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With a gradually increasing elderly population, the treatment of geriatric patients represents a major challenge for trauma and reconstructive surgery. Although, it is well established that aging affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we investigated fracture healing in young adult (3–4 months) and aged (16–18 months) CD-1 mice using a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks after fracture, the analysis showed no significant difference in bending stiffness between the two study groups. Additional histological analysis showed a delayed endochondral ossification in aged animals as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when compared to young adult animals. However, the overall healing capacity of the fractured femora was not affected by aging.

Non-union formation represents a major complication in trauma surgery. Adequate vascularization has been recognized as vital for bone healing. However, the role of vascularization in the pathophysiology of non-union formation remains elusive. This is due to difficulties in studying bone microcirculation in vivo. Therefore, we herein studied in a murine osteotomy model whether photoacoustic imaging may be used to analyze vascularization in bone healing and non-union formation. We found that oxygen saturation within the callus tissue is significantly lower in non-unions compared to unions and further declines over time. Moreover, the amount of total hemoglobin (HbT) within the callus tissue was markedly reduced in non-unions. Correlation analyses showed a strong positive correlation between microvessel density and HbT, indicating that photoacoustically determined HbT is a valid parameter to assess vascularization during bone healing. In summary, photoacoustic imaging is a promising approach to study vascular function and tissue oxygenation in bone regeneration.

Porous polyethylene (pPE) is a commonly used biomaterial in craniofacial reconstructive surgery. However, implant failure due to insufficient vascularization represents a major issue. To overcome this problem, we herein introduce an effective strategy to improve the vascularization and incorporation of pPE. Adipose tissue-derived microvascular fragments (MVF) from transgenic green fluorescent protein (GFP)+ mice were suspended in platelet-rich plasma (PRP) for the coating of pPE. PRP/MVF-coated pPE as well as PRP-coated and uncoated controls were subsequently implanted into the dorsal skinfold chamber and the flanks of GFP- wild-type mice to analyze their in vivo performance throughout 2, 4 and 8 weeks by means of intravital fluorescence microscopy, histology and immunohistochemistry. The GFP+/GFP- cross-over design allowed the identification of GFP+ MVF within the implants. Shortly after implantation, they rapidly reassembled into new blood-perfused microvascular networks, resulting in a significantly accelerated vascularization of PRP/MVF-coated pPE when compared to both controls. The overall numbers of rolling and adherent leukocytes within the microcirculation as well as macrophages, multi-nucleated giant cells and mast cells around the implants did not differ between the three groups. However, in contrast to uncoated controls, PRP/MVF-coated and PRP-coated pPE promoted pro-angiogenic M2 macrophage polarization at the implantation site. These findings demonstrate that PRP/MVF-coating represents a highly effective strategy to enhance the vascularization, biocompatibility and tissue incorporation of pPE. STATEMENT OF SIGNIFICANCE: The clinical in vivo performance of implanted biomaterials is crucially dependent on their adequate incorporation into the body. To achieve this, we herein introduce an effective biological coating strategy. Our results demonstrate that coating with PRP and MVF accelerates and enhances the vascularization, biocompatibility and tissue incorporation of porous polyethylene. Because this type of biological coating is easily applicable on any type of biomaterial, our approach may rapidly be translated into clinical practice to improve the outcome of various regenerative approaches.