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.

Recent trends in bone tissue engineering: a review of materials, methods, and structures.

Bone tissue engineering provides the treatment possibility for segmental long bone defects that are currently an orthopedic dilemma. This review explains different strategies, from biological, material, and preparation points of view, such as using different stem cells, ceramics, and metals, and their corresponding properties for bone tissue engineering applications. In addition, factors such as porosity, surface chemistry, hydrophilicity and degradation behavior that affect scaffold success are introduced. Besides, the most widely used production methods that result in porous materials are discussed. Gene delivery and secretome-based therapies are also introduced as a new generation of therapies. This review outlines the positive results and important limitations remaining in the clinical application of novel bone tissue engineering materials and methods for segmental defects.

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.