No abstract

Many regenerative medicine applications seek to harness the biologic power of stem cells in architecturally complex scaffolds or microenvironments. Traditional tissue engineering methods cannot create such intricate structures, nor can they precisely control cellular position or spatial distribution. These limitations have spurred advances in the field of bioprinting, aimed to satisfy these structural and compositional demands. Bioprinting can be defined as the programmed deposition of cells or other biologics, often with accompanying biomaterials. In this concise review, we focus on recent advances in stem cell bioprinting, including performance, utility, and applications in regenerative medicine. More specifically, this review explores the capability of bioprinting to direct stem cell fate, engineer tissue(s), and create functional vascular networks. Furthermore, the unique challenges and concerns related to bioprinting living stem cells, such as viability and maintaining multi- or pluripotency, are discussed. The regenerative capacity of stem cells, when combined with the structural/compositional control afforded by bioprinting, provides a unique and powerful tool to address the complex demands of tissue engineering and regenerative medicine applications.

Purpose To determine if automated continuous distraction osteogenesis at rates > 1mm/day would result in clinical and radiographic bone formation in a minipig model. Materials and Methods An automated, continuous, curvilinear distraction device was placed across a mandibular osteotomy in 10 minipigs. After 12 mm of distraction and 24 days fixation, animals were sacrificed and bone healing evaluated. The continuous distraction rates were 1.5 (n=5) and 3 mm/day (n=5). A semiquantitative scale was used to assess ex-vivo clinical appearance of the distraction gap (3= osteotomy not visible; 2= <50%; 1= >50%; 0= 100% visible); stability (3 = no mobility; 2 and 1 = mobility in 2 or 1 plane respectively; 0= mobility in 3 planes); radiographic density (4 = 100% gap opaque, 3= >75%, 2 = 50% – 75%, 1= <50%, or 0 = radiolucent). Groups of 4 minipigs distracted discontinuously at 1, 2, and 4 mm/day served as controls. Results The continuous DO 1.5 mm/day group had significantly higher scores for appearance and radiographic density compared to the discontinuous 4 mm/day group. The continuous DO 3mm/day group had significantly higher scores for appearance and radiographic density compared to the discontinuous 4 mm/day group, and higher stability compared to the discontinuous 2 and 4 mm/day groups. Conclusions Results of this preliminary study indicate that continuous DO at rates of 1.5 and 3.0 mm/day produces better bone formation when compared to discontinuous DO at rates faster than 1mm/day.

The purpose of this study was to demonstrate that automated, continuous, curvilinear distraction osteogenesis (DO) in a minipig model is effective when performed bilaterally, at rates up to 3mm/day, to achieve clinically relevant lengthening. A Yucatan minipig in the mixed dentition phase, underwent bilateral, continuous DO at a rate of 2 mm/day at the center of rotation; 1.0 and 3.0 mm/day at the superior and inferior regions, respectively. The distraction period was 13 days with no latency period. Vector and rate of distraction were remotely monitored without radiographs, using the device sensor. After fixation and euthanasia, the mandible and digastric muscles were harvested. The ex-vivo appearance, stability, and radiodensity of the regenerate were evaluated using a semi-quantitative scale. Percent surface area (PSA) occupied by bone, fibrous tissue, cartilage, and hematoma were calculated using histomorphometrics. The effects of DO on the digastric muscles and mandibular condyles were assessed via microscopy and degenerative changes were quantified. The animal was distracted to 21 mm and 24 mm on the right and left sides, respectively. Clinical appearance, stability, and radiodensity were scored as ‘3’ bilaterally indicating osseous union. The total PSA occupied by bone (right = 75.53±2.19%; left PSA = 73.11±2.18%) approached that of an unoperated mandible (84.67±0.86%). Digastric muscles and condyles showed negligible degenerative or abnormal histologic changes. This proof of principle study is the first report of osseous healing with no ill-effect on associated soft tissue and the mandibular condyle using bilateral, automated, continuous, curvilinear DO at rates up to 3 mm/day. The model approximates potential human application of continuous automated distraction with a semiburied device.