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Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes. Polymethylmethacrylate (PMMA) cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability. However, the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors. Here, we introduce porosity into PMMA cement by adding carboxymethylcellulose (CMC) to facilitate such local delivery of chemotherapeutic drugs, while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites. Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content. Upon incorporation of ≥3% CMC, the PMMA-based cements released up to 18% of the loaded cisplatin, in contrast to cements containing lower amounts of CMC which only released less than 2% of the cisplatin over 28 days. This release of cisplatin efficiently killed osteosarcoma cells in vitroand the fraction of dead cells increased to 91.3% at day 7, which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements. Additionally, tibias filled with PMMA-based cements containing up to 3% of CMC exhibit comparable compressive strengths as compared to intact tibias. In conclusion, we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels. As such, these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.

Bone defects resulting from trauma, surgery, congenital malformations, and other factors are among the most common health problems nowadays. Although current strategies such as autografts and allografts are recognized as the most successful treatments for stimulating bone regeneration, limitations such as graft source and complications still exist. SmartBone® is a xeno-hybrid bone graft (made from bovine bone matrix, poly(L-lactic-co-ε-caprolactone), and gelatin) with a positive clinical record for bone regeneration. In this study, the formulation for designing xeno-hybrid bone grafts using gelatins from different sources (bovine- and porcine-derived gelatin, with bone grafts named SBN and SPK, respectively) was investigated, and the biological responses were evaluated in vitroand in vivo. The results demonstrate that gelatins from both bovine and porcine sources can be loaded onto SmartBone® successfully and safely, withstanding the aggressive manufacturing processes. Different bone cell responses were observed in vitro. SBN was found to enhance osteocalcin secretion while SPK was found to upregulate osteopontin from human osteoblasts. In vivo, both bone grafts promoted osteogenesis, but SPK degraded earlier than SBN. Our findings suggest that SBN and SPK provide different yet comparable solutions for optimizing the bone resorption and regeneration balance. These xeno-hybrid bone grafts possess ideal potential for bone defect repairing.

Fine aggregate matrix (FAM) has been regarded as a key constituent of asphalt mixtures. Although several design methods have been recently proposed to prepare FAM specimens that represent the materials contained within the asphalt concretes, the volumetric characteristics of FAM may not be uniformly distributed within samples compacted using devices such as the Superpave gyratory compactor (SGC). This can mislead the mechanical analyses conducted with testing specimens that are typically extracted from different locations of the compacted samples, as they can present varying volumetric characteristics. This study employs the advanced micro-computed tomography (CT) scan technique to evaluate the air void distribution within FAM specimens extracted from different locations of SGC samples compacted with distinct air void contents. Rheological tests are performed in a dynamic shear rheometer to determine the dynamic shear modulus of the testing specimens. A statistical analysis is conducted to evaluate potential correlations between the volumetric and the rheological characteristics of the FAMs and to identify locations within the SGC samples from which small cylindrical specimens with similar characteristics can be extracted and used for testing. The adoption of advanced techniques such as the CT scan is essential for the advancement of the knowledge on the complex characteristics of asphalt mixtures, and may facilitate the fabrication of FAMs that are more representative of those that comprise asphalt concretes, as well as allow the use of similar replicates in mechanical tests.

Intra‐portal islet transplantation is currently the only clinically approved beta cell replacement therapy, but its outcome is hindered by limited cell survival due to a multifactorial reaction against the allogeneic tissue in liver. Adipose‐derived stromal cells (ASCs) can potentially improve the islet micro‐environment by their immunomodulatory action. The challenge is to combine both islets and ASCs in a relatively easy and consistent long‐term manner in a deliverable scaffold. Manufacturing the 3D bioprinted double‐layered scaffolds with primary islets and ASCs using a mix of alginate/nanofibrillated cellulose (NFC) bioink is reported. The diffusion properties of the bioink and the supportive effect of human ASCs on islet viability, glucose sensing, insulin secretion, and reducing the secretion of pro‐inflammatory cytokines are demonstrated. Diabetic mice transplanted with islet‐ASC scaffolds reach normoglycemia seven days post‐transplantation with no significant difference between this group and the group received islets under the kidney capsules. In addition, animals transplanted with islet‐ASC scaffolds stay normoglycemic and show elevated levels of C‐peptide compared to mice transplanted with islet‐only scaffolds. The data present a functional 3D bioprinted scaffold for islets and ASCs transplanted to the extrahepatic site and suggest a possible role of ASCs on improving the islet micro‐environment. Adipose‐derived stromal cells (ASCs) support survival and function of pancreatic islets in 3D bioprinted double‐layered alginate/nanocellulose‐based scaffold. Transplanting these scaffolds into the intraperitoneal site of a diabetic mouse model corrects diabetes seven days after transplantation with positive detection of C‐peptide from islets in scaffolds. This is accompanied with presence of ASCs in the scaffolds 60 days post‐transplantation.

The purpose of this study was to determine the degree of similarity between contralateral mandibular incisors utilising 3-dimensional (3D) models obtained from micro-computed tomographic (micro-CT) scans of extracted human teeth. The null hypothesis was that contralateral mandibular incisors do not exhibit matching symmetry.