Pervasive Induction of Regulatory Mutation Microclones in Sun-exposed Skin.

Carcinogen-induced mutations are thought near-random, with rare cancer-driver mutations underlying clonal expansion. Using high-fidelity Duplex Sequencing to reach a mutation frequency sensitivity of 4×10 per nt, we report that sun exposure creates pervasive mutations at sites with ∼100-fold UV-sensitivity in RNA-processing gene promoters - cyclobutane pyrimidine dimer (CPD) hyperhotspots - and these mutations have a mini-driver clonal expansion phenotype. Numerically, human skin harbored 10-fold more genuine mutations than previously reported, with neonatal skin containing 90,000 per cell; UV signature mutations increased 8,000-fold in sun-exposed skin, averaging 3×10 per nt.

Cyclobutane Pyrimidine Dimer Hyperhotspots as Sensitive Indicators of Keratinocyte UV Exposure.

The dominant DNA damage generated by UV exposure is the cyclobutane pyrimidine dimer (CPD), which alters skin cell physiology and induces cell death and mutation. Genome-wide nucleotide-resolution analysis of CPDs in melanocytes and fibroblasts has identified "CPD hyperhotspots", pyrimidine-pyrimidine sites hundreds of fold more susceptible to the generation of CPDs than the genomic average. Identifying hyperhotspots in keratinocytes could enable measuring individual past UV exposure in small skin samples and predicting future skin cancer risk.

Sequential growth factor exposure of human Ad-MSCs improves chondrogenic differentiation in an osteochondral biphasic implant.

Joint cartilage damage affects 10-12% of the world's population. Medical treatments improve the short-term quality of life of affected individuals but lack a long-term effect due to injury progression into fibrocartilage. The use of mesenchymal stem cells (MSCs) is one of the most promising strategies for tissue regeneration due to their ability to be isolated, expanded and differentiated into metabolically active chondrocytes to achieve long-term restoration.

A Cellularized Biphasic Implant Based on a Bioactive Silk Fibroin Promotes Integration and Tissue Organization during Osteochondral Defect Repair in a Porcine Model.

In cartilage tissue engineering, biphasic scaffolds (BSs) have been designed not only to influence the recapitulation of the osteochondral architecture but also to take advantage of the healing ability of bone, promoting the implant's integration with the surrounding tissue and then bone restoration and cartilage regeneration. This study reports the development and characterization of a BS based on the assembly of a cartilage phase constituted by fibroin biofunctionalyzed with a bovine cartilage matrix, cellularized with differentiated autologous pre-chondrocytes and well attached to a bone phase (decellularized bovine bone) to promote cartilage regeneration in a model of joint damage in pigs. BSs were assembled by fibroin crystallization with methanol, and the mechanical features and histological architectures were evaluated.

A Bioactive Cartilage Graft of IGF1-Transduced Adipose Mesenchymal Stem Cells Embedded in an Alginate/Bovine Cartilage Matrix Tridimensional Scaffold.

Articular cartilage injuries remain as a therapeutic challenge due to the limited regeneration potential of this tissue. Cartilage engineering grafts combining chondrogenic cells, scaffold materials, and microenvironmental factors are emerging as promissory alternatives. The design of an adequate scaffold resembling the physicochemical features of natural cartilage and able to support chondrogenesis in the implants is a crucial topic to solve.

Effect on growth and osteoblast mineralization of hydroxyapatite-zirconia (HA-ZrO) obtained by a new low temperature system.

Ceramics and bioceramics, such as hydroxyapatite and zirconium, are used in bone tissue engineering. Hydroxyapatite has chemical properties similar to bone while zirconium offers suitable mechanical properties. The aim of this article is to evaluate the ability to support cell growth and osteoblastic mineralization of hydroxyapatite-zirconium obtained by a new system based on different low temperatures, such as 873 K (HZ600), 923 K (HZ650) and 973 K (HZ700).

Using nanoinformatics methods for automatically identifying relevant nanotoxicology entities from the literature.

Nanoinformatics is an emerging research field that uses informatics techniques to collect, process, store, and retrieve data, information, and knowledge on nanoparticles, nanomaterials, and nanodevices and their potential applications in health care. In this paper, we have focused on the solutions that nanoinformatics can provide to facilitate nanotoxicology research. For this, we have taken a computational approach to automatically recognize and extract nanotoxicology-related entities from the scientific literature.