A new research and development for bone growth factor therapy, this involves the discovery of bone morphogenetic proteins (BMPs). Some organs, like the brain and spinal cord, are protected inside bone structures—the skull and vertebrae, respectively. Other organs, such as the muscles, are attached to the skeleton. The discovery of mesenchymal stem cells (MSCs) in 1991, coincident with the first isolation of human embryonic stem cells, also stimulated significant interest.

The skeleton is an adaptive structure, and as it grows through childhood, and the rest of the body grows along with it. Apart from providing structure and protection, the skeletal system functions to cooperate with joints and muscles for movement. Other critical functions of the skeletal system include blood cell production, mineral storage, and endocrine regulation

Finally, the development of materials mimicking bone extracellular matrix, including calcium phosphate ceramics, collagens, and glycosaminoglycans, exponentially increased the number of available alternatives to bone graft . With this, the concept of a tissue engineering “triangle” consisting of growth factors, cells, and scaffolds has continued to provide a growing list of bone graft substitutes.

The treatment of bone injury has been attempted as early as the beginning of medicine. Although not scientifically recorded, surgical interventions existed even in prehistoric times, as suggested by paleopathological evidence, such as set fractures, rickets, and drilled skulls. Materials such as animal bone, ivory, silver, and gold have been used to replace missing teeth or bones.

Later, as the result of the 19–20th-century technological revolution, the emergence of tools, such as high-resolution microscopy, histological and staining techniques, X-ray, computed tomography, and genomic and proteomic techniques, have boosted our understanding of bone biology enormously. Very large collaborative international research projects, such as the human genome project, the human proteome project, and the human protein atlas, have been completed or are underway.

Rather counterintuitively, this increasing tide of information has not created a proportionally clearer understanding of the interactions between the key biological systems of the human body. Every new signaling pathway adds more complexity and, unlike electronics, no one-input-one-output mechanism exists in biology.

The mere number of possible therapeutic combinations exceeds the capacity of any high-throughput screening system. Fortunately, concomitant with the accumulation of “big data” is the rise of machine learning and other methods to replace or augment the human researcher.

The outcome of this study is  tissue engineering of bone, which is not as basic as combining a few cell types on some scaffolds with certain growth factors, followed by implantation in vivo hoping for complete restoration of the tissue. As it moves from the bench to the bedside, a much deeper and more comprehensive understanding of bone biology, and medicine, must  be practical to modify the most suitable bone regenerating therapy for an individual patient.