Conceptually, the in vivo bioreactor was borne from complications in a repair method of bone fracture, bone loss, necrosis, and tumor reconstruction known as bone grafting. Traditional bone grafting strategies require fresh, autologous bone harvested from the iliac crest; this harvest site is limited by the amount of bone that can safely be removed, as well as associated pain and morbidity. Other methods include cadaverous allografts and synthetic options (often made of hydroxyapatite) that have become available in recent years. In response to the question of limited bone sourcing, it has been posited that bone can be grown to fit a damaged region within the body through the application of tissue engineering principles.
Tissue engineering is a biomedical engineering discipline that combines biology, chemistry, and engineering to design neotissue (newly formed tissue) on a scaffold. Tissues scaffolds are functionally identical to the extracellular matrix found, acting as a site upon which regenerative cellular components adsorb to encourage cellular growth. This cellular growth is then artificially stimulated by additive growth factors in the environment that encourage tissue formation. The scaffold is often seeded with stem cells and growth additives to encourage a smooth transition from cells to tissues, and more recently, organs. Traditionally, this method of tissue engineering is performed in vitro, where scaffold components and environmental manipulation recreate in vivo stimuli that direct growth. Environmental manipulation includes changes in physical stimulation, pH, potential gradients, cytokine gradients, and oxygen concentration. The overarching goal of in vitro tissue engineering is to create a functional tissue that is equivalent to native tissue in terms of composition, biomechanical properties, and physiological performance. However, in vitro tissue engineering suffers from a limited ability to mimic in vitro conditions, often leading to inadequate tissue substitutes. Therefore, in vivo tissue engineering has been suggested as a method to circumvent the tedium of environmental manipulation and use native in vivo stimuli to direct cell growth. To achieve in vivo tissue growth, an artificial bioreactor space must be established in which cells may grow. The in vivo bioreactor depends on harnessing the reparative qualities of the body to recruit stem cells into an implanted scaffold, and utilize vasculature to supply all necessary growth components.