Hu, Michael S.

Introduction: Over 500,000 bone grafting procedures are performed every year in the United States for neoplastic and traumatic lesions of the craniofacial skeleton, costing $585 million in medical care. Current bone grafting procedures are limited, and full-thickness critical-sized defects (CSDs) of the adult human skull thus pose a substantial reconstructive challenge for the craniofacial surgeon. Cell-based strategies have been shown to safely and efficaciously accelerate the rate of bone formation in CSDs in animals. The authors recently demonstrated that supraphysiological transplantation of macrophages seeded in pullalan–collagen composite hydrogels significantly accelerated wound healing in wild type and diabetic mice, an effect mediated in part by enhancing angiogenesis. In this study, the authors investigated the bone healing effects of macrophage transplantation into CSDs of mice. Methods: CD1 athymic nude mice (60 days of age) were anesthetized, and unilateral full-thickness critical-sized (4 mm in diameter) cranial defects were created in the right parietal bone, avoiding cranial sutures. Macrophages were isolated from FVB-L2G mice and seeded onto hydroxyapatite-poly (lactic-co-glycolic acid) (HA-PLGA) scaffolds (1.0 × 106 cells per CSD). Scaffolds were incubated for 24 hours before they were placed into the CSDs. Macrophage survival was assessed using three-dimensional in vivo imaging system (3D IVIS)/micro-CT. Micro-CT at 0, 2, 4, 6, and 8 weeks was performed to evaluate gross bone formation, which was quantified using Adobe Photoshop. Microscopic evidence of bone regeneration was assessed at 8 weeks by histology. Bone formation and macrophage survival were compared at each time point using independent samples t tests. Results: Transplantation of macrophages at supraphysiological concentration had no effect on the formation of bones in CSDs as assessed by either micro-CT data at any time point analyzed (all P > 0.05). These results were corroborated by histology. 3D IVIS/micro-CT demonstrated survival of macrophages through 8 weeks. Conclusion: Supraphysiologic delivery of macrophages to CSDs of mice had no effect on bone formation despite survival of transplanted macrophages through to 8 weeks posttransplantation. Further research into the physiological effects of macrophages on bone regeneration is needed to assess whether recapitulation of these conditions in macrophage-based therapy can promote the healing of large cranial defects.

The risks of systemic anti-coagulation or its reversal are well known but accepted as necessary under certain circumstances. However, particularly in the plastic surgical patient, systemic alteration to hemostasis is often unnecessary when local therapy could provide the needed adjustments. The aim of this review was to provide a summarized overview of the clinical applications of topical anti- and pro-coagulant therapy in plastic and reconstructive surgery. While not a robust field as of yet, local tranexamic acid (TXA) has shown promise in achieving hemostasis under various circumstances, hemostats are widely used to halt bleeding, and local anticoagulants such as heparin can improve flap survival. The main challenge to the advancement of local therapy is drug delivery. However, with increasingly promising innovations underway, the field will hopefully expand to the betterment of patient care.