Biophysical Stimulation for Bone Regeneration.

Tissue engineering involves the restoration of tissue structure or function through the use of cells, scaffolds, and regulators to stimulate growth [1]. The central paradigm in bone tissue engineering involves the use of a biomaterial scaffold, which can include osteoprogenitor cells and growth factors to stimulate bone growth. Tissue on this scaffold can be grown in vitro and then implanted (red route, Figure 1), or it can be directly implanted to facilitate bone regeneration in vivo (black route, Figure 1). A major goal in the design of this formulation is to promote healing by recreating the bone tissue microenvironment, which is responsible for regulating the osteoprogenitor cell function to maintain homeostasis [1]. Essential to this micronenvironment are stimulating factors that promote the osteoinductive capacity of the scaffold and which include biochemical, mechanical and electromagnetic stimuli. There have been significant efforts in the past decade to develop tissue engineering strategies based on this paradigm to regenerate bone tissue damaged as a result of injuries or conditions such as caneurysmal bone cysts, enchondroma and congenital pseudarthrosis [2]. This has required the formation of multi-disciplinary teams that apply principles of engineering and the life sciences to restore tissue structure and function. Although there have been progress in delivering these solutions to the clinic, the promises of tissue engineering 20 years ago have still to come. There is high urgency for tissue-engineered products which can achieve these expectations [3,4]. One of the essential components of the bone tissue microenvironment is biochemical and biophysical stimulation that promote the osteoinductive capacity of the scaffold. Most efforts have focused on the delivery of exogenous biochemical stimuli such as growth factors. Effective delivery of these biochemical stimuli has proven a challenge because of loss of bioactivity, limited control over dose administration, nontargeted delivery, and lack of availability of required growth factors [5]. An area in bone tissue engineering that has not been given the proper attention is the application of biophysical cues, such as the forces that result from weight-bearing exercise or the application of electromagnetic fields. This has prompted an opportunity in the search for mechanical and electromagnetic stimulatory alternatives for bone tissue regeneration.