Development of Composite Scaffolds for Load-Bearing Segmental Bone Defects

Table 1

Stages of the bone-healing cascade. Adapted into a table form from [69].

Early inflammatory stage	Hematoma development: after injury blood permeates into the wound site, and a hematoma forms within hours.
	Granulation tissue formation: inflammatory cells including macrophages, monocytes, lymphocytes, and polymorphonuclear cells infiltrate the wound through blood. Fibroblasts also infiltrate the bone through the mediation of prostaglandin. This mixture results in the formation of granulation tissue.
	Ingrowth of vascular tissue: inflammatory cells forming the granulation tissue will also stimulate vasculogenesis.
	Migration of mesenchymal cells: this is the third and final process that is stimulated by the inflammatory cells found in the wound.
Repair stage	Stroma formation to support vasculature: during the first stage of the repair process, fibroblasts deposit stroma. This is aimed at supporting vasculature ingrowth.
	Vascular ingrowth progress: after the stroma is formed, vascular tissue can continue to grow and distribute nutrients to all areas of the wound.
	Mineralization of the osteoid: the collagen matrix is deposited by osteoblasts and subsequently is mineralized.
	Soft callus formation: mineralization of the osteoid leads to the formation of a soft callus around the wound area. The soft callus is a very weak structure that hardens as the callus ossifies. Any movement between bones during this stage will result in macrotrauma potentially disrupting the healing cascade.
	Woven bone formation: as the callus ossifies, the opposite bone extremities are bridged by woven bone formation.
Remodeling stage	Bone returns to original structure: the last stage of bone healing is also the longest, as it takes a minimum of 3 months and continues for the life of the bone. A factor that affects bone-remodeling time is adequate mechanical loading. This allows for the organic matrix to mineralize where needed and for bone to be resorbed where it is not.