High-throughput organo-on-pillar (high-TOP) array system for three-dimensional ex vivo drug testing.

The development of organoid culture technologies has triggered industrial interest in ex vivo drug test-guided clinical response prediction for precision cancer therapy. The three-dimensional culture encapsulated with basement membrane (BM) components is extremely important in establishing ex vivo organoids and drug sensitivity tests because the BM components confer essential structures resembling tumor histopathology. Although numerous studies have demonstrated three-dimensional culture-based drug screening methods, establishing a large-scale drug-screening platform with matrix-encapsulated tumor cells is challenging because the arrangement of microspots of a matrix-cell droplet onto each well of a microwell plate is inconsistent and difficult to standardize. In addition, relatively low scales and lack of reproducibility discourage the application of three-dimensional organoid-based drug screening data for precision treatment or drug discovery. To overcome these limitations, we manufactured an automated organospotter-integrated high-throughput organo-on-pillar (high-TOP) drug-screening platform. Our system is compatible with various extracellular matrices, including BM extract, Matrigel, collagen, and hydrogel. In addition, it can be readily utilized for high-content analyses by simply exchanging the bottom plates without disrupting the domes. Our system demonstrated considerable robustness, consistency, reproducibility, and biological relevancy in three-dimensional drug sensitivity analyses using Matrigel-encapsulated ovarian cancer cell lines. We also demonstrated proof-of-concept cases representing the clinical feasibility of high-TOP-assisted ex vivo drug tests linked to clinical chemo-response in ovarian cancer patients. In conclusion, our platform provides an automated and standardized method for ex vivo drug-sensitivity-guided clinical response prediction, suggesting effective chemotherapy regimens for patients with cancer.

Level of surgical experience is associated with change in hip center of rotation following cementless total hip arthroplasty: A radiographic assessment.

OBJECTIVES: After total hip arthroplasty (THA), restoration of hip center of rotation (COR) is essential to ensure stability of the prosthetic hip and longevity of the prosthesis. Our aim was to determine whether, and how, the COR changed postoperatively compared to the native COR following implantation of a cementless acetabular component in anatomical position and to compare the accuracy of cup placement between two surgeons with different levels of surgical experience. MATERIALS AND METHODS: We evaluated 145 patients (145 hips) who underwent unilateral primary THA, who had no distorted acetabulum on the affected hip and a normal contralateral hip. Hip reconstruction was radiologically and clinically assessed at a minimum 2-year follow-up. Perioperative change in COR, initial cup position, offset, leg-length discrepancy (LLD), radiographic cup orientation, Harris Hip Score (HHS), component loosening, and dislocations were compared between the highly experienced surgeon and less-experienced surgeon groups. RESULTS: The COR was significantly displaced in the superior and medial directions postoperatively. Significant differences were identified in the vertical COR change, initial cup position, LLD, cup inclination, and cups within safe zones, but not in the horizontal COR change, offset parameters, cup anteversion, or HHS. There were no radiographic evidence of component loosening in both groups, but three dislocations (7%) only in the group operated on by the less-experienced surgeon (p = 0.027). CONCLUSIONS: We found that the postoperative COR tended to be displaced in the superior and medial directions, and that the level of surgical experience strongly affected the accuracy and consistency of cup placement, particularly in COR position and cup inclination.

Does size difference in allogeneic cancellous bone granules loaded with differentiated autologous cultured osteoblasts affect osteogenic potential?

We study the efficacy of bone regeneration by using two differently sized allogeneic cancellous bone granules loaded with autologous cultured osteoblasts in a rabbit model. Critical-sized bone defects of the radial shaft were made in 40 New Zealand White rabbits. Small allogeneic bone granules (150-300 µm in diameter) loaded with cultured differentiated autologous osteoblasts were implanted into one forearm (SBG group) and large bone granules (500-710 µm) loaded with osteoblasts were implanted into the forearm of the other side (LBG group). Radiographic evaluations were performed at 3, 6, 9 and 12 weeks and histology and micro-CT image analysis were carried out at 6 and 12 weeks post-implantation. On radiographic evaluation, the LBG group showed a higher bone quantity index at 3 and 6 weeks post-implantation (P < 0.05) but statistical significance was lost at 9 and 12 weeks. The progression of biological processes of the SBG group was faster than that of the LBG group. On micro-CT image analysis, the LBG group revealed a higher total bone volume and surface area than the SBG group at 6 weeks (P < 0.05) but the difference decreased at 12 weeks and was without statistical significance. Histological evaluation also revealed faster progression of new bone formation and maturation in the SBG group. Thus, the two differently sized allogeneic bone granules loaded with co-cultured autologous osteoblasts show no differences in the amount of bone regeneration, although the SBG group exhibits faster progression of bone regeneration and remodeling. This method might therefore provide benefits, such as a short healing time and easy application in an injectable form, in a clinical setting.