An injectable self-adaptive polymer as a drug carrier for the treatment of nontraumatic early-stage osteonecrosis of the femoral head

可注射自适应聚合物作为药物载体用于治疗非创伤性早期股骨头坏死

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作者:Ning Kong #, Hang Yang #, Run Tian #, Guanzhi Liu, Yiyang Li, Huanshuai Guan, Qilu Wei, Xueshan Du, Yutian Lei, Zhe Li, Ruomu Cao, Yiwei Zhao, Xiaohui Wang, Kunzheng Wang, Pei Yang

Abstract

Core decompression (CD) with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head (ONFH). Adjuvant treatments are widely used in combination with CD as suitable methods of therapy. Existing augmentations have to be fabricated in advance. Here, we report a novel injectable glycerin-modified polycaprolactone (GPCL) that can adapt to the shape of the CD cavity. GPCL shows great flowability at 52.6 °C. After solidification, its compressive modulus was 120 kPa at body temperature (37 °C). This excellent characteristic enables the polymer to provide mechanical support in vivo. In addition, GPCL acts as a carrier of the therapeutic agent zoledronic acid (ZA), demonstrating sustained release into the CD region. ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases. Compared to that in the CD group, CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head. At the interface between the GPCL and CD tunnel wall, osteogenesis was significantly promoted. In addition, morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance. These results suggest a strategy effective to preserve the bone density of the femoral head, thus decreasing the possibility of femoral head collapse. This novel injectable polymer has, therefore, considerable potential in clinical applications.

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