An osteoporosis bone defect regeneration strategy via three-dimension short fibers loaded with alendronate modified hydroxyapatite

Abstract

Osteoporotic bone defect has become clinic challenge due to its morbid bone microenvironment. Overactive bone resorption and limited bone formation lead to unstable combination between bone tissue and scaffolds. Electrospinning has been widely used in guide tissue membrane, but its barrier property results in limited application. In order to optimize the structure and add anti-bone resorption function of electrospinning fibers, we exploited the application of short fibers generated by homogenization at osteoporotic tibial bone defect. The modified nano-hydroxyapatite (m-HA) was loaded with alendronate. It overcame the problem that hydrophilic drugs were difficult to distribute uniformly in hydrophobic fibers. We confirmed that m-HA was loaded into polycaprolactone (PCL) short fibers. PCL short fibers with m-HA (PCL/m-HA) continuously released ALN, provided stable structure and showed good cytocompatibility. In vitro, PCL/m-HA increased the activity of alkaline phosphatase (ALP), promoted extracellular matrix mineralization and upregulated the expression of osteogenesis-related genes, Col 1, Alp, osteopontin (Opn) and runt-related transcription factor 2 (Runx2). In vivo, PCL/m-HA short fibers accelerated the new bone formation, inhibited the bone resorption and rebalanced the bone microenvironment through regulating osteoprotegerin (OPG) /receptor activator of NF-kB (RANKL) ratio. The above results confirmed that the PCL/m-HA short fibers achieved the application of three-dimension osteoporotic bone defect and had potential prospects in bone tissue scaffolds.