Clavicle Fracture Malunion Treated with an Osteotomy Guided by a Three-Dimensional-Printed Model: A Case Report.

CASE: This case report describes the management of a chronic and symptomatic clavicle malunion with use of a 3-dimensional (3D)-printed model during the preoperative surgical planning. CONCLUSION: The use of 3D printing has many applications in the medical field. Constant improvement in the quality of 3D printing has contributed to its increased use in a variety of surgeries. In our patient, 3D printing was used to generate a surface model of the clavicle fracture malunion and the "mirrored" contralateral healthy clavicle to plan an intraoperative osteotomy, which optimized the relative position of the osteotomy segments and hardware fixation.

Cytotoxicity of local anesthetics on human mesenchymal stem cells.

BACKGROUND: Local anesthetics are frequently delivered intra-articularly to provide perioperative pain control. Previous studies have shown that the commonly used drugs lidocaine, ropivacaine, and bupivacaine can be toxic to human chondrocytes. The present study was conducted to determine whether the toxic effects of local anesthetics on human chondrocytes also extend to human mesenchymal stem cells. METHODS: Human mesenchymal stem cells from three healthy donors were grown in tissue culture and exposed to the following anesthetic treatments for sixty minutes: (1) 1% lidocaine, (2) 2% lidocaine, (3) 0.25% bupivacaine, (4) 0.5% bupivacaine, (5) 0.2% ropivacaine, and (6) 0.5% ropivacaine. The cells were then allowed to recover for twenty-four hours in regular growth media, and viability was measured with use of fluorescent staining for live cells or a luminescence assay for ATP content. RESULTS: The live cell counts and ATP content were correlated (r2 = 0.79), and 2% lidocaine was found to be significantly more toxic than all doses of bupivacaine and ropivacaine. Treatment with 1% lidocaine resulted in significantly fewer live cells (49%) compared with the control, and the live cell count was also significantly less than that for the other anesthetics. However, the ATP level in the 1% lidocaine group was not significantly lower than those in the other groups. Bupivacaine and ropivacaine did not exhibit significant differences in toxicity compared with the control or with each other. CONCLUSIONS: Ropivacaine and bupivacaine had limited toxicity in human mesenchymal stem cells. However, lidocaine could significantly decrease mesenchymal stem cell viability. Since other studies have shown ropivacaine to be less toxic to chondrocytes than bupivacaine, ropivacaine may be a safer intra-articular anesthetic. CLINICAL RELEVANCE: Mesenchymal stem cells likely play a key role in healing following surgical procedures such as microfracture and ligament reconstruction. If local anesthetics are used following joint surgery, selection of an agent with low toxicity toward mesenchymal stem cells, such as ropivacaine, may maximize tissue healing potential.

Chondrocyte apoptosis after simulated intraarticular fracture: a comparison of histologic detection methods.

Accurate evaluation of programmed cell death, or apoptosis, in chondrocytes is essential to studying cartilage injury. We evaluated four methods of detecting chondrocyte-programmed cell death in formalin-fixed, paraffin-embedded cartilage after experimental osteochondral fracture. Human osteochondral explants were subjected to experimental fracture in a manner known to induce high levels of chondrocyte-programmed cell death. After 4 days in culture, specimens were fixed and analyzed for programmed cell death using: (1) terminal deoxynucleotidyl transferase end labeling; (2) DNA denaturation analysis using an antibody specific for single-stranded DNA; (3) immunohistochemistry using antisera specific for active caspase-3; and (4) in situ oligonucleotide ligation. Quantitative analysis of programmed cell death levels for each technique was performed comparing injured and uninjured areas of cartilage. We observed differences between injured and uninjured areas of cartilage using the four methods. Human cartilage fixed in zinc-formalin and embedded in paraffin is amenable to programmed cell death analysis using any of four independent methods, each of which ostensibly has some advantages in terms of assaying different steps along the apoptotic pathway. Using the protocols described in this article, investigators may have additional tools to identify and quantify chondrocytes undergoing programmed cell death after experimental cartilage injury.

Chondrocyte apoptosis: implications for osteochondral allograft transplantation.

Osteochondral allograft transplantation is a useful technique to manage larger articular cartilage injuries. One factor that may compromise the effectiveness of this procedure is chondrocyte cell death that occurs during the storage, preparation, and implantation of the osteochondral grafts. Loss of viable chondrocytes may negatively affect osteochondral edge integration and long-term function. A better understanding of the mechanisms responsible for chondrocyte loss could lead to interventions designed to decrease cell death and improve results. Recent studies indicate that apoptosis, or programmed cell death, is responsible for much of the chondrocyte death associated with osteochondral allograft transplantation. Theoretically, some of these cells can be rescued by blocking important apoptotic mediators. We review the role of apoptosis in cartilage degeneration, focusing on apoptosis associated with osteochondral transplantation. We also review the pathways thought to be responsible for regulating chondrocyte apoptosis, as well as experiments testing inhibitors of the apoptotic pathway. These data suggest that key contributors to the apoptotic process can be manipulated to enhance chondrocyte survival. This knowledge may lead to better surgical outcomes for osteochondral transplantation.

Comparison of chondrocyte apoptosis in vivo and in vitro following acute osteochondral injury.

The objective of the present study was to directly compare levels of chondrocyte apoptosis produced by osteochondral injury in vivo and in vitro. Adult New Zealand White rabbits underwent 2 mm osteochondral drilling of the medial and lateral femoral condyles of a single hind limb. Animals were euthanized, and specimens were harvested at 0, 2, 4, 7, 10, and 14 days following injury. At the time of euthanasia, identical injuries were created in the femoral condyles of the contralateral hind limb. These condyles were maintained in vitro under standard tissue culture conditions until harvesting at time points corresponding to the in vivo specimens (i.e. after 0, 2, 4, 7, 10 and 14 days in culture). The extent of apoptosis in the in vivo and in vitro specimens was quantified by TUNEL analysis. The amount and distribution of TUNEL positive cells followed similar patterns in both in vivo and in vitro specimens with a maximal percentage of apoptotic chondrocytes observed on post-injury day 4. On post-injury day 4, in vivo specimens displayed a statistically significant increased overall level of apoptosis compared to in vitro specimens [in vivo=32.5+/-8.6%; in vitro=22.2+/-4.8%; (p=0.03)]. These experiments suggest that the majority of programmed cell death observed after osteochondral injury can be attributed to processes intrinsic to the cartilage itself; however, additional factors present within the acutely traumatized joint also appear to potentiate chondrocyte apoptosis following injury.