Immobilization of FGF on Poly(xylitol dodecanedioic Acid) Polymer for Tissue Regeneration.

Fibroblast growth factor (FGF) plays a vital role in the repair and regeneration of most tissues. However, its low stability, short half-life, and rapid inactivation by enzymes in physiological conditions affect their clinical applications. Therefore, to increase the effectiveness of growth factors and to improve tissue regeneration, we developed an elastic polymeric material poly(xylitol dodecanedioic acid) (PXDDA) and loaded FGF on the PXDDA for sustained drug delivery. In this study, we used a simple dopamine coating method to load FGF on the surface of PXDDA polymeric films. The polydopamine-coated FGF-loaded PXDDA samples were then characterized using FTIR and XRD. The in vitro drug release profile of FGF from PXDDA film and cell growth behavior were measured. Results showed that the polydopamine layer coated on the surface of the PXDDA film enhanced the immobilization of FGF and controlled its sustained release. Human fibroblast cells attachment and proliferation on FGF-immobilized PXDDA films were much higher than the other groups without coatings or FGF loading. Based on our results, the surface modification procedure with immobilizing growth factors shows excellent application potential in tissue regeneration.

Polymer-Salt Aqueous Two-Phase System (ATPS) Micro-Droplets for Cell Encapsulation.

Biosample encapsulation is a critical step in a wide range of biomedical and bioengineering applications. Aqueous two-phase system (ATPS) droplets have been recently introduced and showed a great promise to the biological separation and encapsulation due to their excellent biocompatibility. This study shows for the first time the passive generation of salt-based ATPS microdroplets and their biocompatibility test. We used two ATPS including polymer/polymer (polyethylene glycol (PEG)/dextran (DEX)) and polymer/salt (PEG/Magnesium sulfate) for droplet generation in a flow-focusing geometry. Droplet morphologies and monodispersity in both systems are studied. The PEG/salt system showed an excellent capability of uniform droplet formation with a wide range of sizes (20-60 µm) which makes it a suitable candidate for encapsulation of biological samples. Therefore, we examined the potential application of the PEG/salt system for encapsulating human umbilical vein endothelial cells (HUVECs). A cell viability test was conducted on MgSO4 solutions at various concentrations and our results showed an adequate cell survival. The findings of this research suggest that the polymer/salt ATPS could be a biocompatible all-aqueous platform for cell encapsulation.

A Highly Elastic and Autofluorescent Poly(xylitol-dodecanedioic Acid) for Tissue Engineering.

In spite of the vast research on developing a highly elastic polymer for tissue regeneration, using a renewable resource and a simple, environment-friendly synthesis route to synthesize an elastic polymer has not been successfully achieved yet. The objective of this study was to use a simple melt condensation polymerization method to develop an elastic polymer for tissue regeneration applications. A nature-derived renewable, nontoxic, and inexpensive monomer, xylitol, and a cross-linking agent, dodecanedioic acid, were used to synthesize the new polymer named poly(xylitol-dodecanedioic acid) (PXDDA). Its physicochemical and biological properties were fully characterized. Fourier transform infrared (FTIR) results confirmed the formation of ester bonding in the polymer structure, and thermal analysis results demonstrated that the polymer was completely amorphous. The polymer is highly elastic. Increasing the molar ratio of dodecanedioic acid resulted in lower elasticity, higher hydrophobicity, and lower glass transition temperature. Further, the polymer degradation rate and in vitro dye release from the polymer also became slower when the amount of dodecanedioic acid in the composite increased. Biocompatibility studies showed that both the polymeric materials and the degraded products of the polymer did not show any toxicity. Instead, this new polymer significantly promoted cell adhesion and proliferation, compared to a widely used polymer, poly(lactic acid), and tissue culture plates. Interestingly, the PXDDA polymer demonstrated autofluorescent properties. Overall, these results suggest that a new, elastic, biodegradable polymer has been successfully synthesized, and it holds great promise for biomedical applications in drug delivery and tissue engineering.

3D-printed flexible polymer stents for potential applications in inoperable esophageal malignancies.

Palliation therapy for dysphagia using esophageal stents is the current treatment of choice for those patients with inoperable esophageal malignancies. However, the metallic and plastic stents currently used in the clinical setting may cause complications, such as tumor ingrowth and stent migration into the stomach. To effectively reduce/overcome these complications, we designed a tubular, flexible polymer stent with spirals. The parameters of the spirals were computationally optimized by using a finite element analysis. The designed polymer stents with optimized spirals were then printed by a 3D printing technique. 3D-printed tubular polymer stents without spirals served as controls. The self-expansion and anti-migration properties of the printed stent were characterized in an ex vivo normal porcine esophagus. The biodegradability test of the stent was performed in a neutral buffer and acidic gastric buffer. The cytotoxicity of the new stent was examined through the viability test of human esophagus epithelial cells. Results showed the self-expansion force of the 3D-printed polymer stent with spirals was higher than the stent without spirals. The anti-migration force of the 3D-printed stent with spirals was significantly higher than that of the stent without spirals. Furthermore, the stent with spirals significantly decreased the migration distance compared to the non-spiral 3D-printed polymer stent. Degradation study showed that the polymer materials started to degrade after six weeks and the compressive strength of the stent was not significantly decreased with time. In vitro cell viability results further indicated that the polymer stent does not have any cytotoxicity. Together, these results showed that the 3D-printed stent with spirals has potential applications in the treatment of inoperable esophageal malignancies. STATEMENT OF SIGNIFICANCE: In this study, we developed a new 3D-printed flexible tubular polymeric stent with spirals. The mechanical properties of the 3D-printed polymer stent are modulated by changing the ratios of PLA to TPU. The stent is flexible enough to be compressed in a clinically available stent delivery system, and can self-expand after it is released. The self-expansion force of the stent with spirals is higher than that of non-spiral stents. The spirals on the outside of the stent significantly increased the anti-migration force compared to non-spiral stents in an ex vivo normal pig esophagus. Together, the 3D-printed stent with spirals will bring promising potential in the treatment of inoperable esophagus malignancies or benign strictures.

Synthesis and Characterization of Biodegradable Semi-Interpenetrating Polymer Networks Based on Star-Shaped Copolymers of ɛ-Caprolactone and Lactide.

In this paper, the focus is on a new kind of biodegradable semi-interpenetrating polymer networks, which is derived from ɛ-caprolactone, lactide, 1,4-butane diisocyanate and ethylenediamine and also its potential has been investigated in soft tissue engineering applications. The polymers were characterized by nuclear magnetic resonance (NMR) spectrometry, Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). These experiments show that the polymers with the right composition and the expected molecular weight were achieved. Also, the in-vitro degradation of polymer network was examined in phosphate buffer solutions (pH 7.4) at 37 °C. Moreover, cell viability and adhesion tests were carried out with fibroblast cells by the MTT assay, which confirmed biocompatibility. Polyurethane materials have superior mechanical properties, so these biodegradable and biocompatible films demonstrate potential for future application as cell scaffolds in soft tissue engineering applications.

The application of cell sheet engineering in the vascularization of tissue regeneration.

Scaffold-free cell sheet engineering (CSE) is a new technology to regenerate injured or damaged tissues, which has shown promising potential in tissue regeneration. CSE uses a thermosensitive surface to form a dense cell sheet that can be detached when temperature decreases. The detached cell sheet can be stacked on top of one another according to the thickness of cell sheet for the specific tissue regeneration application. One of the key challenges of tissue engineering is vascularization. CSE technique provides excellent microenvironment for vascularization since the technique can maintain the intact cell matrix that is crucial for angiogenesis. In this review paper, we will highlight the principle technique of CSE and its application in tissue regeneration.