Chemotherapy is the most used method after surgery in the treatment of colon cancer. Cancer cells escape the recognition mechanism of immune system cells to survive and develop chemoresistance. Therefore, the use of immunotherapy in combination with chemotherapy can increase the effectiveness of the treatment. Nanoparticles have been used clinically to increase the accumulation of therapeutics in target tissues and reduce toxicity. In this paper, nanoplexes were formed via cationic cyclodextrin polymer, 5-Fluorouracil, and Interleukin-2 based on the opposite charge interaction of macromolecules without undergoing any structural changes or losing the biological activity of Interleukin-2. Anticancer activities of nanoplexes were determined in two-dimensional and three-dimensional cell culture setups. The dual drug-loaded cyclodextrin nanoplexes diffused deeper into the spheroids and accelerated apoptosis when compared with 5-FU solutions. In the colorectal tumor-bearing animal model, survival rate, antitumor activity, metastasis, and immune response parameters were assessed using a cyclodextrin derivative, which was found to be safe based on the ALT/AST levels in healthy mice. Histomorphometric analysis showed that the groups treated with the nanoplex formulation had significantly fewer initial tumors and lung foci when compared with the control. The dual drug-loaded nanoplex could be a promising drug delivery technique in the immunochemotherapy of colorectal cancer.

Implant-related osteomyelitis (IRO) is recently controlled with local antibiotic delivery systems to overcome conventional therapy disadvantages. In vivo evaluation of such systems is however too little. We asked whether vancomycin (V)-containing poly-l-lactic acid/β-tricalcium phosphate (PLLA/β-TCP) composites control experimental IRO and promote bone healing in vivo. Fifty-six rats were distributed to five groups in this longitudinal controlled study. Experimental IRO was established at tibiae by injecting methicillin-resistant Staphylococcus aureus (MRSA) suspensions with titanium particles in 32 rats. Vancomycin-free PLLA/β-TCP composites were implanted into the normal and infected tibiae, whereas V-PLLA/β-TCP composites and coated (C)-V-PLLA/β-TCP composites were implanted into IRO sites. Sham-operated tibiae established the control group. Radiological and histological scores were quantified with microbiological findings on weeks 1 and 6. IRO is resolved in the CV- and the V-PLLA/β-TCP groups but not in the PLLA/β-TCP group. MRSA was not isolated in the CV- and the V-PLLA/β-TCP groups at all times whereas the bacteria were present in the PLLA/β-TCP group. Radiological signs secondary to infection are improved from 10.9 ± 0.9 to 3.0 ± 0.3 in the V-PLLA/β-TCP group but remained constant in the PLLA/β-TCP group. Histology scores are improved from 24.7 ± 6.5 to 17.6 ± 4.8 and from 27.6 ± 7.9 to 32.4 ± 8.9 in the CV-PLLA/β-TCP and the V-PLLA/β-TCP groups, respectively. New bone was formed in all the PLLA/β-TCP group at weeks 1 and 6. CV- and V-PLLA/β-TCP composites controlled experimental IRO and promoted bone healing. CV- and V-PLLA/β-TCP composites have the potential of controlling experimental IRO and promoting bone healing.

Bone spacers are exclusively used for replacing the tissue after trauma and/or diseases. Ceramic materials bring positive opportunities to enhance greater osteointegration and performance of implants, yet processing of porous geometries can be challenging. Additive Manufacturing (AM) opens opportunities to grade porosity levels in a part; however, its productivity may be low due to its batch processing approach. The paper studies the biological responses yielded by hydroxyapatite with β-TCP (tricalcium phosphate) ceramic porous bone spacers manufactured by robocasting 2-layer meshes that are rolled in green and sintered. The implants are assessed in vitro and in vivo for their compatibility. Human bone marrow mesenchymal stem cells attached, proliferated and differentiated on the bone spacers produced. Cells on the spacers presented alkaline phosphatase staining, confirming osteogenic differentiation. They also expressed bone-specific COL1A1, BGAP, BSP, and SPP1 genes. The fold change of these genes ranged between 8 to 16 folds compared to controls. When implanted into the subcutaneous tissue of rabbits, they triggered collagen fibre formation and mild fibroblastic proliferation. In conclusion, rolled AM-meshes bone spacers stimulated bone formation in vitro and were biocompatible in vivo. This technology may give the advantage to custom produce spacers at high production rates if industrially upscaled.