Accelerating the pace of discovery in orthopaedic research: A vision toward team science.

The landscape of basic science in the United States and around the world is changing, and the field of orthopaedic research is positioned to lead by embracing a culture of collaborative, team science that reflects our field's interdisciplinary nature. In this article we hope to address some of the cultural challenges and programmatic barriers that impede a team science approach in the US and suggest opportunities for change. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1673-1679, 2016.

Growth, differentiation capacity, and function of mesenchymal stem cells expanded in serum-free medium developed via combinatorial screening.

The presence of serum in cell culture medium presents an obstacle to safe and efficient production of hMSCs for therapeutic purposes. Availability of defined medium will be crucial to elucidating the mechanism of action of hMSCs in many indications as well as a prerequisite to consistently produce cells with predictable performance characteristics. Using a bioinformatics driven approach, which we call the BD Discovery Platform, we have developed a novel serum-free medium that supports highly efficient growth while maintaining the surface markers and functional characteristics defining hMSCs. In a comparison with serum-containing and other commercially available serum-free formulations, all conditions led to expansion of cells that meet the minimal criteria for hMSCs as set by the International Society for Cellular Therapy (ISCT). However, differences in growth characteristics and gene expression patterns suggest that expansion in serum-free growth conditions can provide greater yields in a shorter time. The mRNA expression profile observed in cells grown without serum suggests upregulation of several genes implicated in hMSC function as well as downregulation of the proinflammatory cytokine IL6.

The introduction of an extracellular matrix-based scaffold to the marketplace.

Continuous application of new scientific knowledge is a central characteristic of modern medical practice. The current pace of medical innovation creates an environment of rapid change, and the introduction of innovative treatments in the area of regenerative medicine in orthopaedics prompts health care providers, medical device companies, patient advocacy groups, and health insurance payors to study the most optimal method for introducing these treatments to clinical practice. Questions regarding the role and value of preclinical testing, clinical trials, and postmarketing surveillance are pertinent to this discussion, and answers to these questions should culminate in a strategy that benefits patient care.

Efficacy of mesenchymal stem cell enriched grafts in an ovine posterolateral lumbar spine model.

STUDY DESIGN: Four groups of 6 animals underwent single-level noninstrumented posterolateral lumbar fusion (PLF) with one of the following grafts: 1) autograft, 2) cell-enriched beta-tricalcium phosphate (TCP), 3) TCP with whole bone marrow, and 4) TCP alone. Plain radiographs were taken after surgery and at death, 6 months after surgery. Explanted spine segments were analyzed by manual palpation, micro-CT, and histology. OBJECTIVE: A sheep spine fusion study was undertaken to evaluate the healing performance of a TCP graft enriched with osteoprogenitor cells using Selective Cell Retention technology (SCR), compared with autograft, TCP with whole bone marrow, and TCP alone. SUMMARY OF BACKGROUND DATA: Improved bone healing with previously demonstrated using grafts enriched in osteoprogenitor cells. METHODS: Cell-enriched grafts were obtained by processing 30 mL of bone marrow through 10 mL of TCP. TCP was also used either saturated with bone marrow or alone. RESULTS: At 6 months, 33% of the SCR-enriched TCP and 25% of the autograft sites were fused, compared with 8% of the TCP plus whole bone marrow and 0% of the TCP alone. Histology of fused samples showed denser bone formation in the SCR-enriched TCP grafts than in the autograft sites. CONCLUSIONS: The use of SCR-enriched TCP and autograft resulted in similar fusion rates in an ovine posterolateral noninstrumented lumbar spine fusion model.

Bone grafts prepared with selective cell retention technology heal canine segmental defects as effectively as autograft.

Using a canine critical-size segmental defect model, a two-phased study was undertaken to evaluate the healing efficacy of demineralized bone and cancellous chips (DBM-CC) enriched with osteoprogenitor cells using a Selective Cell Retention (SCR) technology. The goals of this study were: 1) to determine the bone-healing efficacy of SCR-enriched grafts versus autograft, and 2) to assess the value of clotting SCR-enriched grafts with platelet-rich plasma (PRP). Thirty dogs were included in Phase I: 18 dogs were treated with an SCR-enriched DBM-CC graft clotted with autologous bone marrow, and were compared to 12 autograft controls. In Phase II, 24 animals were divided into 4 groups of 6 animals, each treated with a different bone graft material: 1) iliac crest autograft, 2) DBM-CC alone, 3) DBM-CC saturated with marrow, and 4) SCR-enriched DBM-CC clotted with PRP. All grafts were placed unilaterally in a 21-mm long osteoperiosteal femoral, instrumented, critical-size defect. Radiographs were obtained for all animals postoperatively and every 4-16 weeks; animals were then sacrificed. All femurs were prepared for histology. Femurs in the Phase II study were also analyzed by micro-CT. At 16 weeks, healing--defined by bridging bone across the defects--was observed in 50% of the DBM-CC alone group and 67% of the DBM-CC saturated with marrow group; 100% of the autograft and SCR-enriched DBM-CC groups were healed. Histologically, grafts clotted with PRP showed more mature bone than those implanted with autologous bone, which in turn were similar to those implanted with bone marrow clotted SCR-enriched grafts. These results demonstrated that: 1) SCR-enriched DBM-CC was equivalent to autograft to repair critical-size defects, and 2) while not statistically significant, PRP may have accelerated bone maturation when used to clot osteoprogenitor-enriched DBM-CC grafts--as compared to cell-enriched, DBM-CC grafts without PRP--in large animal models.