A porcine calvaria defect study was carried out to investigate the bone repair potential of three-dimensional (3D)-printed poly-ε-caprolactone (PCL) scaffolds embedded with nanoporous PCL. A microscopic grid network was created by rapid prototyping making a 3D-fused deposition model (FDM-PCL). Afterward, the FDM-PCL scaffolds were infused with a mixture of PCL, water, and 1,4-dioxane and underwent a thermal-induced phase separation (TIPS) followed by lyophilization. The TIPS process lead to a nanoporous structure shielded by the printed microstructure (NSP-PCL). Sixteen Landrace pigs were divided into two groups with 8 and 12 weeks follow-up, respectively. A total of six nonpenetrating holes were drilled in the calvaria of each animal. The size of the cylindrical defects was h 10 mm and Ø 10 mm. The defects were distributed randomly using following groups: (a) NSP-PCL scaffold, (b) FDM-PCL scaffold, (c) autograft, (d) empty defect, (a1) NSP-PCL scaffold + autologous mononuclear cells, and (a2) NSP-PCL scaffold + bone morphogenetic protein 2. Bone volume to total volume was analyzed using microcomputed tomography (µCT) and histomorphometry. The µCT and histological data showed significantly less bone formation in the NSP-PCL scaffolds in all three variations after both 8 and 12 weeks compared to all other groups. The positive autograft control had significantly higher new bone formation compared to all other groups except the FDM-PCL when analyzed using histomorphometry. The NSP-PCL scaffolds were heavily infiltrated with foreign body giant cells suggesting an inflammatory response and perhaps active resorption of the scaffold material. The unmodified FDM-PCL scaffold showed good osteoconductivity and osseointegration after both 8 and 12 weeks.

We tested the hypothesis that erythropoietin (EPO) enhances bone formation after posterolateral spinal fusion (PLF) in a rabbit model. Thirty-four adult rabbits underwent posterolateral intertransverse arthrodesis at the L5-L6 level using 2.0 g autograft per side. The animals were randomly divided into two groups receiving subcutaneous daily injections of either EPO or saline for 20 days. Treatment commenced 2 days preoperatively. Hemoglobin was monitored at baseline and 2, 4, and 6 weeks after fusion surgery. After euthanasia 6 weeks postoperatively, manual palpation, radiographic, and histomorphometric examinations were performed. Bone volume of the fusion mass was estimated by CT after 6 weeks. EPO increased bone fusion volume to 3.85 ccm (3.66-4.05) compared with 3.26 ccm (2.97-3.55) in the control group (p < 0.01). EPO treatment improved vascularization of the fusion mass and increased hemoglobin levels (p < 0.01). Fusion rate tended to be higher in the EPO group based on manual palpation, CT, and radiographic examinations. For the first time EPO has shown to augment bone formation after autograft PLF in a rabbit model. Increased vascularization provides a partial explanation for the efficacy of EPO as a bone autograft enhancer.

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Stem cell and hydrogel therapy is able to partly regenerate IDD and maintain perfusion and permeability of the vertebral endplate and subchondral bone. Dynamic contrast-enhanced MRI may become an important tool in future investigation of the vertebral endplate.

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f Traditionally, the pharmacokinetics of antimicrobials in bone have been investigated using bone biopsy specimens, but this approach suffers from considerable methodological limitations. Consequently, new methods are needed. The objectives of this study were to assess the feasibility of microdialysis (MD) for measuring cefuroxime in bone and to obtain pharmacokinetic profiles for the same drug in porcine cortical and cancellous bone. The measurements were conducted in bone wax sealed and unsealed drill holes in cortical bone and in drill holes in cancellous bone and in subcutaneous tissue. As a reference, the free and total plasma concentrations were also measured. The animals received a bolus of 1,500 mg cefuroxime over 30 min. No significant differences were found between the key pharmacokinetic parameters for sealed and unsealed drill holes in cortical bone. The mean ؎ standard error of the mean area under the concentration-time curve (AUC) values from 0 to 5 h were 6,013 ؎ 1,339, 3,222 ؎ 1086, 2,232 ؎ 635, and 952 ؎ 290 min · g/ml for free plasma, subcutaneous tissue, cancellous bone, and cortical bone, respectively (P < 0.01, analysis of variance). The AUC for cortical bone was also significantly different from that for cancellous bone (P ‫؍‬ 0.04). This heterogeneous tissue distribution was also reflected in other key pharmacokinetic parameters. This study validates MD as a suitable method for measuring cefuroxime in bone. Cefuroxime penetration was impaired for all tissues, and bone may not be considered one distinct compartment.

PET and MRI are valid tools for monitoring the process of interbody fusion in vivo. Osteogenic mechanisms using COLLOSS E resembles that of autograft by the process of endochondral ossification. rhBMP-2 deposits osteoid directly on the collagen network.

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