Injectable platelet-rich fibrin for perioral rejuvenation as assessed by 3D lip volume imaging.

BACKGROUND: Various injectable autologous platelet aggregate preparations have been developed and used for facial rejuvenation. Limited evidence exists for the use of these for augmentation of the lip. OBJECTIVES: This prospective, uncontrolled, single-center study evaluated the qualitative and quantitative effects of an injectable platelet-rich fibrin preparation (known as i-PRF+) for lip augmentation. PATIENTS/METHODS: PRF® PROCESS system technology was used to prepare i-PRF+ supernatant. Ten healthy females were included in the study and received a single intradermal injection of i-PRF+ in the upper and lower lips (5 ml in each quadrant, total ~2 ml). Participants were followed for 3 months post-procedure. The efficacy of the procedure was assessed qualitatively by a subjective patient-reported outcome (FACE-Q) assessment and quantitatively by objective 3D skin surface volume analysis (ProFace® ) at baseline and after 3 months. RESULTS: FACE-Q scales that measure satisfaction with skin and lip showed a statistically significant improvement from baseline (p = 0.04 and p = 0.02, respectively). Satisfaction with lip lines showed a numerical improvement with mean total scores for adverse effect scales related to the skin and lips reduced at 2 weeks post-procedure (p = 0.03 and p = 0.13, respectively). Overall lip volume at 3-month follow-up was unchanged (p = 0.11). The treatment was well tolerated with only minor adverse effects. CONCLUSIONS: A single session of i-PRF+ injections resulted in significant lip rejuvenation at 3-month follow-up, shown by improved patient-reported outcome measure. No significant change in lip volume was observed.

3D bioprinting of a stem cell-laden, multi-material tubular composite: An approach for spinal cord repair.

Development of a biomimetic tubular scaffold capable of recreating developmental neurogenesis using pluripotent stem cells offers a novel strategy for the repair of spinal cord tissues. Recent advances in 3D printing technology have facilitated biofabrication of complex biomimetic environments by precisely controlling the 3D arrangement of various acellular and cellular components (biomaterials, cells and growth factors). Here, we present a 3D printing method to fabricate a complex, patterned and embryoid body (EB)-laden tubular scaffold composed of polycaprolactone (PCL) and hydrogel (alginate or gelatine methacrylate (GelMA)). Our results revealed 3D printing of a strong, macro-porous PCL/hydrogel tubular scaffold with a high capacity to control the porosity of the PCL scaffold, wherein the maximum porosity in the PCL wall was 15%. The method was equally employed to create spatiotemporal protein concentration within the scaffold, demonstrating its ability to generate linear and opposite gradients of model molecules (fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) and rhodamine). 3D bioprinting of EBs-laden GelMA was introduced as a novel 3D printing strategy to incorporate EBs in a hydrogel matrix. Cell viability and proliferation were measured post-printing. Following the bioprinting of EBs-laden 5% GelMA hydrogel, neural differentiation of EBs was induced using 1 µM retinoic acid (RA). The differentiated EBs contained ßIII-tubulin positive neurons displaying axonal extensions and cells migration. Finally, 3D bioprinting of EBs-laden PCL/GelMA tubular scaffold successfully supported EBs neural differentiation and patterning in response to co-printing with 1 µM RA. 3D printing of a complex heterogeneous tubular scaffold that can encapsulate EBs, spatially controlled protein concentration and promote neuronal patterning will help in developing more biomimetic scaffolds capable of replicating the neural patterning which occurs during neural tube development.

Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations.

Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, with the clinician and clinical application site determining the precise needle gauge used for delivery. Here, we explored the role of needle diameter in microparticle delivery yield, and develop a modified viscosity formulation to improve microparticle delivery across a range of clinically relevant needle diameters. We have identified an optimal biocompatible formulation containing 0.25% pluronic F127 and 0.25% carboxymethyl cellulose, which can increase delivery payload to 520% across needle gauges 21-30G, and note that needle diameter impacts delivery efficacy. We use this formulation to increase the delivery yield of PLGA microparticles, and separately, PLGA-cell scaffolds supporting viable mesenchymal stem cells (MSCs), demonstrating the first in vitro delivery of this cell scaffold system. Together, these results highlight an optimal formulation for the delivery of microparticle and microparticle-cell scaffolds, and illustrate how careful choice of delivery formulation and needle size can dramatically impact delivery payload.

Release kinetics of prolyl hydroxylase inhibitors from collagen barrier membranes.

Collagen barrier membranes are used in guided tissue regeneration to support healing. This strategy, however, relies on the healing capacity of the tissue. Pharmacological inhibitors of prolyl hydroxylases can support regeneration by enhancing angiogenesis and are therefore a promising tool for periodontology. Here we evaluate the release kinetics of the prolyl hydroxylase inhibitors dimethyloxalylglycine and L-mimosine from collagen barrier membranes. Dimethyloxalylglycine and L-mimosine were lyophilized onto the collagen barrier membranes. The morphology of the collagen barrier membranes was analysed using scanning electron microscopy. The release of prolyl hydroxylase inhibitors was assessed by colorimetric and spectroscopic methods. Their ability to induce a cellular response was assessed in bioassays with gingival and periodontal ligament fibroblasts based on vascular endothelial growth factor production, proliferation, and metabolic activity of the cells. We found that loading of collagen barrier membranes with prolyl hydroxylase inhibitors did not change the overall membrane morphology. Assessment of the release kinetics by direct measurements and based on vascular endothelial growth factor production showed that supernatants obtained from the collagen barrier membranes in the first 6 hours had a sufficient level of prolyl hydroxylase inhibitors to induce vascular endothelial growth factor production. A similar kinetic was found when cell proliferation was assessed. Changes in metabolic activity did not reach the level of significance in the MTT assay. In conclusion, collagen barrier membranes can release prolyl hydroxylase inhibitors thereby increasing the pro-angiogenic capacity of periodontal cells in vitro. These findings provide the basis for preclinical studies to evaluate the regenerative capacity of prolyl hydroxylase inhibitors in periodontology and oral surgery.

Transcription factor STOX1A promotes mitotic entry by binding to the CCNB1 promotor.

BACKGROUND: In this study we investigated the involvement of the transcription factor STOX1A in the regulation of the cell cycle. METHODOLOGY/PRINCIPAL FINDINGS: We found that several major cell cycle regulatory genes were differentially expressed upon STOX1A stimulation and knockdown in the neuroblastoma cell line SH-SY5Y. This includes STOX1A dependent differential regulation of cyclin B1 expression, a cyclin which is known to regulate mitotic entry during the cell cycle. The differential regulation of cyclin B1 expression by STOX1A is direct as shown with chromatin immunoprecipitation. Results furthermore suggest that mitotic entry is enhanced through the direct upregulation of cyclin B1 expression effectuated by STOX1A. CONCLUSIONS: In conclusion we hereby show that STOX1A is directly involved in the regulation of the cell cycle.

Peritoneovenous shunt for treatment of intractable cirrhotic ascites: an unfulfilled promise?

Peritoneovenous shunt [PVS] is widely used for the treatment of cirrhotic ascites whether intractable ascites or not. Between February 996 and August 1998, PVSs were inserted in 22 patients [14 men and 8 women] with intractable cirrhotic ascites. The mean follow up period was 20 months. All patients were non-responsive to standard medical management. Nine patients were alive and palliated, seven of them with working shunts. Thirteen patients died within the first year, five of them died with non functioning shunts. Despite palliation, complications with PVSs were high and survival was limited. This modality was recommended only in patients with cirrhotic intractable ascites not responding to standard medical or surgical management