Cells involved in callus formation differentiate from primitive mesenchymal cells, which originate from the bone marrow, periosteum, endothelial cells, and perivascular cells. The earliest differentiated cells are fibroblasts, which invade the organized hematoma along proliferating vascular buds, secreting type III collagen that constitutes the fibrous component of the callus. Subsequently, through differentiation of primitive mesenchymal cells into chondrocytes and chondrocyte proliferation, the content of type II collagen and proteoglycans rapidly increases, and cartilage islands begin to form in the fibrous matrix. The stability of the fracture site may determine the amount of cartilaginous callus formed. In the healing process of non-immobilized and non-rigidly fixed fractures, there is a greater cartilaginous component, while in the healing process of absolute fixation fractures, almost no cartilaginous component is observed.
The formation of bony callus occurs through two pathways: in the early stages of the repair phase, new trabecular bone forms near the old bone; this in situ bone formation does not require a cartilaginous stage. Cells involved in in situ bone formation originate from the periosteum, endosteum, and other sites. Ultimately, this in situ growth of trabecular bone and cartilage callus bridges the fracture ends. Later in the repair phase, the cartilage callus is gradually replaced by bony elements. This is achieved through the invasion of vascular sprouts, the degradation of the cartilage matrix by osteoclasts (or chondroclasts), the entry of osteoblasts, and the secretion of bone matrix proteins such as type I collagen. Finally, mineralization forms woven bone, resulting in a complete bony connection between the fracture ends.
The remodeling phase: This phase involves osteoclast resorption and osteoblastic formation of new bone matrix. These two processes are interconnected, but not occurring at the same site. As a result, unnecessary portions of the woven bone are absorbed, while necessary portions are strengthened, along the primary stress path of the bone. Ultimately, they are replaced by newly formed lamellar bone, recanalizing the medullary cavity and restoring the original bone structure and function.
Under conditions of complete anatomical reduction and absolute fixation, direct union between the fracture ends, also known as primary healing, occurs. Radiographs demonstrate the absence of external callus formation and the gradual disappearance of the fracture line. Direct healing requires close contact and absolute stability of the fracture ends. This relies on accurate anatomical reduction and absolute fixation with lag screws or compression plates. However, under a microscope, such perfect contact between the fracture interfaces is almost impossible; some areas are not fully aligned, resulting in tiny cavities between the contact surfaces (or possibly contact points). Therefore, histologically, direct healing can be divided into two types:
Interstitial healing: In stable gaps (<1 mm), blood vessels and primitive mesenchymal cells ingrow shortly after injury, and osteoblasts differentiate and proliferate within days, depositing osteoid on the fracture surface. In smaller gaps (150-200 μm), lamellar bone forms directly. In larger gaps, woven bone forms first and is eventually completely replaced by lamellar bone. The lamellar bone is remodeled and eventually reconstructed into normal bone tissue.
Contact healing: In the tightly contacted portion of the fracture ends, bone remodeling units can directly cross the fracture line without internal or external callus formation. In practice, under absolute fixation such as with compression plates, both gaps and contacts exist simultaneously, with the gap area being larger than the contact area. Therefore, gap healing constitutes the primary form of direct healing.
Under non-rigid fixation, fracture healing occurs similarly to the indirect healing mentioned earlier. Non-rigid fixation includes wire cerclage and tension band fixation, intramedullary nailing, external fixation, and some plates and screws that fail to achieve absolute fixation.
As previously stated, direct healing occurs within a 'stable' gap. However, under non-rigid fixation, 'micro-instability' exists within the fracture gap, meaning there is slight movement between the fracture ends, which can induce bone resorption and widen the fracture gap. This widened gap primarily achieves bony union through indirect healing. Widening of the fracture gap is sometimes very dangerous with conventional plate and screw fixation. The plates and screws themselves can obstruct contact between the fracture ends, preventing external force from passing through the fracture ends and concentrating on the plates and screws, ultimately leading to fatigue fracture or loosening. Relatively speaking, intramedullary nail fixation is beneficial for adjusting excessively wide gaps, maintaining the stability of the fracture ends, and allowing the affected limb to bear weight.