Bone regenerative medicine: classic options, novel strategies, and future directions

Abstract

This review analyzes the literature of bone grafts and introduces tissue engineering as a strategy in this field of orthopedic surgery. We evaluated articles concerning bone grafts; analyzed characteristics, advantages, and limitations of the grafts; and provided explanations about bone-tissue engineering technologies. Many bone grafting materials are available to enhance bone healing and regeneration, from bone autografts to graft substitutes; they can be used alone or in combination. Autografts are the gold standard for this purpose, since they provide osteogenic cells, osteoinductive growth factors, and an osteoconductive scaffold, all essential for new bone growth. Autografts carry the limitations of morbidity at the harvesting site and limited availability. Allografts and xenografts carry the risk of disease transmission and rejection. Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects. The combined use of scaffolds, healing promoting factors, together with gene therapy, and, more recently, three-dimensional printing of tissue-engineered constructs may open new insights in the near future.

Figure 1

SEM ultramicrographs of microstructure of natural bone grafts. (A) Trabecular or cancellous bone graft. Note the porous honey comb-like microstructure of cancellous bone graft. (B) Cortico-cancellous bone graft. (C) Cortical or compact bone graft (scalebars (A-C) 100 μm).

Figure 2

Types of bone grafts. (A) Autograft: The surgeon harvests bone from another site of the patient's skeleton, often from the iliac crest, and implants it into the bone defect site. This type of bone grafts leads to two surgeries, thus, two scars, more pain, and additional infection risk. (B, C) Allograft and xenograft: Here the bone graft is obtained from a human donor or animal model, respectively. These types of bone grafts, particularly xenografts, carry the risk of immunologic response and transmission of viral and bacterial disease and with xenografts, zoonotic disease. (D) Synthetic bone graft substitute: There are different types of synthetic grafts. These biomaterials are safe and need no second surgery site.

Figure 3

SEM images. Alginate (A), alginate-chitosan (B), chitosan (C), chitosan-collagen (D), mesenchymal stem cells cultured on the scaffold collagen (C)-dl-lactic acid-glycolic acid (PLGA) (P) medium (E), and synthesized porous HA scaffold (F). The scaffolds used for bone tissue engineering must be porous (scalebars (A-D, F) 100 μm, (E) 500 μm).