Search Results (96)

Xenogenic collagen matrices are used in clinical practice for soft tissue augmentation around teeth and implants, either alone or biofunctionalized with injectable platelet-rich fibrin (iPRF). Their direct interaction with inflammatory cells may influence both healing and destructive inflammation processes. Therefore, expression of cyclooxygenases (COX-1 and COX-2) and prostanoids (PGE2 and TXB2) was studied in THP-1 monocyte/macrophage cultures exposed to porcine collagen matrices (a non-cross-linked monolayer scaffold composed of collagen type I, collagen type III, and elastin (MLCM), a bilayer scaffold made of collagen types I and III (BLCM), and a volume-stable cross-linked monolayer scaffold (VSCM)). The study showed that VSCM and MLCM significantly reduced PGE2 concentrations in THP-1 monocyte cultures. iPRF further reduced PGE2 concentrations when exposed to MLCM. In contrast, incubation of THP-1 monocytes with VSCM and BLCM resulted in a significant increase in TXB2 concentrations compared with control conditions. Incubation of macrophages with MLCM, VSCM, and BLCM increased PGE2 concentrations, with VSCM and BLCM additionally increasing TXB2 concentrations. iPRF in macrophage cultures with VSCM and BLCM also resulted in increased PGE2 and TXB2 concentrations compared with control conditions. Confocal microscopy revealed no visible differences in COX-1 immunoexpression in monocytes and macrophages cultured with collagen matrices, either with or without iPFR. Weak positive COX-2 immunofluorescence was observed in monocytes, while moderate positive immunofluorescence was detected in macrophages. In conclusion, it can be suggested that the studied collagen matrices interact with monocytes/macrophages, with MLCM exhibiting the highest compatibility. Full article

Articular cartilage has limited regenerative potential due to its anatomical characteristics, making complete recovery from damage challenging. Microfracture (MFx) is a widely used technique to promote cartilage healing, often enhanced with scaffolds to improve outcomes. In this study, we compared the efficacy of bilayer atelocollagen and standard collagen scaffolds combined with MFx in treating osteochondral defects in a rabbit model. Three articular cartilage defects were created in the femoral condyle of each rabbit and treated with either MFx plus a bilayer atelocollagen scaffold (test group), MFx plus a standard collagen scaffold (positive group), or MFx alone (negative group). Macroscopic and histological assessments were performed at 3, 6, and 12 weeks. By week 12, macroscopic examination showed hyaline-like cartilage restoration in the test group, while the positive group exhibited restoration with some overgrowth, and the negative group showed no restoration. Histological analysis revealed significantly better restoration in the test group than in the negative group, with comparable outcomes between the test and positive groups. These findings suggest that bilayer atelocollagen scaffold implantation following MFx is a promising treatment for articular cartilage defects and may provide a viable therapeutic option for patients with cartilage damage. Full article

A novel bi-layered scaffold, obtained via 3D printing and electrospinning, was designed to improve osteochondral region reconstruction. The upper electrospun membrane will act as a barrier against unwanted tissue infiltration, while the lower 3D-printed layer will provide a porous structure for tissue ingrowth. Graphene was integrated into the scaffold for its antibacterial properties, and the drug Osteogenon^® (OST) was added to promote bone tissue regeneration. The composite scaffolds were subjected to comprehensive physical, thermal, and mechanical evaluations. Additionally, their biological functionality was assessed by means of NHAC-kn cells. The 0.5% graphene addition to PCL significantly increased strain at break, enhancing the material ductility. GNP also acted as an effective nucleating agent, raising crystallization temperatures and supporting mineralization. The high surface area of graphene facilitated rapid apatite formation by attracting calcium and phosphate ions. This was confirmed by FTIR, µCT and SEM analyses, which highlighted the positive impact of graphene on mineral deposition. The synergistic interaction between graphene nanoplatelets and Osteogenon^® created a bioactive environment that enhanced cell adhesion and proliferation, and promoted superior apatite formation. These findings highlight the scaffold’s potential as a promising biomaterial for osteochondral repair and regenerative medicine. Full article

Osteochondral defects, involving both articular cartilage and subchondral bone, pose significant challenges to joint function and health due to the lack of spontaneous healing and the risk of long-term degenerative diseases like osteoarthritis. Biomaterials have emerged as important components in the development of scaffolds, providing structural support that facilitates tissue growth, integration, and regeneration. This study aims to demonstrate the effectiveness of a tomographic assessment method for optimizing the evaluation of osteochondral regeneration, particularly using Hounsfield units, to enable the evaluation of scaffold integration and tissue regeneration. The sheep model was selected as a model study. Two distinct configurations of biomaterials were utilized in this study: Honey (HMG—Mg doped hydroxyapatite; HWS—wollastonite–hydroxyapatite) and Bi-layer (BWS—wollastonite–hydroxyapatite). The HMG scaffold demonstrated superior integration, reparative tissue quality, and regeneration potential compared to the HWS, BWS, and CTRL groups. The findings underscore the significance of CT assessment as a preliminary method for evaluating hard tissue, such as bone, employing Hounsfield units. Statistical evaluations validated the significant differences in performance, particularly favoring the HMG group. The results of this study underscore the importance of tomographic assessment in evaluation of osteochondral regeneration. Full article

ABC toxin complexes (Tcs) are tripartite complexes that come together to form nano-syringe-like translocation systems. ABC Tcs are often compared with Bacillus thuringiensis (Bt) toxins, and as such, they have been highly studied as a potential novel pesticide to combat growing insect resistance. Moreover, it is possible to substitute the cytotoxic hypervariable region with alternative peptides, which promise potential use as a novel peptide delivery system. These toxins possess the unique ability to form active chimeric holotoxins across species and display the capability to translocate a variety of payloads across membrane bilayers. Additionally, mutagenesis on the linker region and the receptor binding domains (RBDs) show that mutations do not inherently cause a loss of functionality for translocation. For these reasons, Tcs have emerged as an ideal candidate for targeted protein engineering. However, elucidation of the specific function of each RBD in relation to target receptor recognition currently limits the use of a rational design approach with any ABC Tc. Additionally, there is a distinct lack of targeting and biodistribution data for many Tcs among mammals and mammalian cell lines. Here, we outline two separate strategies for modifying the targeting capabilities of the A subunit (TcA) from Xenorhabdus nematophilus, Xn-XptA2. We identify novel structural differences that make Xn-XptA2 different than other characterized TcAs and display the modular capabilities of substituting RBDs from alternative TcAs into the Xn-XptA2 scaffold. Finally, we show the first, to our knowledge, biodistribution data of any TcA in mice. Full article

Objective: The aim of this study was to evaluate the cure efficiency and biocompatibility of a novel iron-based coordination complex used as a photoinitiator in comparison to conventional ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPO-L) and camphorquinone (CQ) as photoinitiators in dental 3D-printed resins. Materials and Methods: Experimental dental resin formulations were prepared by blending 1:1 ratio of Bis-GMA and TEGDMA, to which 0.2 wt% of either the iron-based coordination complex or CQ were added, along with 0.2 wt% EDAB and 0.4 wt% IOD, and the TPO-L. The degree of conversion (DC) was measured using Fourier transform infrared spectroscopy (FTIR). Biocompatibility was assessed by evaluating the viability of L929 fibroblast-like cells using the MTT assay 24 h post-exposure. Statistical analyses included a two-way ANOVA followed by Tukey’s test for post hoc comparisons, with significance at p < 0.05. Results: The degree of conversion for the iron-based coordination complex (84.54% ± 1.69%) was significantly higher than that for the TPO-L (78.77% ± 1.25%) and CQ-based resins (73.21% ± 0.47%) (p < 0.001). The iron-based coordination complex and TPO-L resins exhibited significantly higher conversion than CQ-based resins (p < 0.001). Regarding biocompatibility, the cell viability test revealed that the iron-based coordination complex demonstrated the highest cell viability at 86.5% ± 10.24%, followed by TPO-L with 80.03% ± 11.07%. CQ showed the lowest cell viability of 51.29% ± 8.44% (p < 0.05). Tukey’s test confirmed significant differences between CQ and other photointiators (p < 0.05), while no significant difference was found between TPO-L and the iron-based coordination complex. Conclusions: This study introduces a novel iron-based coordination complex photoinitiator that demonstrates enhanced cure efficiency and comparable biocompatibility to TPO-L, while significantly reducing the cytotoxicity associated with CQ. Its longer absorption wavelength supports deeper layer curing, making it a promising alternative for dental 3D printing, particularly in bioactive scaffold applications requiring minimized cytotoxicity. Full article

In this study, we synthesized a series of 3-hydroxy-4-pyridinone (3,4-HPO) chelators with varying lipophilicity by modifying the length of their alkyl chains. To investigate their interaction with lipid membranes, we employed differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy using dimyristoylphosphatidylcholine (DMPC) and palmitoyloleoylphosphatidylcholine (POPC) liposomes as membrane model systems. DSC experiments on DMPC liposomes revealed that hexyl-substituted chelators significantly altered the thermotropic phase behavior of the lipid bilayer, indicating their potential as membrane property modulators. EPR studies on DMPC and POPC liposomes provided detailed insights into the depth-dependent effects of chelators on membrane fluidity. Our findings highlight the crucial role of alkyl chain length in determining the interaction of 3,4-HPO chelators with lipid membranes and offer valuable insights for the design of lipid-interacting therapeutic agents based on this scaffold. Full article

This study explored extrusion-based 3D bioprinting as a method for depositing cell-laden bio-ink to create well-defined scaffolds for tissue regeneration. Natural hydrogels, known for their biocompatibility and low cell toxicity, were favored for bio-ink formulation in this process. However, their limited mechanical strength poses a challenge to maintaining structural integrity. To address this, the rheological properties of hybrid hydrogels containing cellulose-derived nanofiber (TONFC) at concentrations between 0.5% and 1.0%, along with alginate and gelatin at levels between 2% and 5%, were tested in this study. A total of eight formulations was created by adjusting the proportions of alginate, TO-NFC, and gelatin, resulting in a combined solid content of 8%. Various rheological properties, such as the flow behavior, recovery rate, and linear viscoelastic range, were analyzed. Bi-layer scaffolds were 3D printed with various compositions and the shape fidelity was investigated. Human mesenchymal stem cells (hMSCs) were mixed to prepare bio-ink and cell survivability was observed after 7 incubation days. The ability to control 3D printability and the favorable survival of cells make nanofiber-infused alginate–gelatin a promising option for creating precisely shaped scaffolds using the 3D bio-printing process. Full article

Wound healing is important for skin after deep injuries or burns, which can lead to hospitalization, long-term morbidity, and mortality. In this field, tissue-engineered skin substitutes have therapy potential to assist in the treatment of acute and chronic skin wounds, where many requirements are still unmet. Hence, in this study, a novel type of biocompatible ternary polymer hybrid hydrogel scaffold was designed and produced through an entirely eco-friendly aqueous process composed of carboxymethyl cellulose, chitosan, and polyvinyl alcohol and chemically cross-linked by citric acid, forming three-dimensional (3D) matrices, which were biofunctionalized with L-arginine (L-Arg) to enhance cellular adhesion. They were applied as bilayer skin biomimetic substitutes based on human-derived cell cultures of fibroblasts and keratinocytes were seeded and grown into their 3D porous structures, producing cell-based bio-responsive hybrid hydrogel scaffolds to assist the wound healing process. The results demonstrated that hydrophilic hybrid cross-linked networks were formed via esterification reactions with the 3D porous microarchitecture promoted by foam templating and freeze-drying. These hybrids presented chemical stability, physicochemical properties, high moisture adsorption capacity, surface properties, and a highly interconnected 3D porous structure well suited for use as a skin substitute in wound healing. Additionally, the surface biofunctionalization of these 3D hydrogel scaffolds with L-arginine through amide bonds had significantly enhanced cellular attachment and proliferation of fibroblast and keratinocyte cultures. Hence, the in vivo results using Hairless mouse models (an immunocompromised strain) confirmed that these responsive bio-hybrid hydrogel scaffolds possess hemocompatibility, bioadhesion, biocompatibility, adhesiveness, biodegradability, and non-inflammatory behavior and are capable of assisting the skin wound healing process. Full article

Over the past two decades, the development of nerve guide conduits (NGCs) has gained much attention due to the impellent need to find innovative strategies to take care of damaged or degenerated peripheral nerves in clinical surgery. In this view, significant effort has been spent on the development of high-performance NGCs by different materials and manufacturing approaches. Herein, a highly versatile and easy-to-handle route to process 3D porous tubes made of chitosan and gelatin to be used as a nerve guide conduit were investigated. This allowed us to fabricate highly porous substrates with a porosity that ranged from 94.07 ± 1.04% to 97.23 ± 1.15% and average pore sizes—estimated via X-ray computed tomography (XCT) reconstruction and image analysis—of hundreds of microns and an irregular shape with an aspect ratio that ranged from 0.70 ± 0.19 to 0.80 ± 0.15 as a function of the chitosan/gelatin ratio. More interestingly, the addition of gelatin allowed us to modulate the mechanical properties, which gradually reduced the stiffness—max strength from 0.634 ± 0.015 MPa to 0.367 ± 0.021 MPa—and scaffold toughness—from 46.2 kJ/m³ to 14.0 kJ/m³—as the gelatin content increased. All these data fall into the typical ranges of the morphological and mechanical parameters of currently commercialized NGC products. Preliminary in vitro studies proved the ability of 3D porous tubes to support neuroblastoma cell (SH-SY5Y) adhesion and proliferation. In perspective, the proposed approach could also be easily implemented with the integration of other processing techniques (e.g., electrospinning) for the design of innovative bi-layered systems with an improved cell interface and molecular transport abilities. Full article

Scaffolds are widely used devices for the treatment of osteochondral lesions of the talus (OCLT), aimed at enhancing mechanical stability and fostering chondrogenic differentiation. A systematic review and meta-analysis were performed to evaluate the safety, and clinical and radiological results of scaffolds for OCLT management. On 2 January 2024, a search was performed in four databases (PubMed, Embase, Web of Science, and Scopus), according to PRISMA guidelines. The risk of bias in the included studies was also evaluated. Thirty clinical studies were included in the qualitative analysis: 12 retrospective case series, 3 retrospective comparative studies, 9 prospective case series, 1 prospective comparative study, and 1 Randomized Controlled Trial (RCT). Natural scaffolds, such as bilayer collagen (COLL)I/III and hyaluronic scaffolds, were the most employed. Only minor adverse events were observed, even if more serious complications were shown, especially after medial malleolar osteotomy. An overall clinical and radiological improvement was observed after a mean of 36.3 months of follow-up. Patient age and Body Mass Index (BMI), lesion size, and location were correlated with the clinical outcomes, while meta-analysis revealed significant improvement in clinical scores with hyaluronic scaffolds compared to microfracture alone. This study highlights the safety and positive clinical outcomes associated with the use of scaffolds for OCLT. In the few available comparative studies, scaffolds have also demonstrated superior clinical outcomes compared to microfractures alone. Nevertheless, the analysis has shown the limitations of the current literature, characterized by an overall low quality and scarcity of RCTs. Full article

Bioresorbable magnesium-metal vascular stents are gaining popularity due to their biodegradable nature and good biological and mechanical properties. They are also suitable candidate materials for biodegradable stents. Due to the rapid degradation rate of Mg metal vascular scaffolds, a Mg/Zn bilayer composite was formed by a number of means, such as magnetron sputtering and physical vapor deposition, thus delaying the degradation time of the Mg metal vascular scaffolds while providing good radial support for the stenotic vessels. However, the interlaminar compounds at the metal interface have an essential impact on the mechanical properties of the bi-material interface, especially the cracking and delamination of the Mg matrix Zn coating vascular stent in the radially expanded process layer. Intermetallic compounds (IMCs) are commonly found in dual-layer composites, such as Mg/Zn composites and multi-layer structures. They are frequently overlooked in simulations aiming to predict mechanical properties. This paper analyses the interfacial failure processes and evolutionary mechanisms of interfacial fracture mechanics of a Mg/Zn interface with an intermetallic compound layer between coated Zn and Mg matrix metallic vascular stents. The simulation results show that the fracture mode in the Mg/Zn interface with an intermetallic compound involves typical ductile fracture under static tensile conditions. The dislocation line defects mainly occur on the side of the Mg, which induces the Mg/Zn interfacial crack to expand along the interface into the pure Mg. The stress intensity factor and the critical strain energy release rate decrease as the intermetallic compound layer’s thickness gradually increases, indicating that the intensity of stress and the force of the crack extending and expanding along the crack tip are weakened. The presence of intermetallic compounds at the interface can significantly strengthen the mechanical properties of the material interface and alleviate the crack propagation between the interfaces. Full article

Biomaterials play an important role in treating bone defects. The functional characteristics of scaffolds, such as their structure, mechanical strength, and antibacterial and osteogenesis activities, effectively promote bone regeneration. In this study, mineralized collagen and polycaprolactone were used to prepare loaded porous scaffolds with bilayer-structured microspheres with dual antibacterial and osteogenesis functions. The different drug release mechanisms of PLGA and chitosan in PLGA/CS microspheres caused differences in the drug release models in terms of the duration and rate of Pac-525 and BMP-2 release. The prepared PLGA_(BMP-2)/CS_(Pac-525)@MC/PCL scaffolds were analyzed in terms of physical characteristics, bioactivity, and antibacterial properties. The scaffolds with a dimensional porous structure showed similar porosity and pore diameter to cancellous bone. The release curve of the microspheres and scaffolds with high encapsulation rates displayed the two-stage release of Pac-525 and BMP-2 over 30 days. It was found that the scaffolds could inhibit S. aureus and E. coli and then promote ALP activity. The PLGA_(BMP-2)/CS_(Pac-525)@MC/PCL scaffold could be used as a dual delivery system to promote bone regeneration. Full article

The wound healing mechanism is dynamic and well-orchestrated; yet, it is a complicated process. The hallmark of wound healing is to promote wound regeneration in less time without invading skin pathogens at the injury site. This study developed a sodium–carboxymethylcellulose (Na-CMC) bilayer scaffold that was later integrated with silver nanoparticles/graphene quantum dot nanoparticles (AgNPs/GQDs) as an acellular skin substitute for future use in diabetic wounds. The bilayer scaffold was prepared by layering the Na-CMC gauze onto the ovine tendon collagen type 1 (OTC-1). The bilayer scaffold was post-crosslinked with 0.1% (w/v) genipin (GNP) as a natural crosslinking agent. The physical and chemical characteristics of the bilayer scaffold were evaluated. The results demonstrate that crosslinked (CL) groups exhibited a high-water absorption capacity (>1000%) and an ideal water vapour evaporation rate (2000 g/m² h) with a lower biodegradation rate and good hydrophilicity, compression, resilience, and porosity than the non-crosslinked (NC) groups. The minimum inhibitory concentration (MIC) of AgNPs/GQDs presented some bactericidal effects against Gram-positive and Gram-negative bacteria. The cytotoxicity tests on bilayer scaffolds demonstrated good cell viability for human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Therefore, the Na-CMC bilayer scaffold could be a potential candidate for future diabetic wound care. Full article

Silk proteins have been highlighted in the past decade for tissue engineering (TE) and skin regeneration due to their biocompatibility, biodegradability, and exceptional mechanical properties. While silk fibroin (SF) has high structural and mechanical stability with high potential as an external protective layer, traditionally discarded sericin (SS) has shown great potential as a natural-based hydrogel, promoting cell–cell interactions, making it an ideal material for direct wound contact. In this context, the present study proposes a new wound dressing approach by developing an SS/SF bilayer construct for full-thickness exudative wounds. The processing methodology implemented included an innovation element and the cryopreservation of the SS intrinsic secondary structure, followed by rehydration to produce a hydrogel layer, which was integrated with a salt-leached SF scaffold to produce a bilayer structure. In addition, a sterilization protocol was developed using supercritical technology (sCO₂) to allow an industrial scale-up. The resulting bilayer material presented high porosity (>85%) and interconnectivity while promoting cell adhesion, proliferation, and infiltration of human dermal fibroblasts (HDFs). SS and SF exhibit distinct secondary structures, pore sizes, and swelling properties, opening new possibilities for dual-phased systems that accommodate the different needs of a wound during the healing process. The innovative SS hydrogel layer highlights the transformative potential of the proposed bilayer system for biomedical therapeutics and TE, offering insights into novel wound dressing fabrication. Full article