Biomimetic Electrospun Coatings Increase the In Vivo Sensitivity of Implantable Glucose Biosensors

In vivo tissue responses and functional efficacy of electrospun membranes based on polyurethane (PU) and gelatin (GE) as biomimetic coatings for implantable glucose biosensors was investigated in a rat subcutaneous implantation model. Three electrospun membranes with optimized fibre diameters, pore sizes and permeability, both single PU and co-axial PU-GE fibres and a solvent cast PU film were implanted in rats to evaluate tissue responses. For functional efficacy testing, four sensor variants coated with the above mentioned electrospun membranes as mass-transport limiting and outermost biomimetic coatings were implanted in rats. The electrospun PU membranes had micron sized pores that were not permeable to host cells when implanted in the body. However, PU-GE coaxial fibre membranes, having similar sized pores, were infiltrated with fibroblasts that deposited collagen in the membrane’s pores. Such tissue response prevented the formation of dense fibrous capsule around the sensor coated with the PU-GE co-axial fibre membranes, which helped improve the in vivo sensitivity for at least 3 weeks compared to the traditional sensors in rat subcutaneous tissue. Furthermore, the better in vitro sensor’s sensitivity due to electrospun PU as the mass-transport limiting membrane translated to better in vivo sensitivity. Thus, this study showed that electrospun membranes can play an important role in realising long in vivo sensing lifetime of implantable glucose biosensors.This work was financially supported by the Royal Society, UK (Research Grant, Ref. No.: RG100129), and the National Institute of Health, USA (NIH/NIBIB, grant R01EB001640). Ning Wang acknowledges the studentship for her Ph.D. from Brunel Institute for Bioengineering, Brunel University. The authors also acknowledge the support and the guidance from Prof. Francis Moussy for this study

Living Bacterial Sacrificial Porogens to Engineer Decellularized Porous Scaffolds

Decellularization and cellularization of organs have emerged as disruptive methods in tissue engineering and regenerative medicine. Porous hydrogel scaffolds have widespread applications in tissue engineering, regenerative medicine and drug discovery as viable tissue mimics. However, the existing hydrogel fabrication techniques suffer from limited control over pore interconnectivity, density and size, which leads to inefficient nutrient and oxygen transport to cells embedded in the scaffolds. Here, we demonstrated an innovative approach to develop a new platform for tissue engineered constructs using live bacteria as sacrificial porogens. E.coli were patterned and cultured in an interconnected three-dimensional (3D) hydrogel network. The growing bacteria created interconnected micropores and microchannels. Then, the scafold was decellularized, and bacteria were eliminated from the scaffold through lysing and washing steps. This 3D porous network method combined with bioprinting has the potential to be broadly applicable and compatible with tissue specific applications allowing seeding of stem cells and other cell types

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051