Nanocomposite Hydrogel Produced from PEGDA and Laponite for Bone Regeneration.

Herein, a nanocomposite hydrogel was produced using laponite and polyethylene-glycol diacrylate (PEGDA), with or without Irgacure (IG), for application in bone tissue regeneration. The nanocomposites were characterized by X-ray diffraction (XRD), Fourier-Transform infrared spectroscopy (FTIR), and thermal analysis (TG/DTG). The XRD results showed that the crystallographic structure of laponite was preserved in the nanocomposite hydrogels after the incorporation of PEGDA and IG. The FTIR results indicated that PEGDA polymer chains were entangled on laponite in hydrogels. The TG/DTG found that the presence of laponite (Lap) improved the thermal stability of nanocomposite hydrogel. The toxicity tests by Artemia salina indicated that the nanocomposite hydrogels were not toxic, because the amount of live nauplii was 80.0%. In addition, in vivo tests demonstrated that the hydrogels had the ability to regenerate bone in a bone defect model of the tibiae of osteopenic rats. For the nanocomposite hydrogel (PEGDA + Lap nanocomposites + UV light), the formation of intramembranous bone in the soft callus was more intense in 66.7% of the animals. Thus, the results presented in this study evidence that nanocomposite hydrogels obtained from laponite and PEGDA have the potential for use in bone regeneration.

Biomineralization inspired engineering of nanobiomaterials promoting bone repair.

A biomineralization processes is disclosed for engineering nanomaterials that support bone repair. The material was fabricated through a hot press process using electrospun poly(lactic acid) (PLA) matrix covered with hybrid composites of carbon nanotubes/graphene nanoribbons (GNR) and nanohydroxyapatite (nHA). Various scaffolds were devised [nHA/PLA, PLA/GNR, and PLA/nHA/GNR (1 and 3%)] and their structure and morphology characterized through Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDS), and Atomic force microscope (AFM). Moreover, thorough biocompatibility and toxicity studies were performed. Here, in vivo studies on toxicity and cytotoxicity were conducted in aqueous dispersions of the biomaterials at concentrations of 30, 60, and 120 µg/mL using the Allium cepa test. Further toxicity studies were performed through hemolysis toxicity tests and genotoxicity tests evaluating the damage index and damage frequencies of DNAs through comet assays with samples of the animals' peripheral blood, marrow, and liver. Additionally, the regenerative activity of the scaffolds was analyzed by measuring the cortical tibiae of rats oophorectomized implanted with the biomaterials. Biochemical analyzes [glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), urea, calcium, phosphorus, and alkaline phosphatase (ALP)] were also performed on blood samples. The results suggested a toxicity and cytotoxicity level for the GNR biomaterials at a concentration of 60 and 120 µg/mL, but non-toxicity and cytotoxicity for the 30 µg/mL concentration. The scaffolds obtained at a concentration of 0.3 mg/cm2 were not toxic in the hemolysis test and demonstrated no cytotoxicity, genotoxicity, and mutagenicity in the blood, marrow, and liver analyzes of the animals, corroborating data from the biochemical markers of GPT, GOT, and urea. Tissue regeneration was performed in all groups and was more pronounced in the group containing the combination of nHA/GNR (3%), which is consistent with the data obtained for the calcium, serum phosphorus, and ALP concentrations. Consequently, the study indicates that the engineered nanobiomaterial is a promising candidate for bone tissue repair and regenerative applications. STATEMENT OF SIGNIFICANCE: The scientific contribution of this study is the engineering of a synthetic hybrid biomaterial, in nanoscale by a pressing and heating process. A biodegradable polymeric matrix was covered on both sides with a carbonated hybrid bioceramic/graphene nanoribbons (GNR), which has hydrophilic characteristics, with chemical elements stoichiometrically similar to bone mineral composition. The nanomaterial displayed promising bone regeneration ability, which is the first example to be used in an osteoporotic animal model. Moreover, detailed biocompatibility and toxicity studies were performed on the nanomaterials and their compositions, which is of great interest for the scientific community.

Bioprinting a Synthetic Smectic Clay for Orthopedic Applications.

Bioprinting technology has emerged as an important approach to bone and cartilage tissue engineering applications, because it allows the printing of scaffolds loaded with various components, such as cells, growth factors, or drugs. In this context, the bone has a very complex architecture containing highly vascularized and calcified tissues, while cartilage is avascular and has low cellularity and few nutrients. Owing to this complexity, the repair and regeneration of these tissues are highly challenging. Identification of the appropriate biomaterial and fabrication technologies can provide sustainable solutions to this challenge. Here, nanosized Laponite® (Laponite is a trademark of the company BYK Additives Ltd.) has shown to be a promising material due to its unique properties such as excellent biocompatibility, facile gel formation, shear-thinning property (reversible physical crosslinking), high specific surface area, degrade into nontoxic products, and with osteoinductive properties. Even though Laponite and Laponite-based composite for 3D bioprinting application are considered as soft gels, they may therefore not be thought exhibiting sufficient mechanical strength for orthopedic applications. However, through the merging with suitable composite and, also by incorporation of crosslinking step, desired mechanical strength for orthopedic application can be obtained. In this review, recent advances and future perspective of bioprinting Laponite and Laponite composites for orthopedic applications are highlighted.

Electrospun Nanofibrous Poly (Lactic Acid)/Titanium Dioxide Nanocomposite Membranes for Cutaneous Scar Minimization.

Poly (lactic acid) (PLA) has been increasingly used in cutaneous tissue engineering due to its low cost, ease of handling, biodegradability, and biocompatibility, as well as its ability to form composites. However, these polymers possess a structure with nanoporous that mimic the cellular environment. In this study, nanocomposites are prepared using PLA and titanium dioxide (TiO2) (10 and 35%-w/w) nanoparticles that also function as an active anti-scarring agent. The nanocomposites were prepared using an electrospinning technique. Three different solutions were prepared as follows: PLA, 10% PLA/TiO2, and 35% PLA/TiO2 (w/w%). Electrospun PLA and PLA/TiO2 nanocomposites were characterized morphologically, structurally, and chemically using electron scanning microscopy, transmission electron microscopy, goniometry, and X-ray diffraction. L929 fibroblast cells were used for in vitro tests. The cytotoxic effect was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Versicam (VCAN), biglicam (BIG), interleukin-6 (IL6), interleukin-10 (IL-10), and type-1 collagen (COL1A1) genes were evaluated by RT-qPCR. In vivo tests using Wistar rats were conducted for up to 15 days. Nanofibrous fibers were obtained for all groups that did not contain residual solvents. No cytotoxic effects were observed for up to 168 h. The genes expressed showed the highest values of versican and collagen-1 (p < 0.05) for PLA/TiO2 nanocomposite scaffolds when compared to the control group (cells). Histological images showed that PLA at 10 and 35% w/w led to a discrete inflammatory infiltration and expression of many newly formed vessels, indicating increased metabolic activity of this tissue. To summarize, this study supported the potential of PLA/TiO2 nanocomposites ability to reduce cutaneous scarring in scaffolds.