A comprehensive bench-to-bed look into the application of gamma-sterilized 3D-printed polycaprolactone/hydroxyapatite implants for craniomaxillofacial defects, an in vitro, in vivo, and clinical study.

This study investigates the safety and efficacy of 3D-printed polycaprolactone/hydroxyapatite (PCL/HA) scaffolds for patient-specific cranioplasty surgeries, employing liquid deposition modeling (LDM) technology. This research is pioneering as it explores the impact of gamma radiation on PCL/HA scaffolds and utilizes printing ink with the highest content of HA known in the composite. The mechanical, morphological, and macromolecular stability of the gamma-sterilized scaffolds were verified before implantation. Subsequent research involving animal subjects was conducted to explore the effects of sterilized implants. Eventually, three clinical cases were selected for the implantation studies as part of a phase 1 non-randomized open-label clinical trial. It was shown that a 25 kGy gamma-ray dose for sterilizing the printed implants did not alter the required geometrical precision of the printed implants. The implants exhibited well-distributed HA and strength comparable to cancellous bone. Gamma radiation reduced hydrophobicity and water uptake capacity without inducing pyrogenic or inflammatory responses. Personalized PCL/HA substitutes successfully treated various craniomaxillofacial defects, including trauma-induced facial asymmetry and congenital deformities. HA nanoparticles in the ink stimulated significant osteoconductive responses within three months of implantation. Moreover, the results revealed that while larger implants may exhibit a slower bone formation response in comparison to smaller implants, they generally had an acceptable rate and volume of bone formation. This clinical trial suggests the application of a sterilized PCL/HA composite for craniomaxillofacial surgery is safe and could be considered as a substitute for autologous bone.

An in vitro and in vivo study of electrospun polyvinyl alcohol/chitosan/sildenafil citrate mat on 3D-printed polycaprolactone membrane as a double layer wound dressing.

Double-layer dermal substitutes (DS) generally provide more effective therapeutic outcomes than single-layer substitutes. The architectural design of DS incorporates an outer layer to protect against bacterial invasions and maintain wound hydration, thereby reducing the risk of infection and the frequency of dressing changes. Moreover, the outer layer is a mechanical support for the wound, preventing undue tension in the affected area. A 3D-printed polycaprolactone (PCL) membrane was utilized as the outer layer to fabricate DS wound dressing. Simultaneously, a polyvinyl alcohol/chitosan/sildenafil citrate (PVA/CS/SC) scaffold was electrospun onto the PCL membrane to facilitate cellular adhesion and proliferation. Scanning electron microscopy (SEM) analysis of the PCL filaments revealed a consistent cross-sectional surface and structure, with an average diameter of 562.72 ±â€¯29.15 µm. SEM results also demonstrated uniform morphology and beadless structure for the PVA/CS/SC scaffold, with an average fiber diameter of 366.77 ±â€¯1.81 nm for PVA/CS. The addition of SC led to an increase in fiber diameter while resulting in a reduction in tensile strength. However, drug release analysis indicated that the SC release from the sample can last up to 72 h. Animal experimentation confirmed that DS wound dressing positively accelerated wound closure and collagen deposition in the Wistar rat skin wound model.

Microfluidic System Consisting of a Magnetic 3D-Printed Microchannel Filter for Isolation and Enrichment of Circulating Tumor Cells Targeted by Anti-HER2/MOF@Ferrite Core-Shell Nanostructures: A Theranostic CTC Dialysis System.

Low number of circulating tumor cells (CTCs) in the blood samples and time-consuming properties of the current CTC isolation methods for processing a small volume of blood are the biggest obstacles to CTC usage in practice. Therefore, we aimed to design a CTC dialysis system with the ability to process cancer patients' whole blood within a reasonable time. Two strategies were employed for developing this dialysis setup, including (i) synthesizing novel in situ core-shell Cu ferrites consisting of the Cu-CuFe2O4 core and the MIL-88A shell, which are targeted by the anti-HER2 antibody for the efficient targeting and trapping of CTCs; and (ii) fabricating a microfluidic system containing a three-dimensional (3D)-printed microchannel filter composed of a polycaprolactone/Fe3O4 nanoparticle composite with pore diameter less than 200 µm on which a high-voltage magnetic field is focused to enrich and isolate the magnetic nanoparticle-targeted CTCs from a large volume of blood. The system was assessed in different aspects including capturing the efficacy of the magnetic nanoparticles, CTC enrichment and isolation from large volumes of human blood, side effects on blood cells, and the viability of CTCs after isolation for further analysis. Under the optimized conditions, the CTC dialysis system exhibited more than 80% efficacy in the isolation of CTCs from blood samples. The isolated CTCs were viable and were able to proliferate. Moreover, the CTC dialysis system was safe and did not cause side effects on normal blood cells. Taken together, the designed CTC dialysis system can process a high volume of blood for efficient dual diagnostic and therapeutic purposes.

Evaluation of the Morphological Effects of Hydroxyapatite Nanoparticles on the Rheological Properties and Printability of Hydroxyapatite/Polycaprolactone Nanocomposite Inks and Final Scaffold Features.

This study is focused on the importance of nanohydroxyapatite (nHA) particle morphology with the same particle size range on the rheological behavior of polycaprolactone (PCL) composite ink with nHA as a promising candidate for additive manufacturing technologies. Two different physiologic-like nHA morphologies, that is, plate and rod shape, with particles size less than 100 nm were used. nHA powders were well characterized and the printing inks were prepared by adding the different ratios of nHA powders to 50% w/v of PCL solution (nHA/PCL: 35/65, 45/55, 55/45, and 65/35 w/w%). Subsequently, the influence of nHA particle morphology and concentration on the printability and rheological properties of composite inks was investigated. HA nanopowder analysis revealed significant differences in their microstructural properties, which affected remarkably the composite ink printability in several ways. For instance, adding up to 65% w/w of plate-like nHA to the PCL solution was possible, while nanorod HA could not be added above 45% w/w. The printed constructs were successfully fabricated using the extrusion-based printing method and had a porous structure with interconnected pores. Total porosity and surface area increased with nHA content due to the improved fiber stability following deposition of material ink. Consequently, degradation rate and bioactivity increased, while compressive properties decreased. While nanorod HA particles had a more significant impact on the mechanical strength than plate-like morphology, the latter showed less crystalline order, which makes them more bioactive than nanorod HA. It is therefore important to note that the nHA microstructure broadly affects the printability of printing ink and should be considered according to the intended biomedical applications.

Bioprinted Membranes for Corneal Tissue Engineering: A Review.

Corneal transplantation is considered a convenient strategy for various types of corneal disease needs. Even though it has been applied as a suitable solution for most corneal disorders, patients still face several issues due to a lack of healthy donor corneas, and rejection is another unknown risk of corneal transplant tissue. Corneal tissue engineering (CTE) has gained significant consideration as an efficient approach to developing tissue-engineered scaffolds for corneal healing and regeneration. Several approaches are tested to develop a substrate with equal transmittance and mechanical properties to improve the regeneration of cornea tissue. In this regard, bioprinted scaffolds have recently received sufficient attention in simulating corneal structure, owing to their spectacular spatial control which produces a three-cell-loaded-dimensional corneal structure. In this review, the anatomy and function of different layers of corneal tissue are highlighted, and then the potential of the 3D bioprinting technique for promoting corneal regeneration is also discussed.

An in vitro and in vivo study of PCL/chitosan electrospun mat on polyurethane/propolis foam as a bilayer wound dressing.

In the current study, we fabricated a bilayer wound dressing consisting of an electrospun poly-ε-caprolactone/chitosan (PCL/CS) fibrous mat as the sublayer and a polyurethane (PU) foam coated with ethanolic extract of propolis (EEP) as the top layer. By blending the solutions of PCL and CS, we fabricated an electrospun mat consisting of bead-free and uniform nanofibers with enhanced hydrophilicity, swelling ratio, and degradation properties. To further enhance the mechanical and antibacterial properties, we electrospun the PCL/CS solution on a PU foam coated with EEP to fabricate the PCL/CS-PU/EEP bilayer wound dressing. Furthermore, the PCL/CS-PU/EEP bilayer wound dressing demonstrated enhanced cell compatibility and healing properties through in vitro and in vivo studies. Therefore, the PCL/CS-PU/EEP bilayer wound dressing offers great potential to be used as a wound dressing because of its suitable mechanical properties, swelling profile, antibacterial activity, biocompatibility, and wound healing properties.

Synthesis and characterization of a laminated hydroxyapatite/gelatin nanocomposite scaffold with controlled pore structure for bone tissue engineering.

In this study, a nanostructured scaffold was designed for bone repair using hydroxyapatite (HA) and gelatin (GEL) as its main components. Nanopowders of HA were synthesized, and together with GEL, used to engineer a 3-dimensional nanocomposite combining 3 techniques of layer solvent casting, freeze-drying, and lamination. The results show that the scaffold possesses a 3-dimensional interconnected homogenous porous structure with a porosity of 82% and pore sizes ranging from 300 to 500 mum. It has also been shown that mechanical indices are in the range of spongy bones. Cultured osteoblast-like cells (SaOS-2) have shown an excellent level of cell attachment, migration, and penetration into the porosities of the nanocomposite scaffold. Here, we have shown that by a combination of widely available methods with simple experimental operations, nano-HA powders can be synthesized and used to make 3-dimensional HA/GEL nanocomposites in any desired shape, with mechanical properties comparable to spongy bone.