Natural rubber - Increasing diversity of an irreplaceable renewable resource.

This paper discusses the importance of introducing domestic natural rubber production and presents the rediscovery of a rubber-producing species, Scorzonera tau-saghyz or "mountain gum", originally discovered in 1929 on the Karatau mountains in Kazakhstan. This plant could potentially also be cultivated in the U.S. In this exploratory work, roots (2-5 years old) were harvested on June 16, 2021 from wild strands in the Karatau mountains, Kumantas ridge, and Saraba, Kazakhstan, and processed at the Ohio State University. The rubber extraction method was based on an indigenous method in Kazakhstan to make natural chewing gum. Water extraction followed by purification yielded 16.2 wt% rubber from the dry roots, in comparison with 4-8 wt% from most rubber dandelion (Taraxacum kok-saghyz) plants, also a potential domestic rubber producing plant. High-resolution size exclusion chromatography was used to analyze rubber samples. The molecular weights and gel and oligomer contents were very similar to the rubber from Hevea brasiliensis, the current commercial source of natural rubber. More detailed investigations of this very interesting rubber-producing plant are in progress.

Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak.

This paper describes the synthesis and characterization of new bivalent folate-targeted PEGylated doxorubicin (FA2-dPEG-DOX2) made by modular chemo-enzymatic processes using Candida antarctica lipase B (CALB) as a biocatalyst. Unique features are the use of monodisperse PEG (dPEG) and the synthesis of thiol-functionalized folic acid yielding exclusive γ-conjugation of folic acid (FA) to dPEG. The polymer-based drug conjugate is built up by a series of transesterification and Michael addition reactions all catalyzed be CALB. In comparison with other methods in the literature, the modular approach with enzyme catalysis leads to selectivity, full conversion and high yield, and no transition metal catalyst residues. The intermediate product with four acrylate groups is an excellent platform for Michael-addition-type reactions for a wide variety of biologically active molecules. The chemical structures were confirmed by nuclear magnetic resonance spectroscopy (NMR). Flow cytometry analysis showed that, at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 were taken up by 99.9% of triple-negative breast cancer cells in 2 h. Fluorescence was detected for 5 days after injecting compound IV into mice. Preliminary results showed that intra-tumoral injection seemed to delay tumor growth more than intravenous delivery.

An Implantable Magneto-Responsive Poly(aspartamide) Based Electrospun Scaffold for Hyperthermia Treatment.

When exposed to an alternating magnetic field, superparamagnetic nanoparticles can elicit the required hyperthermic effect while also being excellent magnetic resonance imaging (MRI) contrast agents. Their main drawback is that they diffuse out of the area of interest in one or two days, thus preventing a continuous application during the typical several-cycle multi-week treatment. To solve this issue, our aim was to synthesise an implantable, biodegradable membrane infused with magnetite that enabled long-term treatment while having adequate MRI contrast and hyperthermic capabilities. To immobilise the nanoparticles inside the scaffold, they were synthesised inside hydrogel fibres. First, polysuccinimide (PSI) fibres were produced by electrospinning and crosslinked, and then, magnetitc iron oxide nanoparticles (MIONs) were synthesised inside and in-between the fibres of the hydrogel membranes with the well-known co-precipitation method. The attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) investigation proved the success of the chemical synthesis and the presence of iron oxide, and the superconducting quantum interference device (SQUID) study revealed their superparamagnetic property. The magnetic hyperthermia efficiency of the samples was significant. The given alternating current (AC) magnetic field could induce a temperature rise of 5 °C (from 37 °C to 42 °C) in less than 2 min even for five quick heat-cool cycles or for five consecutive days without considerable heat generation loss in the samples. Short-term (1 day and 7 day) biocompatibility, biodegradability and MRI contrast capability were investigated in vivo on Wistar rats. The results showed excellent MRI contrast and minimal acute inflammation.

Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment.

This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA2-dPEG-DOX2). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation.

Early and late effects of absorbable poly(vinyl alcohol) hernia mesh to tissue reconstruction.

Hernia is a defect of the abdominal wall. Treatment is principally surgical mesh implantation. Non-degradable surgical meshes produce numerous complications and side-effects such as inflammatory response, mesh migration and chronic pain. In contrast, the biodegradable, poly (vinyl alcohol) (PVA) based polymers have excellent chemical, mechanical and biological properties and after their degradation no chronic pain can be expected. The toxicology of PVA solution and fibers was investigated with Human dermal fibroblast- Adult cell line. Implantation tests were observed on long-term contact (rat) and large animal (swine) models. To measure the adhesion formation, Diamond and Vandendael score were used. Macroscopical and histological responses were graded from the samples. In vitro examination showed that PVA solution and fibers are biocompatible for the cells. According to the implantation tests, all samples were integrated into the surrounding tissue, and there was no foreign body reaction. The average number of adhesions was found on the non-absorbable suture line. The biocompatibility of the PVA nanofiber mesh was demonstrated. It has a non-adhesive, non-toxic and good quality structure which has the potential to be an alternative solution for the part of the hernia mesh.

Polyisobutylene-New Opportunities for Medical Applications.

This paper presents the results of the first part of testing a novel electrospun fiber mat based on a unique macromolecule: polyisobutylene (PIB). A PIB-based compound containing zinc oxide (ZnO) was electrospun into self-supporting mats of 203.75 and 295.5 g/m2 that were investigated using a variety of techniques. The results show that the hydrophobic mats are not cytotoxic, resist fibroblast cell adhesion and biofilm formation and are comfortable and easy to breathe through for use as a mask. The mats show great promise for personal protective equipment and other applications.

Poly(amino acid) based fibrous membranes with tuneable in vivo biodegradation.

In this work two types of biodegradable polysuccinimide-based, electrospun fibrous membranes are presented. One contains disulfide bonds exhibiting a shorter (3 days) in vivo biodegradation time, while the other one has alkyl crosslinks and a longer biodegradation time (more than 7 days). According to the mechanical measurements, the tensile strength of the membranes is comparable to those of soft the connective tissues and visceral tissues. Furthermore, the suture retention test suggests, that the membranes would withstand surgical handling and in vivo fixation. The in vivo biocompatibility study demonstrates how membranes undergo in vivo hydrolysis and by the 3rd day they become poly(aspartic acid) fibrous membranes, which can be then enzymatically degraded. After one week, the disulfide crosslinked membranes almost completely degrade, while the alkyl-chain crosslinked ones mildly lose their integrity as the surrounding tissue invades them. Histopathology revealed mild acute inflammation, which diminished to a minimal level after seven days.

Investigation of the Cytotoxicity of Electrospun Polysuccinimide-Based Fiber Mats.

This study investigated cell viability in the presence of allylamine-modified and plasma-treated electrospun polysuccinimide fiber mats (PSI-AAmp). Low pressure non-equilibrium plasma was used for crosslinking the PSI-AAm. Comparison of FTIR and XPS analyses demonstrated that crosslinking occurred on the surface of the samples. Cell viability was investigated using the MG-63 osteosarcoma cell line and WST-1 viability reagent. Since PSI hydrolyzes to poly(aspartic acid) (PASP), PASP was used in addition to the regular controls (cells only). Phase contrast showed normal morphology in all cases at 24 h; however, in the presence of PSI-AAmp at 72 h, some rounded, dead cells could also be seen, and proliferation was inhibited. Since proliferation in the presence of PASP alone was not inhibited, the cause of inhibition was not the final product of the hydrolysis. Further investigations will be carried out to pinpoint the cause.

Poly(amino acid)-Based Gel Fibers with pH Responsivity by Coaxial Reactive Electrospinning.

Electrospinning is a well-known technique for the preparation of scaffolds for biomedical applications. In this work, a continuous electrospinning method for gel fiber preparation is presented without a spinning window. As proof of concept, the preparation of poly(aspartic acid)-based hydrogel fibers and their properties are described by using poly(succinimide) as shell polymer and 2,2,4(2,4,4)-trimethyl-1,6-hexanediamine as cross-linker in the core of the nozzle. Cross-linking takes place as the two solutions get in contact at the tip of the nozzle. The impact of solution concentrations and feeding rates on fiber morphology, proof of the presence of cross-links as well as pH sensitivity after the transformation of the poly(succinimide)-based material to poly(aspartic acid) is presented.

Kinetics of volume change of poly(succinimide) gels during hydrolysis and swelling.

Kinetics of hydrolysis induced swelling as well as pure swelling of a novel class of pH responsive biocompatible polymer gels was studied. Poly(aspartic acid) gels were prepared by hydrolysis of chemically cross-linked poly(succinimide) networks. The volume change of spherical gels of different size, measured at constant pH, proceeds in three distinct processes: solvent exchange, hydrolysis and swelling. It turned out that pure swelling as well as the swelling coupled with hydrolysis can be described by the Tanaka-Fillmore-Peters-Candau theory. The relaxation times as well as the cooperative diffusion coefficient of the network chains were determined. It was found that the initial condition of the swelling makes its influence felt neither on the relaxation time, nor on the cooperative diffusion coefficient.