Enhanced wound healing using a 3D printed VEGF-mimicking peptide incorporated hydrogel patch in a pig model.

There is a need for effective wound healing through rapid wound closure, reduction of scar formation, and acceleration of angiogenesis. Hydrogel is widely used in tissue engineering, but it is not an ideal solution because of its low vascularization capability and poor mechanical properties. In this study, gelatin methacrylate (GelMA) was tested as a viable option with tunable physical properties. GelMA hydrogel incorporating a vascular endothelial growth factor (VEGF) mimicking peptide was successfully printed using a three-dimensional (3D) bio-printer owing to the shear-thinning properties of hydrogel inks. The 3D structure of the hydrogel patch had high porosity and water absorption properties. Furthermore, the bioactive characterization was confirmed by cell culture with mouse fibroblasts cell lines (NIH 3T3) and human umbilical vein endothelial cells. VEGF peptide, which is slowly released from hydrogel patches, can promote cell viability, proliferation, and tubular structure formation. In addition, a pig skin wound model was used to evaluate the wound-healing efficacy of GelMA-VEGF hydrogel patches; the results suggest that the GelMA-VEGF hydrogel patch can be used for wound dressing.

DNA bound to polypyrrole films: high-resolution imaging, DNA binding kinetics and internal migration.

We have studied the time-dependent uptake of 35S radiolabeled DNA with electrochemically prepared polypyrrole films. The two distinct polypyrrole film surfaces, a rough (solution polymeric growth face, R) and a smooth surface (electrode face, S) were characterized by low-resolution AFM and high-resolution transmission electron microscopy (TEM). These studies showed the presence of steep contours and defects in the form of large and small surface holes and valleys on the rough surface of polypyrrole. The void dimensions ranged from the nanoscale to micron size. By contrast, the smooth surface was flatter and largely devoid of significant structural defects and exhibited closer packing of the polypyrrole chains over large areas. Both surfaces were comprised largely of chains whose average diameters were 1.0-1.2 +/- 0.3 nm. The surface characterization studies were complemented by time-dependent DNA uptake studies which showed a t1/2-dependent total uptake of 35S DNA at higher levels on the rough surface compared to the smooth surface. This is consistent with the apparent higher effective surface area of the rough surface compared to the smooth. Using a proportional counter the time-dependent ratio (R/S) of the 35S DNA detected from the rough surface of the polypyrrole disk to that detected from the smooth surface suggested that DNA was migrating into the disk interior from its uptake surface. The rough side defect dimensions measured by TEM were more than sufficient to allow for the penetration and migration of DNA into the disk interior. Both R/S ratios were extrapolated and found to intersect at an R/S value close to 1.0, suggesting a kinetic process leading ultimately towards a nearly uniform radiolabeled DNA distribution in the disk. These kinetic results were in agreement with the surface characterization studies and suggest a model in which sizeable internal pores exist throughout the electrochemically prepared polypyrrole, that could account for the DNA migration effect. This was confirmed by TEM of the interior of a polypyrrole disk produced by Argon ion milling.

Prolonged regional nerve blockade. Injectable biodegradable bupivacaine/polyester microspheres.

BACKGROUND: Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has characterized implantable preparations of local anesthetics in polymer pellets for prolonged regional anesthesia. In this article, the authors characterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats. METHODS: Microspheres were prepared using polylactic-co-glycolic acid polymers loaded with 75% w/w bupivacaine by a solvent evaporation method. Bupivacaine release from microspheres was determined in vitro by ultraviolet spectroscopy and scintillation counting. Sensory and motor blockade of the rat sciatic nerve were assessed in vivo after injection of microsphere suspensions. RESULTS: Depending on the type of microspheres, the dose, and the additive used, mean duration of sciatic nerve block ranged from 10 h to 5.5 days. Incorporation of 0.05% w/w dexamethasone into the microspheres resulted in significant prolongation of block (up to 13-fold), and only preparations that contained dexamethasone produced blocks lasting beyond 1 day. Bupivacaine was released in a controlled manner in vitro. Dexamethasone does not substantially slow bupivacaine release from microspheres in vitro. CONCLUSIONS: Prolonged percutaneous blockade of peripheral nerves is feasible. The recovery from blockade is complete, and plasma bupivacaine levels are far below the range associated with systemic toxicity. The mechanisms underlying the dexamethasone block-prolonging effect are under investigation.

A study on the role of N-methyl-D-aspartate receptors in the rat visual cortex.

The amino acid L-glutamate is a major excitatory neurotransmitter in the central nervous system of vertebrates. NMDA (N-methyl-d-aspartate) is one of the L-glutamate receptor subtypes. During a critical period of early postnatal development, the visual cortex is susceptible to experience-dependent modification of neuronal responses. Recently, the activation of NMDA receptors has been supposed as a prerequisite for the induction of such modification. We therefore investigated developmental changes of NMDA receptors in the rat visual cortex and questioned whether they could be related to the visual development. We assessed the density of [3H]-NMDA receptor in the visual cortex of normally reared rate (Group I) and visually deprived rats (Group II) using quantitative autoradiography. The density of [3H]-NMDA receptor was significantly lower in Group II than in group I during the early postnatal period, and increased rapidly by postnatal 1 week and, decreased after postnatal 5 weeks. These results suggested that NMDA receptors may play a role in neuronal development in the visual cortex during the early postnatal period.

Experimental intraocular fibrovascular proliferation through sclerotomy wound.

In the process of closing scleral wounds caused by various conditions, incarceration of conjunctiva, Tenon's capsule, or vitreous in the wound can occur unexpectedly. We created such conditions experimentally in order to discover their intraocular complications. The experimental materials consisted of 12 albino rabbits (24 eyes) divided into two groups (Groups I & II). Vitrectomy was performed in the Group I rabbits (12 eyes) but not in the Group II rabbits (12 eyes). Flaps of conjunctiva and Tenon's capsule were made and inserted into the vitreous cavity through the sclerotomy site, which was soon closed. Fundal examination of the rabbits was carried out using an indirect ophthalmoscope at intervals after the procedure; first at 3 days, then at 1, 3, and 6 weeks, and then at 3 months and 6 months, respectively. Enucleation of the rabbits' eyes 4 from two different rabbits at each of these intervals was carried out, and the extracted eyes were examined under a light microscope at each interval. The results are summarized as follows: 1. All rabbit eyes studied showed intraocular fibrovascular proliferation. 2. The extent of tissue proliferation, which was proportional to the amount of vitreous hemorrhage, was greater in Group II than in Group I. 3. The proliferated tissue developed to "band" by three weeks postexperiment, after which it gradually regressed. 4. The fibrovascular band was made of fibroblasts, stromal matrix, and capillaries.