These results demonstrate the feasibility of creating a composite intervertebral disc with both anulusfibrosus and nucleus pulposus for clinical applications.

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This study evaluates the feasibility of producing a composite engineered tracheal equivalent composed of cylindrical cartilaginous structures with lumens lined with nasal epithelial cells. Chondrocytes and epithelial cells isolated from sheep nasal septum were cultured in Ham's F12 media. After 2 wk, chondrocyte suspensions were seeded onto a matrix of polyglycolic acid. Cell-polymer constructs were wrapped around silicon tubes and cultured in vitro for 1 wk, followed by implanting into subcutaneous pockets on the backs of nude mice. After 6 wk, epithelial cells were suspended in a hydrogel and injected into the embedded cartilaginous cylinders following removal of the silicon tube. Implants were harvested 4 wk later and analyzed. The morphology of implants resembles that of native sheep trachea. H&E staining shows the presence of mature cartilage and formation of a pseudo-stratified columnar epithelium, with a distinct interface between tissue-engineered cartilage and epithelium. Safranin-O staining shows that tissue-engineered cartilage is organized into lobules with round, angular lacunae, each containing a single chondrocyte. Proteoglycan and hydroxyproline contents are similar to native cartilage. This study demonstrates the feasibility of recreating the cartilage and epithelial portion of the trachea using tissue harvested in a single procedure. This has the potential to facilitate an autologous repair of segmental tracheal defects.

For successful tissue engineering, neovascularization of the implanted tissue is critical. Factors generated by endothelial cells are also considered crucial for the process of osteogenesis. The direct effects of supplementing tissue engineered constructs with cultured endothelial progenitor cells (EPCs) for enhancing bone regeneration have not been reported. In this study, we investigated the potential of EPCs to facilitate neovascularization in implants and evaluated their influence on bone regeneration. The influence of EPC soluble factors on osteogenic differentiation of mesenchymal stem cells (MSCs) was tested by adding EPC culture supernatant to MSC culture medium. To evaluate the influence of EPCs on MSC osteogenesis, canine MSCs-derived osteogenic cells and EPCs were seeded independently onto collagen fiber mesh scaffolds and co-transplanted to nude mice subcutaneously. Results from coimplant experiments were compared to implanted cells absent of EPCs 12 weeks after implantation. Factors from the culture supernatant of EPCs did not influence MSC differentiation. Coimplanted EPCs increased neovascularization and the capillary score was 1.6-fold higher as compared to the MSC only group (p < 0.05). Bone area was also greater in the MSC + EPC group (p < 0.05) and the bone thickness was 1.3-fold greater in the MSC + EPC group than the MSC only group (p < 0.05). These results suggest that soluble factors generated by EPCs may not facilitate the osteogenic differentiation of MSCs; however, newly formed vasculature may enhance regeneration of tissue-engineered bone.

PurposeIn stereotactic radiosurgery (SRS) with single‐isocentric treatments for brain metastases, rotational setup errors may cause considerable dosimetric effects. We assessed the dosimetric effects on HyperArc plans for single and multiple metastases.MethodsFor 29 patients (1–8 brain metastases), HyperArc plans with a prescription dose of 20–24 Gy for a dose that covers 95% (D95%) of the planning target volume (PTV) were retrospectively generated (Ref‐plan). Subsequently, the computed tomography (CT) used for the Ref‐plan and cone‐beam CT acquired during treatments (Rot‐CT) were registered. The HyperArc plans involving rotational setup errors (Rot‐plan) were generated by re‐calculating doses based on the Rot‐CT. The dosimetric parameters between the two plans were compared.ResultsThe dosimetric parameters [D99%, D95%, D1%, homogeneity index, and conformity index (CI)] for the single‐metastasis cases were comparable (P > 0.05), whereas the D95% for each PTV of the Rot‐plan decreased 10.8% on average, and the CI of the Rot‐plan was also significantly lower than that of the Ref‐plan (Ref‐plan vs Rot‐plan, 0.93 ± 0.02 vs 0.75 ± 0.14, P < 0.01) for the multiple‐metastases cases. In addition, for the multiple‐metastases cases, the Rot‐plan resulted in significantly higher V10Gy (P = 0.01), V12Gy (P = 0.02), V14Gy (P = 0.02), and V16Gy (P < 0.01) than those in the Ref‐plan.ConclusionThe rotational setup errors for multiple brain metastases cases caused non‐negligible underdosage for PTV and significant increases of V10Gy to V16Gy in SRS with HyperArc.

The aim of this work is to generate synthetic computed tomography (sCT) images from multi-sequence magnetic resonance (MR) images using an adversarial network and to assess the feasibility of sCT-based treatment planning for brain radiotherapy. Datasets for 15 patients with glioblastoma were selected and 580 pairs of CT and MR images were used. T1-weighted, T2-weighted and fluid-attenuated inversion recovery MR sequences were combined to create a three-channel image as input data. A conditional generative adversarial network (cGAN) was trained using image patches. The image quality was evaluated using voxel-wise mean absolute errors (MAEs) of the CT number. For the dosimetric evaluation, 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans were generated using the original CT set and recalculated using the sCT images. The isocenter dose and dose–volume parameters were compared for 3D-CRT and VMAT plans, respectively. The equivalent path length was also compared. The mean MAEs for the whole body, soft tissue and bone region were 108.1 ± 24.0, 38.9 ± 10.7 and 366.2 ± 62.0 hounsfield unit, respectively. The dosimetric evaluation revealed no significant difference in the isocenter dose for 3D-CRT plans. The differences in the dose received by 2% of the volume (D2%), D50% and D98% relative to the prescribed dose were &lt;1.0%. The overall equivalent path length was shorter than that for real CT by 0.6 ± 1.9 mm. A treatment planning study using generated sCT detected only small, clinically negligible differences. These findings demonstrated the feasibility of generating sCT images for MR-only radiotherapy from multi-sequence MR images using cGAN.

In the field of oral and maxillofacial surgery, tissue-engineering techniques have been found useful in regenerating lost tissues. Periodontal disease causes severe destruction of periodontal tissue, including the alveolar bone. In this study we attempted to regenerate canine periodontal tissue defects by grafting autologous cultured membrane derived from the periosteum. Under appropriate culture conditions, periosteal cells produce enough extracellular matrix to form sheets. Periosteum specimens were peeled from the mandibular body of adult hybrid dogs and were cultured until cells formed membrane. ALP activity was measured to determine an optimal time for grafting. The cultured periosteum (CP) was grafted and sutured on a mechanically made Class III furcation defect in the 4th mandibular premolars. After 3 months, the samples were harvested and observed radiologically and histologically. In cases of CP, the bone defects were regenerated and filled with newly formed hard tissue, whereas in the controls the defects remained. These results show that our novel treatment is effective in regenerating alveolar bone for the treatment of periodontal disease.