Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology.

One of the most common medical interventions to reopen an occluded vessel is the implantation of a coronary stent. While this method of treatment is effective initially, restenosis, or the re-narrowing of the artery frequently occurs largely due to neointimal hyperplasia of smooth muscle cells. Drug eluting stents were developed in order to provide local, site-specific, controlled release of drugs that can inhibit neointima formation. By implementing a controlled release delivery system it may be possible to control the time release of the pharmacological factors and thus be able to bypass some of the critical events associated with stent hyperplasia and prevent the need for subsequent intervention. However, since the advent of first-generation drug eluting stents, long-term adverse effects have raised concerns regarding their safety. These limitations in safety and efficacy have triggered considerable research in developing biodegradable stents and more potent drug delivery systems. In this review, we shed light on the current state-of-the-art in drug eluting stents, problems related to them and highlight some of the ongoing research in this area.

Treatment of cancer using nanoparticle-based approaches relies on the rational design of carriers with respect to size, charge, and surface properties. Polymer-based nanomaterials, inorganic materials such as gold, iron oxide, and silica as well as carbon based materials such as carbon nanotubes and graphene are being explored extensively for cancer therapy. The challenges associated with the delivery of these nanoparticles depend greatly on the type of cancer and stage of development. This review highlights design considerations to develop nanoparticle-based approaches for overcoming physiological hurdles in cancer treatment, as well as emerging research in engineering advanced delivery systems for the treatment of primary, metastatic, and multidrug resistant cancers. A growing understanding of cancer biology will continue to foster development of intelligent nanoparticle-based therapeutics that take into account diverse physiological contexts of changing disease states to improve treatment outcomes.

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About 70% of pharmaceutical drug candidates are poorly soluble and suffer from low oral bioavailability. Additionally, a large number of therapeutics are also substrates for P-glycoprotein (P-gp) receptors present on the intestinal cell lining and undergo efflux that further reduces their oral bioavailability drastically. Nanoscale hydrogels are promising candidates for oral delivery of hydrophobic therapeutics as they hold immense potential in improving solubility and increasing intestinal permeability of such therapeutics. In this report, we describe the in vitro evaluation and comparison of four novel, pH-responsive poly(methacrylic acid-g-polyethylene glycol-co-hydrophobic monomer) nanoscale hydrogels for their capacity to load and release chemotherapeutic doxorubicin, as well as their ability to modulate permeability in vitro for improving doxorubicin transport. The resulting nanoscale formulations showed appreciable loading, and in vitro release studies demonstrated excellent pH-triggered release kinetics. These nanoscale hydrogels can serve as carriers for oral delivery of doxorubicin, achieving drug loading efficiencies of 56−70%, and releasing up to 95% of drug within 6 h. Powder X-ray diffraction studies revealed a change from the crystalline nature of doxorubicin to an amorphous form when encapsulated within formulations, illustrating their potential of enhancing solubility and stability for oral delivery of the hydrophobic therapeutic. Furthermore, their ability to modulate in vitro intestinal permeability was also studied using transport studies with Caco-2 cells, and was complemented by assessing their antitumor activity against P-gp overexpressing, DOXresistant H69/LX4 cancer cells. In vitro cell culture tests demonstrated up to 50% reduction in cellular proliferation in the case of poly(methacrylic acid-g-polyethylene glycol-co-methyl methacrylate), suggesting that these carriers are most suitable as hydrophobic drug carriers that can potentially overcome solubility and permeability limitations typically faced by hydrophobic therapeutics in the gastrointestinal (GI) tract.

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