Stem cell therapy for improved fixation of cementless total hip replacements

描述(申请人提供)：通过现代外科技术的进步，全髋关节置换术(THR)已经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手术的惊人数量(仅在美国就有200,000例)导致每年数千例植入失败。大多数种植体失败的原因是无菌松动和种植体不稳定。早期的植入物设计使用了合成骨水泥，这种骨水泥可以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被用于大部分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“压入”骨中来实现固定。因此，足够的骨长入对患者的康复至关重要。羟基磷灰石等材料加速了骨的生长，但这些涂层可能会由于降解而促进骨溶解。作为替代，骨髓间充质干细胞(BMSCs)可能被用于促进骨形成的治疗。目前的方法利用体外骨髓间充质干细胞培养，这造成了几个实际和监管方面的挑战。作为替代，我们已经开发出具有高特异性和亲和力的结合BMSCs的多肽。我们的目标是将这些多肽包裹在髋关节植入物上，以便从植入物的骨髓丰富的环境中捕获BMSCs，并将它们捕获到植入物表面。在初步研究中，我们已经证明干细胞培养中的矿化依赖于细胞浓度。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快患者的康复进程，并改善非骨水泥种植体的短期临床结果。

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.