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

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

doi:10.1038/s41413-022-00196-y

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.

Highlights

Osteonecrosis of the femoral head (ONFH) is a devastating disease that causes extreme pain and disability
The degradation of PCL is autocatalyzed by the carboxylic acid group that is liberated during hydrolysis, in addition to the action of a b
Sections of the different organs were evaluated, and the results demonstrated that the implanted materials and their degradation products caused no morphologic changes at the organ level (Fig. S4)

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is a devastating disease that causes extreme pain and disability. This condition is bilateral in more than 60% of patients.[1]. Those suffering from this condition are mostly young or middle aged.[2]. In the US, more than 20 000 individuals are afflicted by ONFH annually, the prevalence of which continues to increase.[3,4]. In China, it has been estimated that more than 8 million individuals cumulatively have suffered from ONFH.[5]. The incidence of ONFH has been reported to be 1.4 per 100 000 in the UK, which is close to that reported for Japan (1.9 per 100 000).[6]. ONFH patients suffer from both physical discomfort and severe mental pressure during social activities.[7]

Methods

Results

Conclusion