Bone fractures create five problems that must be resolved: bleeding, risk of infection, hypoxia, disproportionate strain, and inability to bear weight. There have been enormous advancements in our understanding of the molecular mechanisms that resolve these problems after fractures, and in best clinical practices of repairing fractures. We put forth a modern, comprehensive model of fracture repair that synthesizes the literature on the biology and biomechanics of fracture repair to address the primary problems of fractures. This updated model is a framework for both fracture management and future studies aimed at understanding and treating this complex process. This model is based upon the fracture acute phase response (APR), which encompasses the molecular mechanisms that respond to injury. The APR is divided into sequential stages of “survival” and “repair.” Early in convalescence, during “survival,” bleeding and infection are resolved by collaborative efforts of the hemostatic and inflammatory pathways. Later, in “repair,” avascular and biomechanically insufficient bone is replaced by a variable combination of intramembranous and endochondral ossification. Progression to repair cannot occur until survival has been ensured. A disproportionate APR—either insufficient or exuberant—leads to complications of survival (hemorrhage, thrombosis, systemic inflammatory response syndrome, infection, death) and/or repair (delayed- or non-union). The type of ossification utilized for fracture repair is dependent on the relative amounts of strain and vascularity in the fracture microenvironment, but any failure along this process can disrupt or delay fracture healing and result in a similar non-union. Therefore, incomplete understanding of the principles herein can result in mismanagement of fracture care or application of hardware that interferes with fracture repair. This unifying model of fracture repair not only informs clinicians how their interventions fit within the framework of normal biological healing but also instructs investigators about the critical variables and outputs to assess during a study of fracture repair.

Superficial siderosis (SS) of the CNS is a rare disease caused by repeated hemorrhages in the subarachnoid space. The subsequent deposition of hemosiderin in the brain and spinal cord leads to the progression of neurological deficits. The causes of bleeding include prior intradural surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. Recently, surgical treatment of SS associated with dural defect has been reported. The authors of the present report describe 2 surgically treated SS cases and review the literature on surgically treated SS. The patients had dural defects with fluid-filled collections in the spinal canal. In both cases, the dural defects were successfully closed, and the fluid collection was resolved postoperatively. In one case, the neurological symptoms did not progress postoperatively. In the other case, the patient had long history of SS, and the clinical manifestations partially deteriorated after surgery, despite the successful dural closure. In previously reported surgically treated cases, the dural defects were closed by sutures, patches, fibrin glue, or muscle/fat grafting. Regardless of the closing method, dural defect closure has been shown to stop CSF leakage and subarachnoid hemorrhaging. Successfully repairing the defect can halt the disease progression in most cases and may improve the symptoms that are associated with CSF hypovolemia. However, the effect of the dural closure may be limited in patients with long histories of SS because of the irreversibility of the neural tissue damage caused by hemosiderin deposition. In patients with SS, it is important to diagnose and repair the dural defect early to minimize the neurological impairments that are associated with dural defects.

Osteomyelitis remains one of the most challenging disorders for orthopedic doctors despite the advancement of therapeutic techniques. The purpose of this study was to investigate the feasibility of local antibiotic administration using hydroxyapatite/collagen (HAp/Col) as a drug delivery system. We hypothesized that higher adsorbability of antibiotics onto HAp/Col will result in more efficacious activity and therefore, treatment of osteomyelitis. Eight antibiotics were examined in this study: amikacin, cefazolin, cefotiam, daptomycin, minocycline, piperacillin, teicoplanin, and vancomycin. Aligning with their adsorbability onto HAp/Col, minocycline, teicoplanin, and vancomycin showed antibacterial effects up to 14 days after subcutaneous implantation in Wistar rats; while antibiotics with reduced adsorbability (cefazolin, cefotiam, piperacillin) had diminished antibacterial effects. Furthermore, when implanted into a rat femur, vancomycin levels from the Hap/Col were detected in the medullary space above the minimum inhibitory concentration for Staphylococcus aureus for 7 days, while cefazolin levels were undetectable. Aligning with these results, implantation of Hap/Col impregnated with vancomycin to the femur in an acute osteomyelitis rat model had a greater therapeutic effect than cefazolin, as measured by the number of bacteria, the extent of bone destruction, and bone regeneration. These results indicated that the adsorbability of antibiotics onto their carrier is important when locally administered and that HAp/Col scaffolds might be a useful antibiotic delivery system for osteomyelitis. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:843‐851, 2020

No abstract