In Vitro Effects of Waterborne Polyurethane 3D Scaffolds Containing Poly(lactic-co-glycolic acid)s of Different Lactic Acid/Glycolic Acid Ratios on the Inflammatory Response.

The physical and chemical properties of tissue engineering scaffolds have considerable effects on the inflammatory response at the implant site in soft tissue repair. The development of inflammation-modulating polymer scaffolds for soft tissue repair is attracting increasing attention. In this study, in order to regulate the inflammatory response at the implant site, a series of waterborne polyurethane (WPU) scaffolds with different properties were synthesized using polyethylene glycol (PEG), polycaprolactone (PCL) and poly (lactic acid)-glycolic acid copolymers (PLGAs) with three lactic acid/glycolic acid (LA/GA) ratios as the soft segments. Then, scaffolds were obtained using freeze-drying. The WPU scaffolds exhibited a porous cellular structure, high porosity, proper mechanical properties for repairing nerve tissue and an adjustable degradation rate. In vitro cellular experiments showed that the degradation solution possessed high biocompatibility. The in vitro inflammatory response of C57BL/6 mouse brain microglia (immortalized) (BV2) cells demonstrated that the LA/GA ratio of the PLGA in WPU scaffolds can regulate the external inflammatory response by altering the secretion of IL-10 and TNF-α. Even the IL-10/TNF-α of PU5050 (3.64) reached 69 times that of the control group (0.053). The results of the PC12 culture on the scaffolds showed that the scaffolds had positive effects on the growth, proliferation and differentiation of nerve cells and could even promote the formation of synapses. Overall, these scaffolds, particularly the PU5050, indeed prevent BV2 cells from differentiating into a pro-inflammatory M1 phenotype, which makes them promising candidates for reducing the inflammatory response and repairing nerve tissue. Furthermore, PU5050 had the best effect on preventing the transformation of BV2 cells into the pro-inflammatory M1 phenotype.

Tough and biodegradable polyurethane-curcumin composited hydrogel with antioxidant, antibacterial and antitumor properties.

The functionalization of tough and biodegradable hydrogels is an important way to broaden their applications in biomedical field. However, most of the hydrophobic functional drugs are difficult to incorporate with the hydrogels. In this work, curcumin (Cur), a hydrophobic functional drug, was chosen to composite with polyurethane (PU) to obtain PU-Cur hydrogels by a direct and simple in-situ copolymerization. The incorporation of curcumin in PU hydrogel increases the crosslink but reduces the hydrophilicity and degradation rate of PU-Cur hydrogels. Thus, it can increase the mechanical strength to a maximum of 6.4±0.8 MPa and initial modulus to a maximum of 3.0±0.4 MPa. More importantly, curcumin incorporated in PU networks is not deactivated. The degradation products of PU-Curs at relatively low concentrations (2.5 mg/mL) can scavenge free radicals very efficiently (maximum over 90%), which exhibits strong antioxidant properties to improve wound healing. Moreover, based on the photochemical activity of curcumin, notable inhibition effects of the degradation products of PU-Curs against bacteria (maximum over 80%) and cancer cells are demonstrated with blue light treatment as a photodynamic therapy (PDT). Therefore, the beneficial effects of curcumin are retained in PU-Cur hydrogels, suggesting potential use as wound dressings or tumor isolation membranes. This work proposes a promising strategy to combine hydrophobic functional drugs with hydrophilic hydrogels for applications in a wide range of biomaterials.

Bioactive 3D porous cobalt-doped alginate/waterborne polyurethane scaffolds with a coral reef-like rough surface for nerve tissue engineering application.

Nerve injuries in the central or peripheral nervous system threaten human health and hinder social development, and effectively repairing or regenerating nerve tissues remains a huge challenge. The rise of tissue engineering strategies has brought new light for this. Similar to the extracellular matrix, biomimetic three-dimensional (3D) porous scaffolds can provide biophysical and biochemical cues to guide cell behaviors and support tissue growth. Here, we prepared a hybrid cobalt-doped alginate/waterborne polyurethane 3D porous scaffold with nano-topology of a "coral reef-like" rough surface via two-step freeze-drying. The experimental results demonstrated that the "coral reef-like" rugged surface topology and bioactive cobalt dopant synergistically promote the neurite outgrowth and up-regulate the synaptophysin expression of neuron-like cells PC12 on the scaffold. Furthermore, the scaffold notably relieved the inflammatory response of microglial cells BV2 with the transformation from pro-inflammatory (M1) to anti-inflammatory (M2) phenotype. We believe that this 3D porous scaffold offers bright design inspiration for neural tissue engineering scaffolds and holds potential applications in nerve repair.

Dual-encapsulated biodegradable 3D scaffold from liposome and waterborne polyurethane for local drug control release in breast cancer therapy.

Compared with the traditional chemotherapy by injection, local release of drugs in the lesion area is a more efficient and less harmful treatment for solid tumors. However, the selection of appropriate drug carrier and controlled release of chemotherapy drugs are still great challenges. Herein, a kind of dual-encapsulated three-dimensional (3D) scaffold is designed for local drug release via blending the paclitaxel (PTX) loaded phospholipid liposomes with waterborne polyurethane (PU) by freeze-drying. The controlled release of paclitaxel is carried out through two simultaneous procedures. First, liposomes encapsulated in polyurethane scaffold can slowly release by water absorption and degradation of polyurethane. Then paclitaxel encapsulated in liposomes can also be released into water. Compared with the polyurethane scaffold which directly encapsulated paclitaxel, dual-encapsulated scaffold has slower initial release amount and maintain higher concentration of paclitaxel in later stage. Moreover, the protection of the phospholipid layer can prevent paclitaxel from being quickly decomposed and cleared, which could greatly improve the bioavailability and therapeutic effect of paclitaxel. Cell experiment results can be seen that dual-encapsulated scaffold not only has higher inhibition rate to the breast cancer MCF7 cells, but also has less damage to normal tissue cells. It provides a more effective platform for the local drug therapy in the treatment of tumors.[Formula: see text].

A waterborne polyurethane 3D scaffold containing PLGA with a controllable degradation rate and an anti-inflammatory effect for potential applications in neural tissue repair.

Currently, implanting tissue engineering scaffolds is one of the treatment methods for the regeneration of damaged tissues. The matching of the degradation rate of the scaffolds with the regeneration rate of the damaged zone is a big challenge in tissue engineering. Here, we have synthesized a series of biodegradable waterborne polyurethane emulsions and fabricated three-dimensional (3D) connected porous polyurethane scaffolds by freeze-drying. The degradation rate of the scaffolds was controlled by adjusting the relative ratio of poly-ε-caprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) in the soft segment. The degradation rate of the scaffolds gradually accelerated with the increase of the relative proportion of PLGA. By co-culture with BV2 microglia, the scaffolds promoted the differentiation of BV2 into an anti-inflammatory M2 phenotype rather than a pro-inflammatory M1 phenotype as the proportion of PLGA increases. When the BV2 cells were stimulated with lipopolysaccharide (LPS), the scaffolds with a higher PLGA ratio showed a much stronger anti-inflammatory effect. Then, we demonstrated that the scaffolds could promote the PC12 neurons to differentiate into neurites. Therefore, we believe that the polyurethane scaffolds have a promising potential application in neural tissue repair.