Acceleration of bone-defect repair by using A-W MGC loaded with BMP2 and triple point-mutant HIF1α-expressing BMSCs

Abstract

BackgroundThe goal of this study is to explore the effects of A-W MGC (apatite-wollastonite magnetic bioactive glass-ceramic) loaded with BMP2 (bone morphogenetic protein 2)- and HIF1αmu (hypoxia-inducible factor 1 mutation)-expressing BMSCs (bone marrow mesenchymal stem cells) on the bone defect repair.Methods(1) BMSCs were infected with viral solution containing BMP2 and HIF1αmu with the best MOI (multiplicity of infection). The efficiency was observed via hrGFP (human renilla reniformis green fluorescent protein). (2) The cells were divided into five groups (A–E), and ALP (alkaline phosphatase) activity was measured. (3) BMP2 and HIF1α (hypoxia-inducible factor 1α) protein were measured. (4) A-W MGC was loaded with BMSCs that contain the genes and implanted into the bone defect model. The animals were sacrificed 8 and 12 weeks later. (5) The healing was measured with X-ray, histology, and biomechanics.Results(1) BMSCs in A–D showed high transfection efficiency. (2) ALP in A and B was higher than the others (p = 0.041 or 0.038); A was higher than B (p = 0.038); (3) BMP2 in A and B was higher than the others (p = 0.014). HIF1α in A and C was higher than the others (p = 0.020). (4) 8 and 12 weeks after, an X-ray indicated that bone defect was nearly fully repaired in A and C. (5) 12 weeks after, the bone remodeling was complete in A and C. (6) The flexural strength in A and C was stronger than the others (p = 0.043).ConclusionEngineered A-W MGC with BMP2 and HIF1αmu-expressing BMSCs exhibits comparable therapeutic effects of bone-defect repair as an autologous bone graft.

Low intensity pulsed ultrasound promotes the migration of bone marrow- derived mesenchymal stem cells via activating FAK-ERK1/2 signalling pathway

“…Previous studies have shown that a series of specific molecules were released into the damaged area and enter the circulatory system when bones are damaged, and then the BMSCs from the injured tissue and the circulatory system migrated to the damaged site and differentiate into specific tissues [22]. BMSCs are directly involved in fracture healing [23]. To further explore whether the pretreatment of LIPUS will have beneficial effects on the migration of exogenous BMSCs to the bone defect area in vivo, this study successfully established an animal femoral defect model that could simulate fracture.…”

miR‐33a‐5p modulates TNF‐α‐inhibited osteogenic differentiation by targeting SATB2 expression in hBMSCs

“…Recombinant human bone morphogenetic protein (rhBMP)‐2 has been approved by the FDA for clinical applications due to its role in osteogenesis and angiogenesis during bone healing . Furthermore, it is often used in combination with seed cells such as BMSCs to maximize their capacity to accelerate osteogenesis at the site of a bone defect. However, several clinical studies of BMP‐2 have reported adverse inflammation‐related events and a low efficacy of BMP‐2 due to inflammation .…”

Innovative Options for Bone Metastasis Treatment: An Extensive Analysis on Biomaterials-Based Strategies for Orthopedic Surgeons

“…Fundamental aspects in this group of ceramics are firstly their “smart” capacity to adapt and modify their properties to the changing implant site environment, and secondly, a diverse handling method, mostly at room temperature, that allow the inclusion and preservation of bioactive molecules (drugs/antibiotics, growth factors, magnetic particles for thermal cancer therapy) ( Vallet-Regi et al, 2012 ; Comesaña et al, 2015 ; Koju et al, 2018 ; Vallet-Regí and Salinas, 2019 ). With the purpose to obtain enhanced therapeutic effectiveness, these materials were therefore tested in many studies as drug carriers or as gene delivery systems ( Ruiz-Hernández et al, 2008 ; Liu et al, 2009 ; Vallet-Regí and Ruiz-Hernández, 2011 ; Wu and Chang, 2014 ; Gao et al, 2015 ; Santos et al, 2017 ; Köse et al, 2018 ; Afewerki et al, 2020 ). To better resemble natural bone apatite and interact with neighbor tissues, synthetic HA can include several diverse ions in place of Ca 2+ , PO 4 3– , or OH – , e.g., Na + , K + , Mg 2+, Sr 2+ , Zn 2+ , Cl – , F – , HPO 4 2– ( Kim et al, 1998 ; Vallet-Regí and Arcos, 2005 ; Landi et al, 2007 , 2008 ; Kolmas et al, 2011 ; Bornapour et al, 2013 ; Montesi et al, 2017 ; Arcos and Vallet-Regí, 2020 ).…”