© 2019 by the author. Licensee MDPI, Basel, Switzerland. Biomaterial enhanced regeneration (BER) falls mostly under the broad heading of Tissue Engineering: the use of materials (synthetic and natural) usually in conjunction with cells (both native and genetically modified as well as stem cells) and/or biological response modifiers (growth factors and cytokines as well as other stimuli, which alter cellular activity). Although the emphasis is on the biomaterial as a scaffold it is also the use of additive bioactivity to enhance the healing and regenerative properties of the scaffold. Enhancing regeneration is both moving more toward regeneration but also speeding up the process. The review covers principles of design for BER as well as strategies to select the best designs. This is first general design principles, followed by types of design options, and then specific strategies for applications in skin and load bearing applications. The last section, surveys current clinical practice (for skin and load bearing applications) including limitations of these approaches. This is followed by future directions with an attempt to prioritize strategies. Although the review is geared toward design optimization, prioritization also includes the commercializability of the devices. This means a device must meet both the clinical performance design constraints as well as the commercializability design constraints.