Microfluidics-assisted fabrication of natural killer cell-laden microgel enhances the therapeutic efficacy for tumor immunotherapy.

Recently, interest in cancer immunotherapy has increased over traditional anti-cancer therapies such as chemotherapy or targeted therapy. Natural killer (NK) cells are part of the immune cell family and essential to tumor immunotherapy as they detect and kill cancer cells. However, the disadvantage of NK cells is that cell culture is difficult. In this study, porous microgels have been fabricated using microfluidic channels to effectively culture NK cells. Microgel fabrication using microfluidics can be mass-produced in a short time and can be made in a uniform size. Microgels consist of photo cross-linkable polymers such as methacrylic gelatin (GelMa) and can be regulated via controlled GelMa concentrations. NK92 cell-laden three-dimensional (3D) microgels increase mRNA expression levels, NK92 cell proliferation, cytokine release, and anti-tumor efficacy, compared with two-dimensional (2D) cultures. In addition, the study confirms that 3D-cultured NK92 cells enhance anti-tumor effects compared with enhancement by 2D-cultured NK92 cells in the K562 leukemia mouse model. Microgels containing healthy NK cells are designed to completely degrade after 5 days allowing NK cells to be released to achieve cell-to-cell interaction with cancer cells. Overall, this microgel system provides a new cell culture platform for the effective culturing of NK cells and a new strategy for developing immune cell therapy.

3D-printed versatile biliary stents with nanoengineered surface for anti-hyperplasia and antibiofilm formation.

Biliary strictures are characterized by the narrowing of the bile duct lumen, usually caused by surgical biliary injury, cancer, inflammation, and scarring from gallstones. Endoscopic stent placement is a well-established method for the management of biliary strictures. However, maintaining optimal mechanical properties of stents and designing surfaces that can prevent stent-induced tissue hyperplasia and biofilm formation are challenges in the fabrication of biodegradable biliary stents (BBSs) for customized treatment. This study proposes a novel approach to fabricating functionalized polymer BBSs with nanoengineered surfaces using 3D printing. The 3D printed stents, fabricated from bioactive silica poly(ε-carprolactone) (PCL) via a sol-gel method, exhibited tunable mechanical properties suitable for supporting the bile duct while ensuring biocompatibility. Furthermore, a nanoengineered surface layer was successfully created on a sirolimus (SRL)-coated functionalized PCL (fPCL) stent using Zn ion sputtering-based plasma immersion ion implantation (S-PIII) treatment to enhance the performance of the stent. The nanoengineered surface of the SRL-coated fPCL stent effectively reduced bacterial responses and remarkably inhibited fibroblast proliferation and initial burst release of SRL in vitro systems. The physicochemical properties and biological behaviors, including in vitro biocompatibility and in vivo therapeutic efficacy in the rabbit bile duct, of the Zn-SRL@fPCL stent demonstrated its potential as a versatile platform for clinical applications in bile duct tissue engineering.

Longitudinal long term follow up investigation on the carcinogenic impact of polyhexamethylene guanidine phosphate in rat models.

Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar-alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar-alveolar hyperplasia progression, although bronchiolar-alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.

Decellularized matrix bioink with gelatin methacrylate for simultaneous improvements in printability and biofunctionality.

Gelatin methacrylate (GelMA) bioink has been widely used in bioprinting because it is a printable and biocompatible biomaterial. However, it is difficult to print GelMA bioink without any temperature control because it has a thermally-sensitive rheological property. Therefore, in this study, we developed a temperature-controlled printing system in real time without affecting the viability of the cells encapsulated in the bioink. In addition, a skin-derived decellularized extracellular matrix (SdECM) was printed with GelMA to better mimic the native tissue environment compared with solely using GelMA bioink with the enhancement of structural stability. The temperature setting accuracy was calculated to be 98.58 ± 1.8 % for the module and 99.48 ± 1.33 % for the plate from 5 °C to 37 °C. The group of the temperature of the module at 10 °C and the plate at 20 °C have 93.84 % cell viability with the printable range in the printability window. In particular, the cell viability and proliferation were increased in the encapsulated fibroblasts in the GelMA/SdECM bioink, relative to the GelMA bioink, with a morphology that significantly spread for seven days. The gene expression and growth factors related to skin tissue regeneration were relatively upregulated with SdECM components. In the bioprinting process, the rheological properties of the GelMA/SdECM bioink were successfully adjusted in real time to increase printability, and the native skin tissue mimicked components providing tissue-specific biofunctions to the encapsulated cells. The developed bioprinting strategies and bioinks could support future studies related to the skin tissue reconstruction, regeneration, and other medical applications using the bioprinting process.

BMP-2-immobilized PCL 3D printing scaffold with a leaf-stacked structure as a physically and biologically activated bone graft.

Although three-dimensional (3D) printing techniques are used to mimic macro- and micro-structures as well as multi-structural human tissues in tissue engineering, efficient target tissue regeneration requires bioactive 3D printing scaffolds. In this study, we developed a bone morphogenetic protein-2 (BMP-2)-immobilized polycaprolactone (PCL) 3D printing scaffold with leaf-stacked structure (LSS) (3D-PLSS-BMP) as a bioactive patient-tailored bone graft. The unique LSS was introduced on the strand surface of the scaffold via heating/cooling in tetraglycol without significant deterioration in physical properties. The BMP-2 adsorbed on3D-PLSS-BMPwas continuously released from LSS over a period of 32 d. The LSS can be a microtopographical cue for improved focal cell adhesion, proliferation, and osteogenic differentiation.In vitrocell culture andin vivoanimal studies demonstrated the biological (bioactive BMP-2) and physical (microrough structure) mechanisms of3D-PLSS-BMPfor accelerated bone regeneration. Thus, bioactive molecule-immobilized 3D printing scaffold with LSS represents a promising physically and biologically activated bone graft as well as an advanced tool for widespread application in clinical and research fields.

Hyaluronic acid/polyphenol sunscreens with broad-spectrum UV protection properties from tannic acid and quercetin.

Currently, commercial sunscreens cause a number of biotoxicity and environmental issues, making it imperative to develop biocompatible alternatives. In this study, we aimed to develop an alternative sunscreen from two ecofriendly and biocompatible natural polyphenolic compounds, tannic acid (TA) and quercetin (Que). The sunscreen was prepared through a simple process using an oil-in-water emulsion as the medium and hyaluronic acid (HA) as the base polymer to improve biocompatibility. The HA/TA/Que. sunscreen prepared in this study exhibits 0 % transmittance in the UVB region and <15 % transmittance in the UVA region, resulting in excellent sun-protection properties (SPF 30). Remarkably, the as-prepared HA/TA/Que. sunscreen has a suitable viscosity and similar UV protection properties to those of commercial sunscreens. The HA/TA/Que. sunscreen also exhibits 90.4 % antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl, demonstrating an ability to effectively capture reactive oxygen species that directly affect the skin. In addition, the cell viability was >90 % at a concentration of 50 µg/mL after 7 days, indicating excellent cytocompatibility. Owing to its various advantageous features, the HA/TA/Que. sunscreen with excellent sun protection properties and multiple functionalities is expected to resolve many environmental and biological issues caused by commercial sunscreens.

Correction: A wearable colorimetric sweat pH sensor-based smart textile for health state diagnosis.

Correction for 'A wearable colorimetric sweat pH sensor-based smart textile for health state diagnosis' by Ji-Hwan Ha et al., Mater. Horiz., 2023, 10, 4163-4171, https://doi.org/10.1039/d3mh00340j.

Peptide derived from stromal cell-derived factor 1δ enhances the in vitro expression of osteogenic proteins via bone marrow stromal cell differentiation and promotes bone formation in in vivo models.

Mesenchymal stem cells (MSCs) rely on chemokines and chemokine receptors to execute their biological and physiological functions. Stromal cell-derived factor-1 (SDF-1) is upregulated in injury sites, where it acts as a chemotactic agent, attracting CXCR4-expressing MSCs, which play a pivotal role in the healing and regeneration of tissue throughout the body. Furthermore, SDF-1 expression has been observed in regions experiencing inflammation-induced bone destruction and fracture sites. In this study, we identified a novel peptide called bone-forming peptide-5 (BFP-5), derived from SDF-1δ, which can promote the osteogenesis of MSCs as well as bone formation and healing. Multipotent bone marrow stromal cells treated with BFP-5 showed enhanced alizarin red S staining and higher alkaline phosphatase (ALP) activity. Moreover, ALP and osterix proteins were more abundantly expressed when cells were treated with BFP-5 than SDF-1α. Histology and microcomputed tomography data at 12 weeks demonstrated that both rabbit and goat models transplanted with polycaprolactone (PCL) scaffolds coated with BFP-5 showed significantly greater bone formation than animals transplanted with PCL scaffolds alone. These findings suggest that BFP-5 could be useful in the development of related therapies for conditions associated with bones.

A bioactive microparticle-loaded osteogenically enhanced bioprinted scaffold that permits sustained release of BMP-2.

Extrusion-based bioprinting technology is widely used for tissue regeneration and reconstruction. However, the method that uses only hydrogel as the bioink base material exhibits limited biofunctional properties and needs improvement to achieve the desired tissue regeneration. In this study, we present a three-dimensionally printed bioactive microparticle-loaded scaffold for use in bone regeneration applications. The unique structure of the microparticles provided sustained release of growth factor for > 4 weeks without the use of toxic or harmful substances. Before and after printing, the optimal particle ratio in the bioink for cell viability demonstrated a survival rate of ≥ 85% over 7 days. Notably, osteogenic differentiation and mineralization-mediated by human periosteum-derived cells in scaffolds with bioactive microparticles-increased over a 2-week interval. Here, we present an alternative bioprinting strategy that uses the sustained release of bioactive microparticles to improve biofunctional properties in a manner that is acceptable for clinical bone regeneration applications.

A wearable colorimetric sweat pH sensor-based smart textile for health state diagnosis.

Sweat pH is an important indicator for diagnosing disease states, such as cystic fibrosis. However, conventional pH sensors are composed of large brittle mechanical parts and need additional instruments to read signals. These pH sensors have limitations for practical wearable applications. In this study, we propose wearable colorimetric sweat pH sensors based on curcumin and thermoplastic-polyurethane (C-TPU) electrospun-fibers to diagnose disease states by sweat pH monitoring. This sensor aids in pH monitoring by changing color in response to chemical structure variation from enol to di-keto form via H-atom separation. Its chemical structure variation changes the visible color due to light absorbance and reflectance changes. Furthermore, it can rapidly and sensitively detect sweat pH due to its superior permeability and wettability. By O2 plasma activation and thermal pressing, this colorimetric pH sensor can be easily attached to various fabric substrates such as swaddling and patient clothing via surface modification and mechanical interlocking of C-TPU. Furthermore, the diagnosable clothing is durable and reusable enough to neutral washing conditions due to the reversible pH colorimetric sensing performance by restoring the enol form of curcumin. This study contributes to the development of smart diagnostic clothing for cystic fibrosis patients who require continuous sweat pH monitoring.

NK cells encapsulated in micro/macropore-forming hydrogels via 3D bioprinting for tumor immunotherapy.

BACKGROUND: Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results. METHOD: To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels. RESULTS: It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model. CONCLUSION: We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro-macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.

Assessment of Esophageal Reconstruction via Bioreactor Cultivation of a Synthetic Scaffold in a Canine Model.

OBJECTIVES: Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. METHODS: We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. RESULTS: Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. CONCLUSION: Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

Highly gallol-substituted, rapidly self-crosslinkable, and robust chitosan hydrogel for 3D bioprinting.

Although three-dimensional (3D) bioprinting is a promising technology for reconstructing artificial tissues and organs using bioink, there is a lack of a bioink that satisfies all requirements, including printability, gelation, mechanical properties, and cytocompatibility, Herein, a novel self-crosslinkable bioink derived from chitosan (CS) and gallic acid (GA) is presented. 3D printed scaffolds with excellent shape fidelity are realized by systematically analyzing the self-crosslinking mechanism of hydrogel formation from CS-GA conjugates and by optimizing various parameters of the printing process. The CS-GA hydrogel forms rapidly in a physiological pH without any chemical crosslinking agent. In addition, the CS-GA hydrogel exhibited various physical and chemical intermolecular interactions, fast gelation rates, and excellent mechanical properties (>337 kPa). Moreover, the CS-GA hydrogel singificantly improves the cell viability (>92 %) and proliferation of the bioink. Therefore, the self-crosslinkable CS-GA bioink has great potential to overcome the limitations of conventional bioinks.

Three-dimensional bioprinting of mesenchymal stem cells using an osteoinductive bioink containing alginate and BMP-2-loaded PLGA nanoparticles for bone tissue engineering.

Hydrogels mimicking the physicochemical properties of the native extracellular matrix have attracted great attention as bioinks for three-dimensional (3D) bioprinting in tissue engineering applications. Alginate is a widely used bioink with beneficial properties of fast gelation and biocompatibility; however, bioprinting using alginate-based bioinks has several limitations, such as poor printability, structural instability, and limited biological activities. To address these issues, we formulated various bioinks using bone morphogenetic protein-2 (BMP-2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and alginate for mesenchymal stem cell (MSC) printing and induction of osteogenic differentiation. Incorporation of PLGA nanoparticles into alginate could enhance the mechanical properties and printability of the bioink. In particular, Alg/NPN30 (30 mg/mL PLGA nanoparticles and 3% w/v alginate) was most suitable for 3D printing with respect to printability and stability. BMP-2-loaded PLGA nanoparticles (NPBMP-2) displayed sustained in vitro release of BMP-2 for up to two weeks. Further in vitro studies indicated that bioinks composed of alginate and NPBMP-2 significantly induced osteogenesis of the MSCs compared with other controls, evidenced by enhanced calcium deposition, alkaline phosphatase activity, and gene expression of osteogenic markers. Our novel bioink consisting of widely used biocompatible components displays good printability, stability, and osteogenic inductivity, and holds strong potential for cell printing and bone tissue engineering applications.

An osteogenic bioink composed of alginate, cellulose nanofibrils, and polydopamine nanoparticles for 3D bioprinting and bone tissue engineering.

Bioprinting is an emerging technology for manufacturing cell-laden three-dimensional (3D) scaffolds, which are used to fabricate complex 3D constructs and provide specific microenvironments for supporting cell growth and differentiation. The development of bioinks with appropriate printability and specific bioactivities is crucial for bioprinting and tissue engineering applications, including bone tissue regeneration. Therefore, to produce functional bioinks for osteoblast printing and bone tissue formation, we formulated various nanocomposite hydrogel-based bioinks using natural and biocompatible biomaterials (i.e., alginate, tempo-oxidized cellulose nanofibrils (TOCNF), and polydopamine nanoparticles (PDANPs)). Rheological studies and printability tests revealed that bioinks containing 1.5% alginate and 1.5% TOCNF in the presence or absence of PDANP (0.5%) are suitable for 3D printing. Furthermore, in vitro studies of 3D-printed osteoblast-laden scaffolds indicated that the 0.5% PDANP-incorporated bioink induced significant osteogenesis. Overall, the bioink consisting of alginate, TOCNF, and PDANPs exhibited excellent printability and bioactivity (i.e., osteogenesis).

Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads.

Hypoparathyroidism is an endocrine disorder that occurs because of the inability to produce parathyroid hormone (PTH) effectively. Previously, we reported the efficacy of tonsil-derived mesenchymal stem cells (TMSCs) differentiated into parathyroid-like cells for the treatment of hypoparathyroidism. Here, we investigated the feasibility of three-dimensional structural microbeads fabricated with TMSCs and alginate, a natural biodegradable polymer, to treat hypoparathyroidism. Alginate microbeads were fabricated by dropping a 2% (w/v) alginate solution containing TMSCs into a 5% CaCl2 solution and then differentiated into parathyroid-like cells using activin A and sonic hedgehog for 7 days. The protein expression of PTH, a specific marker of the parathyroid gland, was significantly higher in differentiated alginate microbeads with TMSCs (Al-dT) compared with in undifferentiated alginate microbeads with TMSCs. For in vivo experiments, we created the hypoparathyroidism animal model by parathyroidectomy (PTX) and implanted alginate microbeads in the dorsal interscapular region. The PTX rats with Al-dT (PTX+Al-dT) showed the highest survival rate and weight change and a gradual increase in serum intact PTH levels. We also detected a higher expression of PTH in retrieved tissues of PTX+Al-dT using immunofluorescence analysis. This study demonstrates that alginate microbeads are potential a new tool as a surgically scalable therapy for treating hypoparathyroidism.

Surface engineering of 3D-printed scaffolds with minerals and a pro-angiogenic factor for vascularized bone regeneration.

Scaffolds functionalized with biomolecules have been developed for bone regeneration but inducing the regeneration of complex structured bone with neovessels remains a challenge. For this study, we developed three-dimensional printed scaffolds with bioactive surfaces coated with minerals and platelet-derived growth factor. The minerals were homogeneously deposited on the surface of the scaffold using 0.01 M NaHCO3 with epigallocatechin gallate in simulated body fluid solution (M2). The M2 scaffold demonstrated enhanced mineral coating amount per scaffold with a greater compressive modulus than the others which used different concentration of NaHCO3. Then, we immobilized PDGF on the mineralized scaffold (M2/P), which enhanced the osteogenic differentiation of human adipose derived stem cells in vitro and promoted the secretion of pro-angiogenic factors. Cells cultured in M2/P showed remarkable ratio of osteocalcin- and osteopontin-positive nuclei, and M2/P-derived medium induced endothelial cells to form tubule structures. Finally, the implanted M2/P scaffolds onto mouse calvarial defects had regenerated bone in 80.8 ± 9.8% of the defect area with the arterioles were formed, after 8 weeks. In summary, our scaffold, which composed of minerals and pro-angiogenic growth factor, could be used therapeutically to improve the regeneration of bone with a highly vascularized structure. STATEMENT OF SIGNIFICANCE: Surface engineered scaffolds have been developed for bone regeneration but inducing the volumetric regeneration of bone with neovessels remains a challenge. In here, we developed 3D printed scaffolds with bioactive surfaces coated with bio-minerals and platelet-derived growth factors. We proved that the 0.01 M NaHCO3 with polyphenol in simulated body fluid solution enhanced the deposition of bio-minerals and even distribution on the surface of scaffold. The in vitro studies demonstrated that the attached cells on the bioactive surface showed the enhanced osteogenic differentiation and secretion of pro-angiogenic factors. Finally, the scaffold with bioactive surface not only improved the regenerated volume of bone tissues but also increased neovessel formation after in vivo implantation onto mouse calvarial defect.

Ultrasensitive Molecule Detection Based on Infrared Metamaterial Absorber with Vertical Nanogap.

Surface-enhanced infrared absorption (SEIRA) spectroscopy is a powerful methodology for sensing and identifying small quantities of analyte molecules via coupling between molecular vibrations and an enhanced near-field induced in engineered structures. A metamaterial absorber (MA) is proposed as an efficient SEIRA platform; however, its efficiency is limited because it requires the appropriate insulator thickness and has a limited accessible area for sensing. SEIRA spectroscopy is proposed using an MA with a 10 nm thick vertical nanogap, and a record-high reflection difference SEIRA signal of 36% is experimentally achieved using a 1-octadecanethiol monolayer target molecule. Theoretical and experimental comparative studies are conducted using MAs with three different vertical nanogaps. The MAs with a vertical nanogap are processed using nanoimprint lithography and isotropic dry etching, which allow cost-effective large-area patterning and mass production. The proposed structure may provide promising routes for ultrasensitive sensing and detection applications.

Effect of tannic acid on the mechanical and adhesive properties of catechol-modified hyaluronic acid hydrogels.

Hyaluronic acid (HA) is applied in various fields, including pharmaceutical science, owing to its favorable biological properties such as moisture retention, non-toxicity, biodegradability, biocompatibility and biodegradability. In particular, many studies have aimed at its application in the form of a hydrogel. However, the applications of HA hydrogels are limited owing to their poor mechanical properties. In this study, an HA-catechol conjugate (HA-Cat) was synthesized by reacting the HA polymer with dopamine to improve its adhesion to various substrates. The HA-Cat hydrogel was prepared via oxidative crosslinking using a small amount of NaIO4 as the oxidant, and the hydrogel formation was investigated by rheological and mechanical studies. Further, the effect of tannic acid (TA) on the adhesive strength and compressive strength of the HA-Cat/TA hydrogels was examined according to the amount of NaIO4 used for crosslinking and the TA contents. Both the adhesive and compressive properties of the HA-Cat hydrogels were improved with the addition of TA. The HA-based hydrogels containing TA have great potential as cost-effective and biocompatible medical adhesives.

Self-crosslinkable hyaluronate-based hydrogels as a soft tissue filler.

With increasing interest in aging and skin care, the use of fillers to increase the volume of soft tissue volume is increasing globally. However, the side effects caused by the residual chemical crosslinking agents present in these fillers limit the effective application of commercialized filler products. Therefore, the development of a novel crosslinking system with a non-toxic chemical crosslinking agent is required to overcome the limitations of commercial hyaluronate (HA)-based fillers. In this paper, a new injectable hydrogel with enhanced mechanical properties, tissue adhesion, injectability, and biocompatibility is reported. The HA derivatives modified with catechol groups (HA-DA) were crosslinked by self-oxidation under in vivo physiological conditions (pH 7.4) without chemical crosslinkers to form hydrogels, which can be further accelerated by the dissolved oxygen in the body. The fabricated HA-DA filler showed excellent mechanical properties and could be easily injected with a low injection force. Further, the HA-DA filler stably attached to the injection site due to the tissue adhesion properties of the catechol groups, thus leading to an improved displacement stability. In addition, the HA-DA filler showed excellent cell viability, cell proliferation, and biocompatibility. Therefore, the HA-DA hydrogel is a novel soft tissue filler with great potential to overcome the limitations of commercial soft tissue fillers.