Stem cell therapy for improved fixation of cementless total hip replacements

描述（由申请人提供）：通过现代外科进步，全髋关节置换术（THR）已成为迄今为止最成功的植入手术之一。尽管长期成功率很高，但每年THR手术的数量惊人（仅在美国就有约20万例），导致每年数千例植入失败。大多数植入物因无菌性松动和植入物不稳定而失效。早期的植入物设计使用合成骨水泥，其引起局部炎症反应并刺激骨吸收。作为回应，医生转向非骨水泥植入物-特别是在活跃的年轻患者中-这种植入物设计现在用于大多数THR手术。 与骨水泥型植入物不同，非骨水泥型植入物通过将多孔钛“压配”到骨中实现固定。因此，充分的骨长入对于患者恢复至关重要。诸如羟基磷灰石的材料加速骨长入，但这些涂层可能由于降解而促进骨质溶解。作为替代方案，骨髓来源的间充质干细胞（BMSC）可用作促进骨形成的治疗。目前的方法利用离体BMSC培养，这产生了几个实际和监管挑战。作为替代方案，我们已经开发了以高特异性和亲和力结合BMSC的肽。我们的目标是将这些肽包被到髋关节植入物上，以便从植入物富含骨髓的环境中捕获BMSC并将其捕获到植入物表面。在初步研究中，我们已经证明，在干细胞培养矿化是依赖于细胞浓度。因此，我们假设将骨髓间充质干细胞集中在钛种植体上将加速患者的恢复过程，并改善非骨水泥种植体的短期临床结局。

DESCRIPTION (provided by applicant): Through modern surgical advancements, total hip replacements (THR) have become one of the most successful implant procedures to date. Even though long-term success rates are high, the staggering number of THR procedures per annum (~200,000 in the United States alone) results in thousands of failed implants each year. Most implants fail through aseptic loosening and implant instability. Earlier implant designs utilized synthetic bone cements that elicited a localized inflammatory response and stimulated bone resorption. In response, physicians shifted towards cementless implants-especially in active younger patients-and this implant design is now used in a majority of THR procedures. Unlike cemented implants, cementless implants achieve fixation by "press-fitting" porous titanium into bone. As such, adequate bone ingrowth is critical for patient recovery. Materials such as hydroxyapatite hasten bone ingrowth, but these coatings may promote osteolysis due to degradation. As an alternative, bone marrow- derived mesenchymal stem cells (BMSCs) may be used as a treatment to promote bone formation. Current methods utilize ex vivo BMSC culture that creates several practical and regulatory challenges. As an alternative, we have developed peptides that bind BMSCs with high specificity and affinity. Our goal is to coat these peptides onto hip implants in order to capture BMSCs from the implant's marrow-rich surroundings and capture them onto the implant surface. In preliminary studies, we have demonstrated that mineralization in stem cell cultures is dependent on cell concentration. Thus, we hypothesize that concentrating BMSCs on titanium implants will speed the patient recovery process and improve short-term clinical outcomes for cementless implants.