Prior to transplantation, mesenchymal stem/stromal cells (MSCs) can be induced toward the osteoblastic phenotype using a cocktail of soluble supplements. However, there is little evidence of differentiated MSCs directly participating in bone formation, suggesting that MSCs may either die or revert in phenotype upon transplantation. Cell-secreted decellularized extracellular matrices (DMs) are a promising platform to confer bioactivity and direct cell fate through the presentation of a complex and physiologically relevant milieu. Therefore, we examined the capacity of biomimetic DMs to preserve the mineral-producing phenotype upon withdrawal of the induction stimulus. Regardless of induction duration, ranging up to 6 weeks, MSCs exhibited up to a 5-fold reduction in osteogenic markers within 24 hours following stimulus withdrawal. We show that seeding osteogenically induced MSCs on DMs yields up to 2-fold more calcium deposition than tissue culture plastic, and this improvement is at least partially mediated by increasing actin cytoskeletal tension via the ROCK II pathway. MSCs on DMs also secreted 25% more vascular endothelial growth factor (VEGF), a crucial endogenous proangiogenic factor that is abrogated during MSC osteogenic differentiation. The deployment of DMs into a subcutaneous ectopic site enhanced the persistence of MSCs 5-fold, vessel density 3-fold, and bone formation 2-fold more than MSCs delivered without DMs. These results underscore the need for deploying MSCs using biomaterial platforms such as DMs to preserve the in vitro-acquired mineral-producing phenotype and accelerate the process of bone repair.

OBJECTIVEPreoperative depression has been linked to a variety of adverse outcomes following lumbar fusion, including increased pain, disability, and 30-day readmission rates. The goal of the present study was to determine whether preoperative depression is associated with increased narcotic use following lumbar fusion. Moreover, the authors examined the association between preoperative depression and a variety of secondary quality indicator and economic outcomes, including complications, 30-day readmissions, revision surgeries, likelihood of discharge home, and 1- and 2-year costs.METHODSA retrospective analysis was conducted using a national longitudinal administrative database (MarketScan) containing diagnostic and reimbursement data on patients with a variety of private insurance providers and Medicare for the period from 2007 to 2014. Multivariable logistic and negative binomial regressions were performed to assess the relationship between preoperative depression and the primary postoperative opioid use outcomes while controlling for demographic, comorbidity, and preoperative prescription drug–use variables. Logistic and log-linear regressions were also used to evaluate the association between depression and the secondary outcomes of complications, 30-day readmissions, revisions, likelihood of discharge home, and 1- and 2-year costs.RESULTSThe authors identified 60,597 patients who had undergone lumbar fusion and met the study inclusion criteria, 4985 of whom also had a preoperative diagnosis of depression and 21,905 of whom had a diagnosis of spondylolisthesis at the time of surgery. A preoperative depression diagnosis was associated with increased cumulative opioid use (β = 0.25, p < 0.001), an increased risk of chronic use (OR 1.28, 95% CI 1.17–1.40), and a decreased probability of opioid cessation (OR 0.96, 95% CI 0.95–0.98) following lumbar fusion. In terms of secondary outcomes, preoperative depression was also associated with a slightly increased risk of complications (OR 1.14, 95% CI 1.03–1.25), revision fusions (OR 1.15, 95% CI 1.05–1.26), and 30-day readmissions (OR 1.19, 95% CI 1.04–1.36), although it was not significantly associated with the probability of discharge to home (OR 0.92, 95% CI 0.84–1.01). Preoperative depression also resulted in increased costs at 1 (β = 0.06, p < 0.001) and 2 (β = 0.09, p < 0.001) years postoperatively.CONCLUSIONSAlthough these findings must be interpreted in the context of the limitations inherent to retrospective studies utilizing administrative data, they provide additional evidence for the link between a preoperative diagnosis of depression and adverse outcomes, particularly increased opioid use, following lumbar fusion.

Level II, systematic review.

3.

Several aspects of the design and reporting of RCTs on neurosurgical procedures have improved over time. Better powered and accurately reported trials are needed in neurosurgery to deliver evidence-based care and achieve optimal outcomes.