Abstract
BackgroundSegmental bone defects caused by trauma, tumors, or infection are a serious challenge for orthopedists in the world. Recent developments in tissue engineering have provided a new treatment for segmental bone defects. Urine-derived stem cells (USCs) can be obtained noninvasively and might be a new kind of seed cells used in bone tissue regeneration. Therefore, the first aim of the present study was to investigate the biological characteristics of USCs. The second aim of the present study was to study the osteogenic effect of surface mineralized biphasic calcium phosphate ceramics (BCPs) loaded with USCs in vitro and in vivo.MethodsWe isolated USCs from the urine of healthy adult donors and evaluated the biological characteristics of USCs in vitro. We mineralized the surface of BCPs by simulated body fluid (SBF). Cell adhesion and proliferation of USCs on the surface mineralized BCPs were evaluated. Osteogenic proteins and genes of USCs on the surface mineralized BCPs were texted by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) assay. Critical-sized segmental bone defects model in New Zealand white rabbits were established and randomly divided into 4 groups (surface mineralized BCPs loaded with USCs, BCPs loaded with USCs, surface mineralized BCPs, and BCPs) based on the implant they received. The therapeutic efficacy of the scaffolds in a large bone defect at post-implantation was evaluated by imaging and histological examination.ResultsUSCs isolated in our study expressed stem cell-specific phenotypes and had a stable proliferative capacity and multipotential differentiation capability. Surface mineralized BCPs promoted osteogenic proteins and genes expression of USCs without affecting the proliferation of USCs. After 10 weeks, the amount of new bone formation was the highest in the group of surface mineralized BCPs loaded with USCs.ConclusionUSCs, from non-invasive sources, have good application prospects in the field of bone tissue engineering. Surface mineralized BCPs can significantly enhance osteogenic potential of USCs without changing biological characteristics of BCPs. Surface mineralized BCPs loaded with USCs are effective in repairing of critical-sized segmental bone defects in rabbits.
Highlights
Segmental bone defects caused by trauma, tumors, or infection are a serious challenge for orthopedists in the world
The alkaline phosphatase (ALP) content of group of surface mineralized biphasic calcium phosphate ceramics (BCPs) loaded with Urine-derived stem cells (USCs) on day 3, day 7, day 14 was 13.28 ± 2.13 U/L, 15.68 ± 1.43 U/L, and 15.08 ± 1.64 U/L, respectively, which were significantly higher
Compared to the group of BCPs loaded with USCs, the gene expression levels of ALP, RUNX2, bone morphogenetic protein-2 (BMP2), and OCN in the group of surface mineralized BCPs loaded with USCs were significantly higher on days 7 and 14 (Fig. 8)
Summary
Segmental bone defects caused by trauma, tumors, or infection are a serious challenge for orthopedists in the world. Recent developments in tissue engineering have provided a new treatment for segmental bone defects. Urine-derived stem cells (USCs) can be obtained noninvasively and might be a new kind of seed cells used in bone tissue regeneration. Many researchers have confirmed that USCs possess self-renewal ability and might be a new kind of seed cells used in bone regeneration [3,4,5]. As USCs can be obtained by noninvasive means, they represent a promising alternative kind of seed cells for bone regeneration [6]. There are few studies focusing on the scaffolds loaded with USCs used in repair of segmental bone defects. It is not clear bone repair effect of scaffolds loaded with USCs in vivo
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