Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering.

The efforts to grow mechanically functional cartilage from human mesenchymal stem cells have not been successful. We report that clinically sized pieces of human cartilage with physiologic stratification and biomechanics can be grown in vitro by recapitulating some aspects of the developmental process of mesenchymal condensation. By exposure to transforming growth factor-β, mesenchymal stem cells were induced to condense into cellular bodies, undergo chondrogenic differentiation, and form cartilagenous tissue, in a process designed to mimic mesenchymal condensation leading into chondrogenesis. We discovered that the condensed mesenchymal cell bodies (CMBs) formed in vitro set an outer boundary after 5 d of culture, as indicated by the expression of mesenchymal condensation genes and deposition of tenascin. Before setting of boundaries, the CMBs could be fused into homogenous cellular aggregates giving rise to well-differentiated and mechanically functional cartilage. We used the mesenchymal condensation and fusion of CMBs to grow centimeter-sized, anatomically shaped pieces of human articular cartilage over 5 wk of culture. For the first time to our knowledge biomechanical properties of cartilage derived from human mesenchymal cells were comparable to native cartilage, with the Young's modulus of >800 kPa and equilibrium friction coeffcient of <0.3. We also demonstrate that CMBs have capability to form mechanically strong cartilage-cartilage interface in an in vitro cartilage defect model. The CMBs, which acted as "lego-like" blocks of neocartilage, were capable of assembling into human cartilage with physiologic-like structure and mechanical properties.

Orthopedic surgery often requires bone grafts to correct large defects resulting from congenital defects, surgery or trauma. Great improvements have been made in tissue engineering of bone grafts. However, these grafts lack the vascularized component that is critical for their survival and function. From a clinical perspective, it would be ideal to engineer vascularized bone grafts starting from one single cell harvest obtained from the patient. To this end, we explored the potential of human adipose derived mesenchymal stem cells (hASC) as a single cell source for osteogenic and endothelial differentiation and the assembly of bone and vascular compartments within the same scaffold. hASC were encapsulated in fibrin hydrogel as a angioinductive material for vascular formation, combined with a porous silk fibroin sponge to support osteogenesis, and subjected to sequential application of growth factors. Three strategies were evaluated by changing spatio-temporal cues: 1) induction of osteogenesis prior to vasculogenesis, 2) induction of vasculogenesis prior to osteogenesis, or 3) simultaneous induction of osteogenesis and vasculogenesis. By 5 weeks of culture, bone-like tissue development was evidenced by the deposition of bone matrix proteins, alkaline phosphatase activity and calcium deposition, along with the formation of vascular networks evidenced by endothelial cell surface markers, such as CD31 and von Willebrand factor, and morphometric analysis. Most robust development of the two tissue compartments was achieved by sequential induction of osteogenesis followed by the induction of vasculogenesis. Taken together, the collected data strongly support the utility of hASC as a single cell source for the formation of vascularized bone tissue.

Public Health Service increased risk donor kidneys are discarded 50% more often than nonincreased risk donor kidneys despite equivalent patient and graft survival outcomes. Patient and provider biases as well as challenges in risk interpretation contribute to the underuse of increased risk donor organs. As the ultimate decision to accept or reject an increased risk donor organ results from the patient–provider conversation, there is an opportunity to improve this dialogue. This report introduces the best-case/worst-case communication guide for structuring high-stake conversations on increased risk kidney offers between transplant providers and their patients. Through best case/worst case, providers focus on eliciting patient values and long-term goals. The patient’s unique context can then inform an individualized discussion of “best,” “worst,” and “most likely” outcomes and support the provider’s ultimate recommendation. Transplant providers are encouraged to adopt this communication strategy to enhance shared decision-making and improve patient outcomes.

The aim of this study was to evaluate changes in 30-day postoperative outcomes and individual hospital variation in outcomes from 2012 to 2019 in a collaborative quality improvement network. Summary Background Data: Collaborative quality improvement efforts have been shown to improve postoperative outcomes overall; however, heterogeneity in improvement between participating hospitals remains unclear. Understanding the distribution of individual hospital-level changes is necessary to inform resource allocation and policy design. Methods: We performed a retrospective cohort study of 51 hospitals in the Michigan Surgical Quality Collaborative (MSQC) from 2012 to 2019. Risk-and reliability-adjusted hospital rates of 30-day mortality, complications, serious complications, emergency department (ED) visits, readmissions, and reoperations were calculated for each year and compared between the last 2 years and the first 2 years of the study period.Results: There was a significant decrease in the rates of all 5 adverse outcomes across MSQC hospitals from 2012 to 2019. Of the 51 individual hospitals, 31 (61%) hospitals achieved a decrease in mortality (range -1.3 percentage points to +0.6 percentage points), 40 (78%) achieved a decrease in complications (range -8.5 percentage points to +2.9 percentage points), 26 (51%) achieved a decrease in serious complications (range -3.2 percentage points to +3.0 percentage points), 29 (57%) achieved a decrease in ED visits (range 5.0 percentage points to +2.2 percentage points), 46 (90%) achieved a decrease in readmissions (range -3.1 percentage points to +0.4 percentage points) and 39 (76%) achieved a decrease in reoperations (range 3.3 percentage points to +1.0 percentage points). Conclusions: Despite overall improvement in surgical outcomes across hospitals participating in a quality improvement collaborative, there was substantial variation in improvement between hospitals, highlighting opportunities to better understand hospital-level barriers and facilitators to surgical quality improvement.