Free thiol groups on poly(aspartamide) based hydrogels facilitate tooth-derived progenitor cell proliferation and differentiation

Cell-based tissue reconstruction is an important field of regenerative medicine. Stem and progenitor cells derived from tooth-associated tissues have strong regeneration potential. However, their in vivo application requires the development of novel scaffolds that will provide a suitable three-dimensional (3D) environment allowing not only the survival of the cells but eliciting their proliferation and differentiation. Our aim was to study the viability and differentiation capacity of periodontal ligament cells (PDLCs) cultured on recently developed biocompatible and biodegradable poly(aspartamide) (PASP)-based hydrogels. Viability and behavior of PDLCs were investigated on PASP-based hydrogels possessing different chemical, physical and mechanical properties. Based on our previous results, the effect of thiol group density in the polymer matrix on cell viability, morphology and differentiation ability is in the focus of our article. The chemical composition and 3D structures of the hydrogels were determined by FT Raman spectroscopy and Scanning Electron Microscopy. Morphology of the cells was examined by phase contrast microscopy. To visualize cell growth and migration patterns through the hydrogels, two-photon microscopy were utilized. Cell viability analysis was performed according to a standardized protocol using WST-1 reagent. PDLCs were able to attach and grow on PASP-based hydrogels. An increase in gel stiffness enhanced adhesion and proliferation of the cells. However, the highest population of viable cells was observed on the PASP gels containing free thiol groups. The presence of thiol groups does not only enhance viability but also facilitates the osteogenic direction of the differentiating cells. These cell-gel structures seem to be highly promising for cell-based tissue reconstruction purposes in the field of regenerative medicine

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

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

Fabrication of Mechanically Enhanced, Suturable, Fibrous Hydrogel Membranes

Poly(vinyl-alcohol) hydrogels have already been successfully utilised as drug carrier systems and tissue engineering scaffolds. However, lacking mechanical strength and suturability hinders any prospects for clinical and surgical applications. The objective of this work was to fabricate mechanically robust PVA membranes, which could also withstand surgical manipulation and suturing. Electrospun membranes and control hydrogels were produced with 61 kDa PVA. Using a high-speed rotating cylindrical collector, we achieved fibre alignment (fibre diameter: 300 ± 50 nm). Subsequently, we created multilayered samples with different orientations to achieve multidirectional reinforcement. Finally, utilising glutaraldehyde as a cross-linker, we created insoluble fibrous-hydrogel membranes. Mechanical studies were performed, confirming a fourfold increase in the specific loading capacities (from 0.21 to 0.84 Nm2/g) in the case of the monolayer samples. The multilayered membranes exhibited increased resistance from both horizontal and vertical directions, which varies according to the specific arrangement. Finally, the cross-linked fibrous hydrogel samples not only exhibited specific loading capacities significantly higher than their counterpart bulk hydrogels but successfully withstood suturing. Although cross-linking optimisation and animal experiments are required, these membranes have great prospects as alternatives to current surgical meshes, while the methodology could also be applied in other systems as well

Tissue-Engineered Poly(Vinyl Alcohol) Mesh Prospects in Abdominal Hernia Treatment

Introduction: As one of the most frequent disorders treated in general surgery, treatment of hernias has evolved throughout the years with the current first-choice treatment being hernioplasty via a laparoscopic or open-surgery approach. Currently applied non-biodegradable surgical meshes may cause complications more often than expected. The aim of our research was the synthesis and production of a biocompatible, biodegradable surgical mesh that could serve as a potential candidate for abdominal hernia repair.Materials and Methods: Nanofabricated poly (vinyl alcohol) (PVA) scaffolds were produced via electrospinning from a mixture of PVA and glutaraldehyde (GDA) solutions. Post electrospinning processing included folding, compression and cross-linkage formation via scaffold immersion in HCl solution. Samples were sterilized with ClO2 then stored in PBS at 37 C. The mechanical properties were assessed by an Instron 5942, in different setups recreating surgical conditions. In vivo examination was performed on Wistar Rats (n=45), which were randomly sorted into three groups of 15 animals each. In Group I and II, an artificial abdominal defect (2 x 2 cm) was created then PVA meshes (D: 2.5 cm) were used to repair it. Group III was a control group where only an incision on the skin and muscle was made. Animals were terminated after the 7th, 14th, 28th, 90th and 180th postoperative days. Implants were evaluated macroscopically and microscopically.Results: All animals survived until termination date. Upon inspection, no signs of infection or other adverse reaction were found in the environment of the scaffolds. Adhesion formation was found along the suture line rather than the PVA scaffold itself proving its biocompatibility. Histological examination revealed that the meshes were integrated to the host tissue and kept their structure.Conclusion: Our positive results reinforced that a PVA nanofabricated mesh is biocompatible and could be a viable candidate in treatment of abdominal hernias in the future