Versatile cell cultivation on injectable poly(butylene adipate-co-terephthalate) microcarriers: Impact of surface properties across different cell types.

Injectable cell therapies offer several advantages compared with traditional open surgery, including less trauma to the patient, shorter recovery time, and lower risk of infection. However, a significant problem is the difficulty in developing effective cell delivery carriers that are cyto-compatible and maintain cell viability both during and after injection. In the presented study, it was aimed to develop poly(butylene adipate-co-terephthalate) (PBAT) microcarriers using the emulsion preparation-solvent evaporation technique. The optimized diameter of the PBAT microcarriers was determined as 104 ± 15 µm at 700 rpm and there would be no blockage after injection due to the nonswelling feature of microcarriers. Furthermore, the cellular activities of PBAT microcarriers were evaluated in static culture for 7 days using L929 mouse fibroblasts, MC3T3-E1 mouse pre-osteoblasts, and rat adipose-derived mesenchymal cells (AdMSCs). 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide results and Sscanning electron microscope images showed that PBAT microcarriers increased the adhesion and proliferation properties of pre-osteoblasts and stem cells, while L929 fibroblasts formed aggregates by adhering to certain regions of the microcarrier surface and did not spread on the surface. These results emphasize that PBAT microcarriers can be used as injectable carriers, especially in stem cell therapies, but their surface properties need to be modified for some cells.

Effect of a musical toy used during peripheral venous access on children's pain, fear and parental satisfaction: Randomized controlled trial.

PURPOSE: This research was completed to determine the effect of a musical toy (xylophone) on pain and fear in children and parental satisfaction during peripheral venous access in children. DESIGN AND METHODS: This research was completed as a randomized controlled trial study. The sample for the research comprised 70 children (control: 35, experiment: 35) aged 3-6 years with peripheral venous access who were admitted to the Pediatric ward and their parents abiding with case selection criteria. RESULTS: The mean Children's Emotional Manifestation Scale score for children in the experiment group was found to be statistically significantly lower than in the control group (p < 0.05). Children in the experiment group had statistically significantly different mean Children's Fear Scale scores, which were found to be low (p < 0.05). No statistically significant difference was found between the pain scores of the experimental and control groups (p > 0.05). There was a statistically significant difference present for patient cooperation with the nurse in the experiment group (p < 0.05). CONCLUSION: Though the use of a musical toy during the peripheral venous access procedure had positive impacts on fear and emotional symptoms in the child, it did not appear to have any effect on the child's pain level or parental satisfaction. PRACTICE IMPLICATIONS: The use of a xylophone during painful procedures performed on children is recommended in terms of reducing the negative impact of the procedure on children by ensuring the child and parent focus on each other during the procedure and the parent contributes to care.

Polymer-clay nanofibrous wound dressing materials containing different boron compounds.

BACKGROUND: Montmorillonite (MMT) is a biocompatible nanoclay and its incorporation into polymeric matrix not only improves the polymer's wettability/biodegradability, but also enhances cellular proliferation, and differentiation. On the other hand, the positive effect of boron (B) on the healing cascade and its antibacterial properties have drawn the attention of researchers. MATERIALS & METHODS: In this regard, B compounds in different chemical structures, boron nitride (BN), zinc borate (ZB), and phenylboronic acid (PBA), were adsorbed onto MMT and then, poly (lactic acid) (PLA) based MMT/B including micron/submicron fibers were fabricated by electrospinning. RESULTS: The incorporation of MMT nanoparticles into the PLA demonstrated a porous fiber topography with enhanced thermal properties, water uptake capacity, and antibacterial effect. Furthermore, the composites including BN, ZB, and PBA showed bacteriostatic effects against Gram-negative and Gram-positive pathogenic bacteria (Escherichia coli and Staphylococcus aureus). In-vitro cell culture studies performed with human dermal fibroblasts (HDF) indicated the non-toxic effect of B compounds. The results showed that incorporation of MMT supported cell adhesion and proliferation, and further addition of B compounds especially PBA increased cell viability for 14 days. CONCLUSION: The results illustrated the acceptable characteristics of the B-containing composites and their favorable effect on the cells, demonstrating their potential as a skin tissue engineering product.

Organomodified nanoclay with boron compounds is improving structural and antibacterial properties of nanofibrous matrices.

In this study, nanofibrous polymeric matrices were successfully developed with nanoclay, montmorillonite (MMT) and various boron (B) compounds, which were known to have positive effects on the wound healing with elevated antibacterial properties. For this purpose, MMT was modified with quaternary ammonium salt, trimethyl octadecyl ammonium bromide (TMOD), and boron compounds, boron nitride (BN), zinc borate (ZB), or phenylboronic acid (PBA) were adsorbed on organomodified MMT (OMMT). Then, poly (lactic acid) (PLA) based nanofibrous PLA-OMMT/B composites were fabricated via electrospinning. Modification of MMT nanoparticles with TMOD occurred through ion-exchange reaction and led to better homogenous fibrous structures which exhibited dramatic inhibition for gram-positive bacteria. Moreover, composites with ZB and PBA demonstrated both bacteriostatic and bactericidal effects for gram-positive and gram-negative bacteria. The chemical structures of the matrices were evaluated through ATR-FTIR and supported the intercalated composite formation. The thermal and mechanical stabilities of PLA matrices were also enhanced after OMMT and B incorporation. The lowest breaking strain value was recorded for PLA-OMMT/PBA composite compared to other B composites. The 100% and 50% extracts of the PLA-OMMT matrices showed modest cytotoxic effect on the human dermal fibroblasts (NHDF) on the second day culture that probably originated from TMOD. These results demonstrated that PLA-OMMT/B matrices, especially PBA including matrices, can be used as replaceable wound dressings that have limited interaction with cells but exhibit antibacterial activity and support the early stages of wound healing both morphologically and chemically.

Biological nerve conduit model with de-epithelialized human amniotic membrane and adipose-derived mesenchymal stem cell sheet for repair of peripheral nerve defects.

In this study, a biological conduit, consisting of an adipocyte-derived mesenchymal stem cell (AdMSCs) sheet and amniotic membrane (AM), was designed for the reconstruction of peripheral nerve defects. To evaluate the effect of the produced conduit on neural regeneration, a 10-mm sciatic nerve defect was created in rats, and experiments were carried out on six groups, i.e., sham control group (SC), negative control group (NC), nerve autograft group (NG), the biological conduit (AdMSCs + AM) group, the commercial PGA tube conduit (PGA) group, and the conduit only consisting of AM (AM) group. The effects of different nerve repair methods on the peripheral nerve and gastrocnemius muscle were evaluated by functional, histological, and immunohistochemical tests. When the number of myelinated axons was compared between the groups of AdMSCs + AM and PGA, it was higher in the AdMSCs + AM group (p < 0.05). The percentage of gastrocnemius collagen bundle area of AdMSCs + AM group was found to be statistically lower than the PGA group (p < 0.05). The muscle fiber diameter of AdMSCs + AM group was lower than that of the NG group, but significantly higher than that of the PGA group and the AM group (p < 0.001). Muscle weight index was significantly higher in the AdMSCs + AM group compared to the PGA group (p < 0.05). It was observed that nerve regeneration was faster in the AdMSCs + AM group, and there was an earlier improvement in pin-prick score and sciatic functional index compared to the PGA group and the AM group. In conclusion, the biological conduit prepared from the AdMSCs sheet and AM is regarded as a new biological conduit that can be used as an alternative treatment method to nerve autograft in clinical applications.

Comparison of Cytokine Hemadsorption as an Immunomodulator Therapy in COVID-19 Patients with and without Bacterial Sepsis.

BACKGROUND: In this retrospective study, we aimed to compare the laboratory and clinical results of cytokine hem-adsorption as an immunomodulation therapy in COVID-19 ICU patients with or without sepsis. METHODS: The levels of PCT, CRP, and ferritin were determined as indicators of infection/sepsis; the levels of in-terleukins (IL-6, IL-8 and IL-10, and TNF-α) were determined as indicators of cytokine storm were compared. APACHE score, SOFA score, and mortality rates were compared for the progression of the disease in 23 COVID-19 patients. RESULTS: The therapy was generally successful in reducing the levels of IL-6, IL-8, IL-10, and TNF-α but the levels measured after the procedure did not differ among the patients with or without sepsis, suggesting that the presence of sepsis did not affect the efficacy and function of the cytokine hemadsorption procedure in COVID-19 patients. All parameters were reduced after the procedure except the levels of PCT and ferritin and mortality rates of patients diagnosed with sepsis. The level of PCT was significantly higher in these patients compared with the patients without sepsis while the ferritin and mortality did not show any significant difference between the two groups, suggesting that the cytokine hemadsorption may be safe in the treatment of critical COVID-19 patients. CONCLUSIONS: As a result, the progression of sepsis in COVID-19 may be avoided with cytokine hemadsorption applied as an immunomodulator therapy. However, this therapy should be further explored and validated prior to its introduction to everyday clinical practice when the epidemic conditions end.

Investigation of the synergistic effect of platelet-rich plasma and polychromatic light on human dermal fibroblasts seeded chitosan/gelatin scaffolds for wound healing.

Conventional wound healing treatments are insufficient for chronic wounds caused by factors such as senescence of fibroblasts, reduced growth factor synthesis, and poor angiogenesis. Recently, tissue engineering approaches have been investigated to develop effective therapies. In this study, a biochemical/biophysical stimulant-based 3D system was developed for the healing of chronic wounds. In this direction, genipin crosslinked chitosan (CHT)/gelatin (GEL) scaffolds were fabricated by freeze-drying and loaded with platelet-rich plasma (PRP). The scaffolds were seeded with human dermal fibroblasts and then, polychromatic light in near infrared region (NIR) was applied to the scaffolds for activating the platelets and stimulating the fibroblasts (photoactivation, PAC). Thus, fibroblasts were stimulated both chemically and physically by PRP and light, respectively. Cell migration, proliferation, morphology, gene expressions and reactive oxygen species (ROS) activity were evaluated in-vitro. Laminin and collagen 4 expressions that are important for extracellular matrix (ECM) formation, and PDGF (Platelet-derived growth factor) and VEGF (Vascular endothelial growth factor) expressions that are important for vascularization significantly increased in the presence of both PRP and light. Besides, PRP and light improved cell migration in 3D core-and shell model synergistically. Hydrogen peroxide content decreased in both PRP and light, indicating inhibition of ROS production. It was concluded that the stimulation of platelets with light in the NIR has a great potential to use for both platelets activation and stimulation of fibroblasts. As a result, an effective therapy can be developed for chronic wounds by using scaffold-based 3D systems together with PRP and photostimulation.

Three dimensional nanofibrous and compressible poly(L-lactic acid) bone grafts loaded with platelet-rich plasma.

In this study, nanofibrous matrices of poly(L-lactic acid)-hydroxyapatite (PLLA-HAp) were successfully fabricated by three-dimensional (3D) electrospinning for use in the treatment of irregular bone damages. Compressibility analysis showed that 3D nanofibrous grafts occupied at least 2-fold more volume than their 2D form and they can easily take shape of the defect zone with irregular geometry. Moreover, the compression moduli of the PLLA and PLLA-HAp grafts were calculated as 8.0 ± 3.0 kPa and 11.8 ± 3.9 kPa, respectively, while the strain values of the same samples at the maximum load of 600 kPa were 164 ± 28% and 130 ± 20%, respectively. Treatment of the grafts with aqueous sodium hydroxide solution increased the surface roughness and thus the alloplastic graft materials (PLLA-HAp/M) protecting the fiber morphology were produced successfully. Then, platelet-rich plasma (PRP) was loaded into the surface modified grafts and activated with 10% calcium chloride. The efficiency of the activation was evaluated with flow cytometry and it was found that after activation the percentages of CD62 (P-selectin) and CD41/61 (glycoprotein IIb/IIIa) proteins increased approximately 4-fold. Surface hydrophilicity and biological activity of the PLLA-HAp grafts were enhanced by fibrin coating after PRP activation. Thein vitrocell culture studies which were carried out by using mouse pre-osteoblasts (MC3T3-E1) showed that graft materials supported by PRP increased cellular proliferation and osteogenic differentiation significantly. Thein vivoresults demonstrated that compared with bare PLLA-HAp/M grafts, the PRP loaded grafts (PRP-PLLA-HAp/M) induced significantly greater bone formation based on computed tomography, histological and immunohistochemical analyses. Our findings suggest that 3D PLLA nanofibrous matrices can be used as a graft material for irregular bone defects especially when combined with PRP as an osteogenic induction agent.