For an implant to provide a strong solution as a replacement part, it is essential to bind strongly to the bone to which the implant is aligned. While titanium offers good osseointegration and corrosion resistance, it doesn't bond directly with bone due to its surface oxide layer which leaves a gap between the implant and the surrounding bone. In this study we investigate the enhancement of osseointegration in 3D-printed titanium implants using a polycrystalline diamond (PCD) coating. PCD coating aims to improve biocompatibility and bone integration. PCD coating of implants resulted in a microroughened surface (Ra 27 mu m vs 23 mu m for titanium) with nanofeatures resulting in a hydrophilic surface. In rabbit models, PCD-coated titanium implants showed improved bone response compared to titanium with superior bone in contact with the implant reflected by a 190N push out force (vs titanium at 155N, p < 0.5) needed to remove the implant from the bone. Our findings provide crucial insights into the interactions at the bone-implant interface, suggesting that PCD-coated titanium implants could significantly improve orthopaedic outcomes by promoting better integration and reducing infection risks.

ABSTRACT Natural bone contains various impurities such as magnesium, zinc, and strontium, which play a crucial role in bone remodeling. However, studies investigating the incorporation of these elements into polymeric scaffolds to mimic the natural bone formation process remain limited. In this study, magnesium‐substituted hydroxyapatite (Mg‐HA) nanoparticles are synthesized and incorporated into a polyvinyl alcohol/starch (PVA/ST) polymeric matrix to fabricate three‐dimensional Mg‐containing composite scaffolds. The effects of Mg incorporation on scaffold composite structure, properties, and potential application in bone regeneration are then investigated. The synthesized Mg‐HA powders are characterized in terms of Mg content by SEM‐EDS, phase composition by XRD, and particle size by FE‐SEM. The fabricated composite scaffolds are evaluated for pore size and architecture using SEM, whereas phase and elemental composition are analyzed by XRD and SEM‐EDS. In addition, compressive strength and open porosity are also determined. Biocompatibility of scaffolds is assessed by evaluating biomineralization, biodegradation in SBF solution, L929 cells‐materials interaction using XRD, TGA, scaffold mass loss, and SEM‐EDS. The results confirmed the successful synthesis of Mg‐substituted HA nanoparticles with sizes ranging from 40 to 120 nm and their subsequent incorporation into the PVA/ST matrix for the fabrication of three‐dimensional composite scaffolds. Moreover, the incorporation of Mg‐HA particles into PVA/ST scaffolds enhanced their biomineralization capability in SBF solution and promoted L929 cell adhesion and spreading.

Uncontrolled hemorrhage is still one of the most common causes of mortality in combat casualties and maternal death. Therefore, rapid and effective hemostasis is vital for ensuring the survival of patients. While hydrophilic hemostatic materials has been successful in achieving fast coagulation, they can still cause clot tears and secondary bleeding when removing dressing due to its high absorption rate. In the prevention of secondary bleeding and reducing blood loss, hydrophobic and superhydrophobic hemostatic dressings are being developed. In this study, a mixture of fixed PCL/COS content and increasing MMT concentration was electrospun to create hydrophobic hemostatic membranes. The membranes were evaluated on their morphology, wettability, mechanical strength, chemical composition, thermal property as well as hemostatic effect both in vitro and on animal models. The fabricated membranes have small fiber diameter of 20 - 140 nm, and low blood absorption compared to commercial zeolite gauze. The membrane exhibits more hydrophobicity with higher MMT content, with MMT80 having blood contact angle of 130.37 +/- 5.84 degrees. In vitro hemostasis test shows that MMT80 has better hemostatic efficiency compared to other MMT membranes. The bleeding time of the MMT80 sample reached 40.33 +/- 6.51 s, which is comparable to commercial gauze ACG while having significantly lower blood loss (54.37 +/- 41.01 mg) in in vivo experiment using mouse liver laceration model. Safety evaluation of MMT membranes indicated no adverse effect in cytotoxicity and hemolytic activity. The results prove that the hydrophobic PCL/COS/MMT membrane has great potential in hemostatic applications.

Cartilage lesions are common and have a finite ability to repair and regenerate due to the lack of blood, nerve, and lymph supplies. Current treatments employing biomaterials for cartilage regeneration are of limited effectiveness since most of them have to be shaped externally before introduction to the body. Also, implantation often requires open incisions, increasing the risk of infection and patient discomfort. Therefore, finding a favorable therapy to treat cartilage damage is imperative before joints are irritated further. During transplantation, stem cells should be encapsulated in the biocompatible matrix to prevent their death at the injury site, and further regeneration requires a combination of stem cells, scaffolds, and bioactive signals, also known as the triad of tissue engineering. Injectable hydrogels, playing as three-dimensional scaffolds, can support cell proliferation and regeneration of damaged tissues. Amongst them, self-crosslinking hydrogels, without the use of regular mass crosslinking agents, not only ensure non-toxicity for stem cells but also are an encouraging resolution for establishing injectable scaffolds. Among different in situ-crosslinking mechanisms, Schiff base linkage between amino and aldehyde groups is a potential manner for fabricating self-crosslinking hydrogels. Moreover, various natural biopolymers used for fabricating hydrogel can provide abundant functional groups to facilitate intra-network self-crosslinking establishment and mimic the extracellular matrix to promote stem cell adhesion, proliferation, and differentiation. Therefore, self-crosslinking hydrogels emerge as promising bioinks in cartilage tissue bioprinting. Following the general bioprinting process, the prepared hydrogel precursor/s (with cell addition) are put in a syringe or nozzle of the bioprinter and dispersed over the platform along the route directed by the proposed model at temperatures ranging from 0 ℃ to 90 ℃ (usually body temperature). Finally, self-crosslinking hydrogels form mechanically stable structures, which are then characterized to ensure their validity for later applications.

Cartilage tissue regeneration remains challenging due to the tissue's poor self-healing capacity, attributed to its hypocellular and avascular nature, which limits nutrient delivery to the defect site and complicates healing. Traditional methods often utilize the subchondral tissue layer to improve nutrient exchange through its vascular network, although these approaches have limitations. To address these issues, 3-dimensional (3D) printing has been employed to create the bilayered scaffold that mimics the complex structure of osteochondral tissue. In this study, the N,O-carboxymethyl chitosan (NOCC) and oxidized xanthan gum (OXG) hydrogel was fabricated for the cartilage layer due to its similarity to the native cartilage structure, while the biphasic calcium phosphate (BCP) incorporation enhanced the osteoconductivity to promote new bone growth for osteochondral tissue regeneration. Various characterization tests, including compression strength, scanning electron microscopy analysis, and biological properties, were conducted to evaluate and balanced to achieve the highest regenerative capacity for implantation. No cytotoxicity was caused, while the in vitro testing highlighted that the addition of BCP considerably supported cellular behavior on the scaffold and improved the regeneration rate. With 60% BCP content, the 3D scaffold demonstrated a high osteochondral tissue regeneration rate, as evidenced by visual inspection, x-ray imaging, and histological analysis, outperforming other experimental models.

Three-dimensional (3D) bio-printing technology involves printing biological materials in a 3D space using the additive manufacturing method and computer-aided design. In this study, we used natural polymeric hydrogels as bio-inks as they can mimic the extracellular matrix environment, supporting cell proliferation and differentiation. This study aims to determine the appropriate printing conditions for various hydrogel systems to fabricate 1 cm3 cube structure. To produce bio-inks, we have utilized the Schiff base reaction mechanism by covalently bonding the amine groups in N,O-carboxymethyl chitosan (NOCC) with the aldehyde groups in other oxidized polysaccharides such as oxidized xanthan gum (OXG), aldehyde hyaluronic acid (AHA), and oxidized alginate (OA). The bio-inks, namely NOCC-OXG, NOCC-AHA, NOCC-AHA-Alg, and NOCC-AHA-OA, were evaluated for their printability. The 3DPL Bioprinter N2+ with extrusion printing technology was used in this study. We delved into important design parameters of the fabricated bio-inks, including printing speed, infill percentage, printing trajectory, nozzle size, and extrusion pressure. Based on our findings, a printing speed of 550–750 mm/min is suitable for every bio-ink. The printing pressures for the NOCC-OXG range from 1.8 to 2 MPa, for NOCC-AHA from 0.5 to 0.7 MPa, for NOCC-AHA-Alg from 0.8 to 1 MPa, and for NOCC-AHA-OA from 1.3 to 1.6 MPa. Furthermore, the surface morphology of the bio-inks demonstrated a porous structure with a high degree of porosity, which can support the process of cell proliferation. The NOCC-OXG with 25G nozzle produced the most stable printed strands among different bio-ink systems. The results also exhibited that the compression strength of the NOCC-OXG gel system was 31–37 kPa, which is suitable for hard tissue. On the other hand, the NOCC-AHA-OA gel system is appropriate for fabricating more elastic tissue with compression stress of 10–18 kPa. Overall, these findings provide valuable insights for future biomedical research.

Naturally derived Schiff-based hydrogels are widely fabricated for tissue engineering applications. However, limited studies have explored how the physicochemical and functional groups on polymer chains affect cell behavior in three dimensions. To address this limitation, we fabricated cytocompatible N-O carboxymethyl chitosan (NOCC) cross-linked with oxidized xanthan gum (OXG), incorporating various aldehyde (-CHO) contents (NO1, NO2, and NO3) while maintaining a constant concentration of NOCC, resulting in hydrogels with diverse viscoelastic and aldehyde content properties. The results demonstrated significant differences in storage modulus (G') and loss modulus (G″), attributed to cross-linking density through imine bonds (-C═N-). These differences influenced murine fibroblast aggregation, spheroid formation, and cell migration, proliferation, and viability over time. Both NO1 and NO2 exhibited good cell viability, with slight differences in spheroid morphology compared to those of NO3 and Matrigel samples. To further explore cell behaviors, integrin αV (CD51) expression was assessed using fluorescence-activated cell sorting (FACS) and immunofluorescence. The results aligned with prior observations, with the quantitative analysis of integrin αV expression, normalized to 4',6-diamidino-2-phenylindole (DAPI) fluorescence, revealing a notable 2.1-fold increase in fluorescence intensity for the NO2 hydrogel in comparison to NO1 (p < 0.0001). These findings indicate that the hydrogel composed of 2% (w/v) NOCC cross-linked with 2% (w/v) OXG in a 1:1 (v/v) ratio represents the optimal condition for promoting murine fibroblast growth and spheroid formation. These results provide a robust foundation for future research aimed at modulating cell behavior through precise adjustments of scaffold properties, thereby advancing the potential for translational applications from laboratory research to clinical settings.

This study fabricates and characterizes novel double-network hydrogels for 3D bio-ink applications, combining N,O-carboxymethyl chitosan (NOCC), aldehyde hyaluronate (AHy), and alginate (Alg). The initial Schiff base-cross-linked network (NOCC-AHy-Alg) is enhanced with a second ionic Ca2+ cross-linking, optimized via an internal suspension method (CaCO3/glucono-δ-lactone). Optimal parameters are 0.2 m CaCO3 and 0.1 m glucono-δ-lactone with a 1-h immersion, proving superior to external CaCl2 immersion. This internal approach yields a more robust network with improved compressive strength, dimensional stability, and lower porosity, requiring sustained Ca2+ for long-term stability. The hydrogels also demonstrate excellent self-recovery and energy dissipation, indicating potential for 3D printing. In vitro studies confirm biocompatibility with L929 and AT-MSCs. Overall, these double-network hydrogels show significant promise as advanced bio-inks for tissue engineering and other biomedical uses.

Injectable hydrogels have emerged as promising biomaterials for various biomedical applications. However, limitations such as weak mechanical properties, limited injectability, and lack of self-healing ability hinder their widespread use. This study developed a novel injectable hydrogel based on oxidized xanthan gum and amino-modified carboxymethyl cellulose to address these challenges. These hydrogels exhibited rapid gelation, tunable mechanical properties, self-healing capabilities, controlled degradation, and excellent biocompatibility by employing dynamic acyl hydrazone bonds. Comprehensive characterization, including FTIR, 1H-NMR, rheological studies, and mechanical testing, confirmed the successful formation of hydrogels with desirable properties. The hydrogels demonstrated rapid gelation times of approximately 5 s and remarkable compressive strengths exceeding 500 kPa. Rheological studies revealed excellent injectability and the ability to maintain solid-state properties under shear deformation. Significantly, the hydrogels exhibited over 90

Bone tissue engineering is a promising technology being studied globally to become an effective and sustainable method to treat the problems of damaged or diseased bones. In this work, we developed an in situ cross-linking hydrogel system that combined N-succinyl chitosan (NSC) and oxidized alginate (OA) at varying mixing ratios through Schiff base cross-linking. The hydrogel system also contains biphasic calcium phosphate (BCP) and ascorbic acid (AA), which could enhance biological characteristics and accelerate bone repair. The hydrogels' properties were examined through physicochemical tests such as scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), pore size and porosity measurement, swelling ratio, degradation rate, AA release study, as well as cytocompatibility, including live/dead and cytotoxicity assays. The results revealed that the supplementation of AA and BCP components can affect the physico-mechanical properties of the hydrogel system. However, they exhibited noncytotoxic properties. Overall, the results demonstrated that the hydrogel composed of 3% (w/v) NSC and 3% (w/v) OA (NSC: OA volume ratio is 8:2) loaded with 40% (w/w) BCP and 0.3 mg/mL AA has the potential for bone regeneration.

Hydrogels have emerged as potential materials for bone grafting, thanks to their biocompatibility, biodegradation, and flexibility in filling irregular bone defects. In this study, we fabricated a novel NAH hydrogel system, composed of N,O-carboxymethyl chitosan (NOCC), aldehyde hyaluronic acid (AHA), and hydroxyapatite (HAp). To improve the mechanical strength of the fabricated hydrogel, a porous polycaprolactone (PCL) matrix was synthesized and used as a three-dimensional (3D) support template for NAH hydrogel loading, forming a novel PCL/NAH hybrid scaffold. A mixture of monosodium glutamate (M) and sucrose (S) at varied weight ratios (5M:5S, 7M:3S, and 9M:1S) was used for the fabrication of 3D PCL matrices. The morphology, interconnectivity, and water resistance of the porous PCL scaffolds were investigated for optimal hydrogel loading efficiency. The results demonstrated that PCL scaffolds with porogen ratios of 7M:3S and 9M:1S possessed better interconnectivity than 5M:5S ratio. The compressive strength of the PCL/NAH hybrid scaffolds with 9M:1S (561.6 ± 6.1 kPa) and 7M:3S (623.8 ± 6.8 kPa) ratios are similar to cancellous bone and all hybrid scaffolds were biocompatible. Rabbit models with tibial defects were implanted with the PCL/NAH scaffolds to assess the wound healing capability. The results suggest that the PCL/NAH hybrid scaffolds, specifically those with porogen ratio of 7M:3S, exhibit promising bone healing effects.

3D bioprinting is a new technology used in medicine to create complex biomimetic structures for applications in tissue engineering, regenerative medicine, and drug testing. The selection of materials for the bio-ink, a printable formulation, plays an important role in optimizing the 3D bioprinting process in accordance with the research objectives. Polymers, especially hydrogels, produce bio-inks with fascinating properties that can be manipulated artificially. We propose a hydrogel system combining N, O-carboxymethyl chitosan (NOCC) with oxidized xanthan gum (OXG) with different volume ratios to improve the mechanical properties. We incorporated NOCC and OXG into hydrogels, and confirmed by Fourier-transform infrared spectroscopy (FTIR) method. The change in the NOCC:OXG ratio affects the pore size, mechanical strength, and swelling of the hydrogel. NOCC/OXG hydrogel has a low endotoxin value and is not toxic to fibroblast cells. We recommend further studies to apply NOCC/OXG hydrogel in bio-ink.

Hemorrhagic shock is the leading cause of preventable deaths in traumatic accidents, emphasizing the significance of hemostasis-promoting materials and their incorporation into a pre-hospital medical response system. Bacterial cellulose has drawn much attention in tissue engineering due to its versatility and biocompatibility. In this study, a hemostatic dressing was composed of bacterial cellulose (BC) and chitosan oligosaccharide (COS), which is a well-known biological agent. The influence of chitosan oligosaccharide on the morphology, chemical, and physical properties of the fabricated cellulose membranes was evaluated. Additionally, the hemostatic performance of BC-COS membranes was investigated through in vitro and in vivo experiments. The results show that the addition of COS led to a lower mechanical strength while increasing the hemostatic properties of the BC membrane. The BC membrane modified with 2 w/v% COS solution (BC-COS2) demonstrated excellent hemostasis promotion through whole blood assays and mice hemorrhage model. The blood clotting index and blood clotting time of the BC-COS2 sample reached 86.25% and 190 s, respectively. Furthermore, in the in vivo experiments, the group treated using BC-COS2 also presented much lower bleeding stop time and blood loss compared to the untreated group. The results reveal the viability of the cellulosic material as a potential hemostatic dressing.

Artificial vascular transplantation is one of the potential state-of-the-art therapies for cardiovascular diseases, which are known as a leading cause of death worldwide. With the development of vascular tissue engineering, researchers have succeeded in creating large-caliber vascular structures. However, the challenges of fabricating artificial blood vessels less than 6 mm in diameter remain unsolved. In this study, we fabricated tubular structures of this size from blended polyurethane/polycaprolactone nanofibers coated with anti-thrombogenic agents and lined with endothelial cells. The polymeric structure from those two cytocompatible polymers demonstrated suitable physical properties as a vascular graft. Further investigation on cell-material interaction with bovine artery endothelial cells established that the conjugated linoleic acid-grafted scaffold supported monolayer endothelial proliferation while limiting platelet adhesion. This approach could pave a way for developing a promising therapeutic method of artificial vascular transplantation that effectively overcomes occlusion.

Mineralized hydrogels, synthesized by incorporating mineral particles into the hydrogel crosslinking network, have become an effective approach for bone tissue engineering. In this study, hydrogel composites based on alginate, N,O-carboxymethyl chitosan (NOCC), aldehyde hyaluronic acid (AHA) and loaded with biphasic calcium phosphate (BCP) were fabricated by in situ crosslinking. NOCC-AHA hydrogel, forming crosslinks by Schiff base reaction without requiring any chemical linkers or radial light sources, offers a porous scaffold favorable for incorporating with the mineral phase. The integration of BCP – inorganic phase – and alginate within the NOCC-AHA system can be used to supplement mineral agents and reinforcement. Different amounts of BCP particles were investigated to improve cell proliferation. The formation of hydrogel composites was confirmed via scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). In vitro study evidenced that MC3T3 cells were well-attached to hydrogel composites which did not cause cytotoxicity. Furthermore, in vivo study demonstrated that alginate-NOCC-AHA-BCP hydrogels promoted bone healing in the full-thickness calvarial defect mouse model. The obtained results indicated that the fabricated hydrogel composite could be a potential material for bone regeneration with a suitable degradation rate, appropriate pore size, favorable cytocompatibility, high compressive strength, ability to support cell proliferation, and capacity to enhance bone regeneration.

In the management of burn wounds, antimicrobial and wound healing properties are crucial. In this study, we prepared a three-layer electrospun poly(ε-caprolactone) (PCL) membrane for burn wound dressing. The hydrophobic electrospun PCL layer, embedded with silver nanoparticles (SNPs) (PCL-Ag), was coated with another layer of electrospun plasma-treated PCL-Ag to enhance the wettability of the membrane. This enhancement was to facilitate the absorption of the hydrophilic chitosan oligomer (COS) - the third layer of the dressing. The resultant membranes were characterised and tested for different properties to demonstrate their applicability as wound dressing materials. The combination of COS and SNPs of the fabricated membrane supports the healing process and reduces burn severity due to the healing capacity of COS and the antibacterial activity of SNPs, without compromising mechanical strength. We conducted several in vitro and in vivo experiments to evaluate its applicability for burn wound healing. The PCL-Ag/COS sample demonstrated outstanding in vitro biocompatibility and excellent antibacterial activity against Staphylococcus aureus strains. We used the membrane to treat burns on rabbits in the laboratory over 30 days, and consistently observed positive outcomes. This research offers insights into the development of bioactive dressings for wound healing and opens up opportunities for practical applications of COS-incorporated materials.

Dynamic hydrogel systems from N,O-carboxymethyl chitosan (NOCC) are investigated in the past years, which has facilitated their widespread use in many biomedical engineering applications. However, the influence of the polymer's oxidation levels on the hydrogel biological properties is not fully investigated. In this study, chitosan is converted into NOCC and introduced to react spontaneously with oxidized xanthan gum (OXG) to form several injectable hydrogels with controlled degradability. Different oxidation levels of xanthan gum, as well as NOCC/OXG volume ratios, are trialed. The infrared spectroscopy spectra verify chemical modification on OXG and successful crosslinking. With increasing oxidation levels, more dialdehyde groups are introduced into the OXG, resulting in changes in physical properties including gelation, swelling, and self-healing efficiency. Under different volume ratios, the hydrogel shows a stable structure and rigidity with higher mechanical properties, and a slower degradation rate. The shear-thinning and self-healing properties of the hydrogels are confirmed. In vitro assays with L929 cells show the biocompatibility of all formulations although the use of a high amount of OXG15 and OXG25 limited the cell proliferation capacity. Findings in this study suggested a suitable amount of OXG at different oxidation levels in NOCC hydrogel systems for tissue engineering applications.

An ideal wound dressing should have several qualities to protect the wound from infection and other adverse factors. This study aimed to fabricate a wound care membrane combining the two well-known bioactive agents silver nanoparticles (AgNPs) and chitosan oligosaccharides (COS). In specific, this multilayer membrane (PCL-Ag/POX/COS) consisted of (1) the electrospun basement layer of poly(epsilon-caprolactone) (PCL) and AgNPs; (2) the intermediate amphiphilic layer of PCL and poloxamer 407 (POX); and (3) the coating layer of COS and poly(N-vinyl pyrrolidone) (PVP). Several characterisation tests showed that the membrane was successfully coated with COS and owned suitable characteristics as a wound dressing, including proper tensile strength (more significant than the typical value of the skin), the hydrophilic and fluid-absorbable innermost surface, the waterproof outermost basement, vapour permeability, rapid COS release, and gradual AgNP release. In vitro experiments proved its haemostatic effect and antibacterial activities. Though its 100% extract solution reduced in vitro fibroblast viability, through the skin-defected mouse model experiment, PCL-Ag/POX/COS was compatible with the wound tissue and exhibited several positive effects on wound healing. In conclusion, PCL-Ag/POX/COS was proven for its potential for wound care, but it needs further investigations to allow translation from bench to bedside. (c) 2023 Vietnam National University, Hanoi. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

One of the most common causes of high mortality in Vietnam, as well as in the world, is related to cardiovascular disease. Therefore, the development of artificial blood vessels to replace damaged blood vessels in cardiovascular patients has become increasingly necessary. Realizing a growing need for these techniques, our team manufactured a specialized electrospinner machine to produce artificial blood vessel models. The electrospinner has the following components: high power supply source, collectors with tubular-type structures, and a syringe pump system. This study was conducted to (i) fabricate electrospinner machine and (ii) operate and evaluate the electrospinner. We found that the conditions of vascular formation can be optimized and these influencing parameters include DC high voltage source, distance between needle tip and collector, needle tip diameter, speed of syringe pump, and ambient temperature and humidity. The results show that this equipment is stable and safe for users.