Hybrid composites of mesenchymal stem cell sheets, hydroxyapatite, and platelet-rich fibrin granules for bone regeneration in a rabbit calvarial critical-size defect model

Abstract

The reconstruction of large bone defects remains a major clinical challenge, and tissue engineering is a promising technique for resolving this problem. Many attempts have been made to optimize bone tissue engineering protocols. The aim of the present study was to develop a process incorporating mesenchymal stem cell (MSC) sheets with nanoscale hydroxyapatite (nano-HA) and autologous platelet-rich fibrin (PRF) granules for enhanced bone formation within a critical-sized rabbit cranial defect. MSC sheets and PRF were prepared prior to in vivo experiments. The osteogenic differentiation ability of MSCs and the ultrastructure of PRF were also studied. A total of 15 New Zealand white rabbits were used in the current study and critical-size defects (CSDs) were surgically introduced in the cranium (diameter, 15 mm). The surgical defects were treated with MSC/PRF composites, MSC composites or left empty. Animals were euthanized at week 8 post-surgery. Iconography, histological and histomorphometric analysis were performed to assess de novo bone formation. The percentage of new bone in the MSC/PRF group (35.7±5.1%) was significantly higher than that in the MSC (18.3±3.2%; P<0.05) and empty defect groups (4.7±1.5%; P<0.05). The results of the present study suggest that combined application of an MSC sheet with nano-HA and granular PRF enhances bone regeneration in a rabbit calvarial CSD model, and provides a novel insight into bone tissue regeneration for large bone defects.

Carrageenan enhances chondrogenesis and osteogenesis in human bone marrow stem cell culture

“…Applications of stem cells sheets are emerging as therapeutic strategies for the treatment of different injuries and pathophysiologies (Graceffa et al, 2018;Luo and Chen, 2018;Miyagawa et al, 2017;Pagani et al, 2003;Pellegrini et al, 1997;Sawa et al, 2012). Bone marrow mesenchymal stem cell (BMSC) sheets have been developed and characterised in vitro (Goldberg et al, 2017;See et al, 2010;Solorio et al, 2012) and assessed in pre-clinical models (Itokazu et al, 2016; www.ecmjournal.org Ma et al, 2017;Yano et al, 2013;Zou et al, 2009) for a wide range of clinical indications, including fat (Aubin et al, 2015;D'Andrea et al, 2008;Labbe et al, 2011;Vermette et al, 2007), bone (Geng et al, 2013;Goldberg et al, 2017;Ma et al, 2017;Wang et al, 2017;Zou et al, 2009) and cartilage (Ge et al, 2016;Itokazu et al, 2016;Qi et al, 2014;Solorio et al, 2012;Yano et al, 2013) tissue regeneration. However, due to slow and low level of ECM deposition, prolonged culture time is required to develop a scaffold-free implantable device [e.g.…”

Uptake of magnetic nanoparticles for adipose-derived stem cells with multiple passage numbers

“…We slowly added 25% (w/w) N(CH 3 ) 4 OH to a mixture of Fe 2+ and Fe 3+ (molar ratio is 1:2) until reaching a pH value of 13. This reaction was allowed to continue for 1 h to obtain black colloidal nanoparticles (Fe 3 O 4 ).…”

“…Stem cell-based therapy has shown great potential for the treatment of many conditions, such as neural lesions [2], immunological diseases [3] and bone defects [4]. However, in clinical practice, establishing the source of stem cells remains a challenge.…”

The use of bioactive factors to enhance bone regeneration: A narrative review

“…The combination of PRF with cell therapy has shown promising results. In particular, the addition of PRF to human‐cultured bone‐derived periosteal sheet (Horimizu, Kubota, Kawase, Nagata & Kobayashi, ) and the addition of PRF to sheets of MSCs or to a composite of MSCs and nanoscale HA (Wang et al., ; Wang, Li, Guo, et al., ) increased the amount of regenerated bone in calvarial CSDs. The combination of MSCs with an autologous platelet‐rich fibrin glue and GBR in dog mandibular defects was also associated with significant more bone regeneration in comparison to empty defects, defects treated with GBR or with a combination of MSCs and platelet‐rich fibrin glue at 16 weeks (Liao, Chen, Chen, Chen & Tsai, ).…”