Background: Although strong efforts have been made over the last decade to introduce stem cell and tissue engineering treatment strategies to the field of orthopaedics, only few clinical applications are currently available. Materials and Methods: The clinical outcomes of ten patients with volumetric bone deficiencies treated with mesenchymal stem cells and bone marrow aspirate are presented in this case series. Results were evaluated with radiographs. In addition to the in vivo data, we also presented in vitro data of BMC cultivated onto a porous collagen I scaffold and the technique of bone marrow aspiration via a comerically available system. Results: Our results demonstrated that there is a rationale for a clinical application of BMC / bone aspirate in the treatment of osseous defects. The intraoperative harvest procedure is a safe method and does not significantly prolong the time of surgery. In addition, MSC isolated from the aspirate was able to adhere and proliferate onto a collagen scaffold in significant numbers after a 15 min incubation period. These cells were then able to allow osteogenic differentiation in vitro without any osteogenic stimuli. Conclusions: The local application of BMC / bone aspirate in the treatment of bone deficiencies may be a promising alternative to autogenous bone grafting and help reduce donor site morbidity.

The surface design of titanium implants influences not only the local biological reactions but also affects at least the clinical result in orthopaedic application. During the last decades, strong efforts have been made to improve osteointegration and prevent bacterial adhesion to these surfaces. Following the rule of “smaller, faster, cheaper”, nanotechnology has encountered clinical application. It is evident that the hierarchical implant surface micro- and nanotopography orchestrate the biological cascades of early peri-implant endosseous healing or implant loosening. This review of the literature gives a brief overview of nanostructured titanium-base biomaterials designed to improve osteointegration and prevent from bacterial infection.

Stem cell and tissue engineering—based therapies have become a promising option to heal bony defects in the future. Human cord blood—derived mesenchymal stem cells were seeded onto a collagen/tricalcium phosphate scaffold and xenotransplanted into critical size femoral defects of 46 nude rats. We found a survival of human cells within the scaffold and surrounding bone/bone marrow up to 4 wk after transplantation and an increased bone healing rate compared with controls without stem cells. This study supports the application of cord blood stem cells for bone regeneration. Introduction: The treatment of critical size bone defects is still a challenging problem in orthopedics. In this study, the survival, migration, and bone healing promoting potency of cord blood—derived stem cells were elucidated after xenotransplantation into a critical size femoral defect in athymic nude rats. Materials and Methods: Unrestricted somatic stem cells (USSCs) isolated from human cord blood were tested toward their mesenchymal in vitro potency and cultivated onto a collagen I/III and β-tricalcium phosphate (β-TCP) scaffold. The biomaterial-USSC composite was transplanted into a 4-mm femoral defect of 40 nude rats and stabilized by an external fixator. Twelve animals without USSCs served as controls. Cell survival, migration, and bone formation were evaluated by blood samples, X-rays, and histological and immunocytochemical analysis of different organs within a maximal postoperative follow-up of 10 wk. Results: Of the 52 nude rats, 46 animals were evaluated (drop-out rate: 11.5%). Human-derived stem cells showed an engraftment within the scaffold and adjacent femur up to 4 wk after xenotransplantation. With further time, the human cells were destroyed by the host organism. We found a significant increase in bone formation in the study group compared with controls. USSC transplantation did not significantly influence blood count or body weight in athymic nude rats. Whereas the collagen I/III scaffold was almost resorbed 10 wk after transplantation, there were still significant amounts of TCP present in transplantation sites at this time. Conclusions: Human cord blood—derived stem cells showed significant engraftment in bone marrow, survived within a collagen-TCP scaffold up to 4 wk, and increased local bone formation in a nude rat's femoral defect.

Introduction: Bone marrow oedema (BME) and avascular osteonecrosis (AVN) are disorders of unclear origin. Although there are numerous operative and non-operative treatments for AVN, pain management in patients with AVN remains challenging. Prostaglandins play an important role in inflammatory responses and cell differentiation. It is thought that prostaglandin I₂ ([PGI₂] or synonoma prostacyclin) and its analogues promote bone regeneration on a cellular or systemic level. The purpose of this study was to assess the curative and symptomatic efficacy of the prostacyclin analogue iloprost in BME and AVN patients. Method: We are reporting on 50 patients (117 bones) affected by BME/AVN who were treated with iloprost. Pain levels before, during and 3 and 6 months after iloprost application were evaluated by a visual analogue scale (VAS). The short form(SF)-36 health survey served to judge general health status before and after treatment. Harris Hip Score (HHS) and Knee Society Score (KSS) were performed as functional scores and MRI and X-rays before and 3 and 6 months after iloprost application served as objective parameters for morphological changes of the affected bones. Results: We found a significant improvement in pain, functional and radiological outcome in BME and early AVN stages after iloprost application, whereas patients with advanced AVN stages did not benefit from iloprost infusions. Mean pain level decreased from 5.26 (day 0) to 1.63 (6 months) and both HHS and KSS increased during follow-up. Moreover, the SF-36 increased from 353.2 (day 0) to 560.5 points (6 months). We found a significant decrease in BME on MRI scans after iloprost application. Conclusions: In addition to other drugs, iloprost may be an alternative substance which should be considered in the treatment of BME/AVN-associated pain.

Dexamethasone/ascorbic acid/glycerolphosphate (DAG) and bone morphogenic protein (BMP)‐2 are potent agents in cell proliferation and differentiation pathways. This study investigates the in vitro interactions between dexamethasone and BMP‐2 for an osteoblastic differentiation of mesenchymal stem cells (MSCs). Bone marrow‐derived human MSCs were cultured with DAG (group A), BMP‐2 + DAG (group B), and DAG + BMP‐2 combined with a porous collagen I/III scaffold (group C). RT‐PCR, ELISA, immuncytochemical stainings and flow cytometry analysis served to evaluate the osteogenic‐promoting potency of each of the above conditions in terms of cell morphology/viability, antigen presentation, and gene expression. DAG induced collagen I secretion from MSCs, which was further increased by the combination of DAG + BMP‐2. In comparison, the collagen scaffold and the control samples showed no significant influence on collagen I secretion of MSCs. DAG stimulation of MSCs led also to a steady but not significant increase of BMP‐2 level. A DAG and more, a DAG + BMP‐2, stimulation increased the number of mesenchymal cells (CD105+/CD73+). All samples showed mRNA of ALP, osteopontin, Runx2, Twist 1 and 2, Notch‐1/2, osteonectin, osteocalcin, BSP, and collagen‐A1 after 28 days of in vitro culture. Culture media of all samples showed a decrease in Ca²⁺and POconcentration, whereas a collagen‐I‐peak only occurred at day 28 in DAG‐ and DAG + BMP‐2‐stimulated bone marrow cells. In conclusion, BMP‐2 enhances DAG‐induced osteogenic differentiation in mesenchymal bone marrow cells. Both agents interact in various ways and can modify osteoblastic bone formation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1440–1448, 2008