Shape-memory polymer actuators often contain crystallizable polyester segments. Here, the influence of accelerated hydrolytic degradation on the actuation performance in copolymer networks based on oligo(ε-caprolactone) dimethacrylate (OCL) and n-butyl acrylate is studied. The semi-crystalline OCL was utilized as crosslinker with molecular weights of 2.3 and 15.2 kg∙mol−1 (ratio: 1:1 wt%) and n-butyl acrylate (25 wt% relative to OCL content) acted as softening agent creating the polymer main chain segments within the network architecture. The copolymer networks were programmed by 50% elongation and were degraded by means of alkaline hydrolysis utilizing sodium hydroxide solution (pH = 13). Experiments were performed in the range of the broad melting range of the actuators at 40 °C. The degradation of test specimen was monitored by the sample mass, which was reduced by 25 wt% within 105 d. As degradation products, fragments of OCL with molecular masses ranging from 400 to 50.000 g·mol-1 could be detected by NMR spectroscopy and GPC measurements. The cleavage of ester groups included in OCL segments resulted in a decrease of the melting temperature (Tm) related to the actuator domains (amorphous at the temperature of degradation) and simultaneously, the Tm associated to the skeleton domain was increased (semi-crystalline at the temperature of degradation).

The alkaline hydrolysis decreased the polymer chain orientation of OCL domains until a random alignment of crystalline domains was obtained. This result was confirmed by cyclic thermomechanical actuation tests. The performance of directed movements decreased almost linearly as function of degradation time resulting in the loss of functionality when the orientation of polymer chains disappeared. Here, actuators were able to provide reversible movements until 91 d when the accelerated bulk degradation procedure using alkaline hydrolysis (pH = 13) was applied. Accordingly, a lifetime of more than one year can be guaranteed under physiological conditions (pH = 7.4) when, e.g., artificial muscles for biomimetic robots as potential application for these kind of shape-memory polymer actuators will be addressed.

Prostate cancer has a strong preference for metastasizing to bone which is the primary cause of prostate cancer-related morbidity and mortality. The complex nature of cancer metastasis requires the development of translational models that recapitulate a specific metastatic stage. Herein, we report the mimicking of mesenchymal to epithelial transition (MET) of prostate cancer cells using highly metastatic and a non-metastatic prostate cancer cell lines. A unique cell culture technique that we termed as ‘sequential culture’ was used to create a biomimetic bone microenvironment for metastasized prostate cancer cells by introducing bioactive factors from osteogenic induction of human mesenchymal stem cells (MSCs) within the porous 3D scaffolds. The in vitro 3D tumor model can be used as a testbed to study the interaction between prostate cancer and bone microenvironment and for the design of novel therapeutic studies.

Eggshell Membrane (ESM) is a naturally occurring proteinaceous microfibrous scaffold capable of mimicking the extracellular matrix (ECM). The extraction methodology deployed for its extraction process impedes its extensive application as a biomaterial in regenerative medicine. Herein, a unique route was deployed to decorate the surface of ESM with electrospun polycaprolactone (PCL) nanofiber in order to ameliorate the above problems and also fabricate a novel ECM mimicking bilayered scaffold for skin tissue engineering applications. Microstructural and surface topographic analysis confirms the formation of bilayered structure with smooth electrospun PCL nanofibers decorated on ESM. Carbodiimide chemistry was utilized to crosslink the two layers. Cytocompatibility evaluation of scaffolds was carried out with Human dermal fibroblast (HDF) cells. The biomimetic architecture and protein rich composition of as fabricated bilayered construct facilitated extensive cell adhesion, proliferation and migration in contrast the bare natural tissue led to impeded cell adhesion.

Periodontitis, or conventionally “Gum Disease,” is the infection and inflammation of gingival tissue, and is currently the leading cause of tooth loss in the United States. One of the most effective treatments of periodontitis is guided bone regeneration (GBR); however, current GBR barrier membranes lack high biocompatibility and cell impermeability. The authors of this study evaluated the in vitro viability of previously synthesized Gelatin-Pluronic® F127 hybrid hydrogels as potential GBR barrier membranes through a novel three-partition test involving migration of fluorescent-dyed human dermal fibroblasts. Results showed that cells were unable to migrate across the Gelatin-Pluronic® F127 hybrid hydrogel barrier, whereas control setups with gelatin hydrogel barriers showed cell permeability. In addition, cytotoxicity tests were conducted with fibroblasts plated in both cell mediums that had been incubated while in contact hybrid gels and cell mediums suspended on the surface of hybrid gels during swelling procedures. Fluorescence cell plate readings showed similar cell viability across data from both tests, indicating that Gelatin-Pluronic® F127 hybrid hydrogels are not toxic to cells, and thus biocompatible.

In this study, Zoledronic acid (ZOL), a type of nitrogen containing bisphosphonate, was loaded on graphene oxide (GO) particles to increase the particle size of the drug-nano-carrier complex which reduces drug filtration by the kidney and consequently, increases drug circulation time and its tumor uptake. The conjugation between ZOL and GO occurs via π− π stacking and hydrogen bonding interactions, and therefore, the drug may be gradually released from GO in physiological conditions which eliminates the need to apply high doses of the drug. Loading and release profile of ZOL on GO particles were investigated by using UV-Vis spectroscopy. Samples with different concentrations of 0.025-1.25 mg/ml of ZOL were loaded on 0.2 mg/ml GO. UV analysis showed that the maximum loading happens at ZOL to GO ratio of 1:0.2. This loading was obtained when 1 mg/ml of ZOL was initially loaded on 0.2 mg/ml of GO nanoparticles. The drug and drug carrier complexes were characterized by UV-vis spectroscopy.

Aerogels are light-weight porous materials that can tolerate the processing steps required for designing and creating an electric circuit such that the aerogel can be utilized as a substrate for device fabrication. Previous studies have shown the biostability and biocompatibility of polyurea crosslinked silica aerogels both in vivo and in vitro and have demonstrated the potential use of aerogels in biomedical applications. In vitro studies have shown that in the presence of an applied electric field neurites regeneration rate was greater on crosslinked silica aerogels than on tissue culture petridish used as a positive control. Currently, epineural suturing and nerve grafting are the gold standards for surgical reconstruction of injured nerves. However, because they rely on passive mechanisms for reapproximating the distal and proximal terminals they often lead to partial or no recovery leaving room for improvement. The present study investigates the feasibility of a wireless aerogel–based electrically-stimulating implant intended for nerve repair applications. Here the authors report on RF coupling between a secondary coil and a primary coil to wirelessly energize an interdigitated electrode array consisting of eleven interlocking fingers, created on a silica aerogel substrate. The coupling strength was tested both in air and in an animal model, as a function of distance and will be reported. This study focuses on in vivo evaluation and feasibility assessment of a novel active 3-D aerogel-based peripheral nerve repair device. The device utilizes induced EMF to establish a current (hence electrical stimulation) in predetermined pathways where nerve stumps will be confined to. Fundamental differences between in vitro and in vivo models necessitate the in vivo approach. The novel inductively-powered electrical stimulation aerogel-based device utilizes previously established 3-D confinement method for immobilization of nerve stumps, taking advantage of the mesoscopic surface roughness, unique to aerogels. The technique is tested on a mechanically strong, lightweight, porous, and biostable aerogel. Lithographic techniques, gold (Au) thin film metallization, and Faraday induction is used for circuit design, development, and activation.

Zoledronate (Zol) is a bone-preserving/ anti-tumoral drug that is widely used for the treatment of many cancers including spinal bone metastases. High systemic Zol doses required to elicit an adequate effect in the spine often lead to significant side effects, limiting its prolonged use and effectiveness. Here, we aim to provide an alternative strategy to locally deliver Zol at the tumor site. We show that nanoporous 3D-printed scaffolds can be loaded with Zol and possess the ability to release Zol (10-28%) over a sustained period. Additionally, we demonstrate that Zol-impregnated scaffolds, mostly Gel Lay, impair the proliferation of the prostate cancer cell line LAPC4 and the prostate-induced bone metastasis cells in vitro. 3D-printed nanoporous polymers offer a novel and versatile opportunity for potential local delivery of drugs in future clinical settings. These polymers can decrease systemic exposure and related side effects of Zol while at the same time concentrating the drug effect at the tumor site thereby inhibiting tumor proliferation. Also, these scaffolds could be co-printed or coupled with other materials to produce custom implants that offer better structural support for bone growth at the tumor site following resection.

Tricalcium phosphate (TCP) is a promising candidate in bone and dental tissue engineering applications. Though osteoconductive, its low osteoinductivity is a major concern. Trace elements addition at low concentrations are known for their impact on not only the osteoinductivity, but also physical and mechanical properties of TCP. Copper (Cu) is known for its role in vascularization and angiogenesis in biological systems. Here, we studied the effects of Cu addition on phase composition, porosity, microstructure and in vitro interaction with osteoblast (OB) cells. Our results showed that Cu stabilized the TCP structure, while no significant effect of microstructure and porosity was found. Cu at concentrations less than 1 wt.% did not have any cytotoxic effect while decreased proliferation of OBs were observed at 1 wt.% Cu doped TCP. Addition of Cu upregulated collagen type I and vascular endothelial growth factor expression in a dose dependent manner at early time-point. Furthermore, Cu reduced inflammatory gene expression by human osteoblasts. These findings show that addition of Cu to TCP may provide a therapeutic strategy that can be applied in bone tissue engineering applications.