Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications

• Regenerative engineering has been recently proposed to regenerate skeletal tissue.
• Regenerative small molecules play a vital role in bone regenerative engineering.
• Numerous small molecules have been recently discovered for bone regeneration.
• Polymeric scaffolds play an important role to delivery small molecules in vivo.

Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potential clinical applications. New strategies for bone regeneration that involve inexpensive and stable small molecules can obviate these problems and have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration.