Nanostructured 3D-Printed Hybrid Scaffold Accelerates Bone Regeneration by Photointegrating Nanohydroxyapatite.

Nanostructured biomaterials that replicate natural bone architecture are expected to facilitate bone regeneration. Here, nanohydroxyapatite (nHAp) with vinyl surface modification is acquired by silicon-based coupling agent and photointegrated with methacrylic anhydride-modified gelatin to manufacture a chemically integrated 3D-printed hybrid bone scaffold (75.6 wt% solid content). This nanostructured procedure significantly increases its storage modulus by 19.43-fold (79.2 kPa) to construct a more stable mechanical structure. Furthermore, biofunctional hydrogel with biomimetic extracellular matrix is anchored onto the filament of 3D-printed hybrid scaffold (HGel-g-nHAp) by polyphenol-mediated multiple chemical reactions, which contributes to initiate early osteogenesis and angiogenesis by recruiting endogenous stem cells in situ. Significant ectopic mineral deposition is also observed in subcutaneously implanted nude mice with storage modulus enhancement of 25.3-fold after 30 days. Meanwhile, HGel-g-nHAp realizes substantial bone reconstruction in the rabbit cranial defect model, achieving 61.3% breaking load strength and 73.1% bone volume fractions in comparison to natural cranium 15 weeks after implantation. This optical integration strategy of vinyl modified nHAp provides a prospective structural design for regenerative 3D-printed bone scaffold.

Bioinspired Hydrogel Anchoring 3DP GelMA/HAp Scaffolds Accelerates Bone Reconstruction.

Seeking high biological activity and osteoinductive ability has always been an urgent problem for three-dimensional-printed (3DP) bony implants. Here, a 3DP methacrylic anhydride-modified gelatin (GelMA)/hydroxyapatite (HAp) scaffold with a high solid content of 82.5% was prepared and anchored by a functionalized polyphenol hydrogel. The scaffold and hydrogel were organically integrated into a bioinspired bony implant (HGH) by phenolic hydroxyl of hyaluronan derivatives conjugating amino groups of collagen I and GelMA and further chelating calcium ions of HAp. Compared with a simplex 3DP scaffold, this freeze-dried HGH presented better water retention, delayed degradation, and mechanical stability. It could promote migration, proliferation, and osteogenic differentiation of bone marrow stem cells in vitro. One week of implantation showed that it promoted directional migration of endogenous stem cells and early osteogenesis and angiogenesis. After 15 week surgery of rabbit skull defects, the BV/TV value of HGH returned to 73% of the normal group level. This strategy provided a new research idea for bone regeneration.

Evolutionary dynamics of cancer multidrug resistance in response to olaparib and photodynamic therapy.

P-glycoprotein (P-gp) is an adenosine triphosphate (ATP)-dependent drug efflux protein commonly associated with multidrug resistance in cancer chemotherapy. In this report, we used a dual-fluorescent co-culture model to study the population dynamics of the drug sensitive human ovarian cancer cell line (OVCAR-8-DsRed2) and its resistant subline that overexpresses P-gp (NCI/ADR-RES-EGFP) during the course of a photodynamic therapy (PDT)-olaparib combination regimen. Without treatment, OVCAR-8-DsRed2 cells grew more rapidly than the NCI/ADR-RES-EGFP cells. Olaparib treatment reduced the total number of cancer cells by 70±4% but selected for the resistant NCI/ADR-RES-EGFP population since olaparib is an efflux substrate for the P-gp pump. This study used the FDA-approved benzoporphyrin derivative (BPD) photosensitizer or its lipidated formulation ((16:0)LysoPC-BPD) to kill OVCAR-8 cells and reduce the likelihood that olaparib-resistant cells would have selective advantage. Three cycles of PDT effectively reduced the total cell number by 66±3%, while stabilizing the population ratio of sensitive and resistant cells at approximately 1:1. The combination of olaparib treatment and PDT enhanced PARP cleavage and deoxyribonucleic acid (DNA) damage, further decreasing the total cancer cell number down to 10±2%. We also showed that the combination of olaparib and (16:0)LysoPC-BPD-based PDT is up to 18-fold more effective in mitigating the selection of resistant NCI/ADR-RES-EGFP cells, compared to using olaparib and BPD-based PDT. These studies suggest that PDT may improve the effectiveness of olaparib, and the use of a lipidated photosensitizer formulation holds promise in overcoming cancer drug resistance.

Determination of the Contents of Antioxidants and Their Degradation Products in Sodium Chloride Injection for Blood Transfusion.

The infusion bag is mainly made up of polyolefin polymer. Antioxidants are usually added to these polymer materials in the production process to prevent the materials from aging and enhance the stability of the materials. Because of the potential harm of antioxidants to human body, it is necessary to limit the amount of antioxidants migrating to the pharmaceutical solutions. In the present study, we developed and validated the HPLC method for the simultaneous quantification of antioxidants and their degradation products migrating to sodium chloride solution for injection. A total of six antioxidants and six their degradation products were separated and simultaneously determined by using a Waters Symmetry RP18 column (250 × 4.6 mm, 5 µm) and gradient elution of methanol/acetonitrile/acetic acid-water (1 : 99, v/v) at a flow rate of 1.0 mL/min. The detective wavelength was set at 277 nm, and the column temperature was maintained at 35°C. The method was validated in terms of limit of detection (LOD, 0.011-0.151 µg/mL), limit of quantification (LOQ, 0.031-0.393 µg/mL), intraday precision (0.25%-3.17%), interday precision (0.47%-3.48%), linearity (0.1-46.8 µg/mL, r > 0.9994), stability (0.35%-3.29%), and accuracy (80.39%-104.31%). In the extraction experiment, antioxidants, BHT, 1010, 1330, 1076, and 168, and their degradation products, 1310 and DBP, were detected in the packaging materials. Only 1310 was detected in the migration experiment. The maximum daily dosage of sodium chloride for blood transfusion is three bags, and the content of 1310 in long-term testing samples is from 0 to 12 months ranging from 37.44 µg/3 bags to 48.71 µg/3 bags. The daily intake of 1310 did not exceed 48.71 µg, which was much lower than its permitted daily exposure (PDE, 300 µg/day). Therefore, the antioxidants and their degradation products migrating into the drug solution would not cause drug safety risks.