films would be a suitable alternative for bovine gelatin films in the production of biodegradable film.

Improvement of jelly 3D printing using ultrasound treatment and calcium chloride.

This study investigated the effects of ultrasound treatment or calcium chloride (CaCl2) addition on the physical properties of jelly formulations. Elastic modulus (G'), loss modulus (G"), tan δ, shear modulus, yield stress (τ0), phase angle (δ), and gel strength were the parameters selected to describe the requirements of jelly printing, such as fidelity, shape retention, and extrudability. Ultrasound treatment of the jelly formulation without pectin increased the G' and shear moduli values, while decreasing the δ and gel strength. The addition of CaCl2 to the jelly formulation with pectin increased the G', G", shear modulus, τ0, and gel strength but lowered the tan δ and δ values. Both ultrasound treatment and CaCl2 addition improved the jelly printing requirements and demonstrated the potential to control the physical properties of jelly formulations for 3D printing using fused deposition modeling.

Wells syndrome following vaccination: A pediatric case with positive patch test to gelatin.

We report a 12-month-old boy with a skin eruption that developed 15 days after receiving the measles, mumps, rubella (MMR), pneumococcal, and meningococcal vaccines, consistent with the diagnosis of Wells syndrome. Patch testing showed a positive reaction to gelatin, which is used as a stabilizer for both live and inactivated vaccines. Gelatin was only present in the MMR vaccine.

Effect of viscosity of gelatin methacryloyl-based bioinks on bone cells.

The viscosity of gelatin methacryloyl (GelMA)-based bioinks generates shear stresses throughout the printing process that can affect cell integrity, reduce cell viability, cause morphological changes, and alter cell functionality. This study systematically investigated the impact of the viscosity of GelMA-gelatin bioinks on osteoblast-like cells in 2D and 3D culture conditions. Three bioinks with low, medium, and high viscosity prepared by supplementing a 5% GelMA solution with different concentrations of gelatin were evaluated. Cell responses were studied in a 2D environment after printing and incubation in non-cross-linked bioinks that caused the gelatin and GelMA to dissolve and release cells for attachment to tissue culture plates. The increased viscosity of the bioinks significantly affected cell area and aspect ratio. Cells printed using the bioink with medium viscosity exhibited greater metabolic activity and proliferation rate than those printed using the high viscosity bioink and even the unprinted control cells. Additionally, cells printed using the bioink with high viscosity demonstrated notably elevated expression levels of alkaline phosphatase (ALP) and bone morphogenetic protein-2 (BMP-2) genes. In the 3D condition, the printed cell-laden hydrogels were photo-cross-linked prior to incubation. The medium viscosity bioink supported greater cell proliferation compared to the high viscosity bioink. However, there were no significant differences in the expression of osteogenic markers between the medium and high viscosity bioinks. Therefore, the choice between medium and high viscosity bioinks should be based on the desired outcomes and objectives of the bone tissue engineering application. Furthermore, the bioprinting procedure with the medium viscosity bioink was used as an automated technique for efficiently seeding cells onto 3D printed porous titanium scaffolds for bone tissue engineering purposes.

GelMA loaded with platelet lysate promotes skin regeneration and angiogenesis in pressure ulcers by activating STAT3.

Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL's therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.

Materials based on biodegradable polymers chitosan/gelatin: a review of potential applications.

Increased mass manufacturing and the pervasive use of plastics in many facets of daily life have had detrimental effects on the environment. As a result, these worries heighten the possibility of climate change due to the carbon dioxide emissions from burning conventional, non-biodegradable polymers. Accordingly, biodegradable gelatin and chitosan polymers are being created as a sustainable substitute for non-biodegradable polymeric materials in various applications. Chitosan is the only naturally occurring cationic alkaline polysaccharide, a well-known edible polymer derived from chitin. The biological activities of chitosan, such as its antioxidant, anticancer, and antimicrobial qualities, have recently piqued the interest of researchers. Similarly, gelatin is a naturally occurring polymer derived from the hydrolytic breakdown of collagen protein and offers various medicinal advantages owing to its unique amino acid composition. In this review, we present an overview of recent studies focusing on applying chitosan and gelatin polymers in various fields. These include using gelatin and chitosan as food packaging, antioxidants and antimicrobial properties, properties encapsulating biologically active substances, tissue engineering, microencapsulation technology, water treatment, and drug delivery. This review emphasizes the significance of investigating sustainable options for non-biodegradable plastics. It showcases the diverse uses of gelatin and chitosan polymers in tackling environmental issues and driving progress across different industries.

Preparation and performance study of sodium alginate/bamboo fiber/gelatin ionic conductive self-healing hydrogel.

This study has been successfully developed the Sodium alginate/Bamboo fiber /Gelatin（SA/BF/Gel）composite conductive hydrogel with adhesive and self-healing properties. Through in-depth research, the influence of Gel content on the tensile, adhesive, self-healing properties, and conductivity of the SA/BF/Gel composite conductive hydrogel was discussed. The sensing performance and sensing mechanism of the material were also investigated, along with a preliminary exploration of its potential applications. An attempt was made to apply the SA/BF/Gel composite conductive hydrogel to 3D printing technology, establishing a connection between the rheological properties of the hydrogel and its printing structure. The addition of Gel significantly improved the flexibility of the hydrogel, with a conductivity of up to 3.12 S/m at a Gel content of 1.5 %. When employed as a sensor, the material exhibited high sensitivity (GF = 2.21) and excellent cyclic stability, rendering it suitable for a wide range of applications in real-time monitoring of bending movements of fingers and wrists, as well as dynamic contact and variations in contact forces on the hydrogel surface. The SA/BF/Gel composite conductive hydrogel has the potential to be utilized in a multitude of applications, including the development of smart wearable devices, the monitoring of individual human beings, and the integration of human beings and machines. Furthermore, the research findings associated with this hydrogel will provide a strong foundation for the advancement of materials science and the integration of smart technologies.

Valorisation of salmon backbones: Extraction of gelatine and its applicability in biodegradable films.

Salmon backbones make up about 10 % of the total fish weight and contain valuable proteins, collagen and lipids that can be used for marine ingredients production. Gelatine is derived from the collagen fraction and this study evaluated how different fractionation and extraction procedures can affect the yield and composition of extracted gelatine. Fractionation by mild thermal treatment of backbones (10 min in 40-42 °C) leads to structural changes of muscle, which improves separation of meat from bones and gives better yield of de-muscled backbone fractionation compared to mechanical meat removal. The highest yield of the gelatine (9.3 ± 0.3g dry gelatine from 100g de-muscled backbone dry material) was obtained from mechanically de-muscled backbones. De-muscled backbones were pre-treated with alkaline (0.04 N NaOH) followed by EDTA and 10 % ethanol for de-calcification and lipid extraction, respectively. Gelatine from pretreated backbones was extracted with 60 °C water. The amount of gelatine amino acids (sum of hydroxyproline, proline and glycine) was 43.4 ± 0.2 % of all amino acids in the gelatine. Extracted backbone gelatines showed film-forming ability. Gelatine films were obtained by casting procedure. Resulted salmon backbone 6 % gelatine and 30 % sorbitol films showed properties (e.g. water vapour permeability, colour difference, transparency value) similar to films obtained with commercial gelatine, indicating the capability of the extracted gelatines for its valorisation as edible coatings or bio-based film layers in packaging.

Characterization of gelatin-oxidized riclin cryogels and their applications as reusable ice cubes in shrimp preservation.

Traditional ice is usually employed to preserve food freshness and extend shelf life. However, ice cannot bear repeated freeze - thaw cycles during the transportation and retailing process, resulting in microbial cross-contamination and spoilage of foods. Herein, succinoglycan riclin was oxidated (RO) and crosslinked with gelatin (Ge), the Ge-RO cryogels were prepared via Schiff base reaction and three freeze - thaw cycles. The Ge-RO cryogels showed improved storage modulus (G') and thermal stability compared with pure gelatin hydrogel. The polymer framework of Ge-RO gels exhibited stable properties against ice crystals destructions during nine freeze - thaw treatments. During the storage and repeated freeze - thaw treatments of shrimps, Ge-RO cryogels exhibited a remarkable preservation effect on shrimps, and their freshness was evaluated using an electronic nose technique equipped with ten sensors. The results demonstrated that the shrimp muscle preserved in ice generated off-odors and resulted in high sensor responses. The sensor responses were reduced sharply of shrimps preserved in cryogels. Moreover, 1H NMR-based metabolomics analysis revealed that shrimps in Ge-RO cryogels group reversed the metabolic perturbations compared with the traditional ice group, the metabolic pathways were related to energy metabolism, nucleotide metabolism, and amino acid metabolism, which provide new clues to the freshness of shrimps. Furthermore, RO exhibited superior antimicrobial activity against E. coli and S. aureus microorganisms. Thus, the crosslinked cryogels are potentially applicable to food preservation, offering sustainable and reusable solutions against traditional ice.

Extracellular matrix regulation of cell spheroid invasion in a 3D bioprinted solid tumor-on-a-chip.

Tumor organoids and tumors-on-chips can be built by placing patient-derived cells within an engineered extracellular matrix (ECM) for personalized medicine. The engineered ECM influences the tumor response, and understanding the ECM-tumor relationship accelerates translating tumors-on-chips into drug discovery and development. In this work, we tuned the physical and structural characteristics of ECM in a 3D bioprinted soft-tissue sarcoma microtissue. We formed cell spheroids at a controlled size and encapsulated them into our gelatin methacryloyl (GelMA)-based bioink to make perfusable hydrogel-based microfluidic chips. We then demonstrated the scalability and customization flexibility of our hydrogel-based chip via engineering tools. A multiscale physical and structural data analysis suggested a relationship between cell invasion response and bioink characteristics. Tumor cell invasive behavior and focal adhesion properties were observed in response to varying polymer network densities of the GelMA-based bioink. Immunostaining assays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) helped assess the bioactivity of the microtissue and measure the cell invasion. The RT-qPCR data showed higher expressions of HIF-1α, CD44, and MMP2 genes in a lower polymer density, highlighting the correlation between bioink structural porosity, ECM stiffness, and tumor spheroid response. This work is the first step in modeling STS tumor invasiveness in hydrogel-based microfluidic chips. STATEMENT OF SIGNIFICANCE: We optimized an engineering protocol for making tumor spheroids at a controlled size, embedding spheroids into a gelatin-based matrix, and constructing a perfusable microfluidic device. A higher tumor invasion was observed in a low-stiffness matrix than a high-stiffness matrix. The physical characterizations revealed how the stiffness is controlled by the density of polymer chain networks and porosity. The biological assays revealed how the structural properties of the gelatin matrix and hypoxia in tumor progression impact cell invasion. This work can contribute to personalized medicine by making more effective, tailored cancer models.

Bone ingrowth induced by gelatin/chitosan internal matrix of 3DP Ti6Al4V scaffold.

Regarding its structural and mechanical adaptability to bone defects, 3D printed (3DP) Ti6Al4V scaffolds are widely used in orthopedics now, purposed to restore the function and mechanical stability of impaired bone. In scaffold fabrication, surface modification is acknowledged as a reliable strategy to enhance the interface interaction between 3DP Ti6Al4V scaffold and bone. Despite its advantage in bone-Ti6Al4V bonding improvement, surface modification lacks the ability to induce bone in-growth efficiently as expected. As an attempt to overcome this challenge, in the current work the inner voids of 3DP Ti6Al4V scaffold were occupied by a gelatin/chitosan porous matrix, purposed to act as a platform for guiding bone ingrowth. Firstly, the gelatin/chitosan matrix was prepared via freeze-drying using genipin as a crosslinker, resulting in a trabecular bone-like interconnected porous network characterized with a gelatin/chitosan ratio dependent swelling capability, degradation and model anti-bacterial drug release behavior. Besides of that, gelatin in the matrix was witnessed to accelerate biomineralization in simulated body fluid. Secondly, a formulated gelatin/chitosan matrix was embedded into 3DP Ti6Al4V scaffold to generate a composite scaffold capable of inducing bone in-growth. The followed studies showed gelatin/chitosan matrix can endow the scaffold with good biological and sustained drug release properties, along with minimal change to the compressive strength of the scaffold. The in vivo experiment results revealed that after 4 weeks of implantation, more new bone formation was witnessed in the inner structure of the composite scaffold than the 3DP Ti6Al4V scaffold, with the average bone volume fraction (BV/TV) value increased from 24.09 % to 46.08 %, the average trabecular bone thickness (Tb. Th) value increased from 0.118 mm to 0.278 mm. Therefore, it was confirmed an inner matrix in 3DP Ti6Al4V scaffold played an essential role in guiding bone in-growth.