Disclosed herein are biointerface membranes including a macro-architecture and a micro-architecture co-continuous with and bonded to and/or located within at least a portion of the macro-architecture. The macro- and micro-architectures work together to manage and manipulate the high-level tissue organization and the low-level cellular organization of the foreign body response in vivo, thereby increasing neovascularization close to a device-tissue interface, interfering with barrier cell layer formation, and providing good tissue anchoring, while reducing the effects of motion artifact, and disrupting the organization and/or contracture of the FBC. The biointerface membranes of the preferred embodiments can be utilized with implantable devices such as devices for the detection of analyte concentrations in a biological sample (for example, from a body), cell transplantation devices, drug delivery devices, electrical signal delivering or measuring devices, and/or combinations thereof.