Abstract
Osteoporosis is an age-related metabolic disease that results in limited bone regeneration capacity and excessive osteoclast activity. After arthroplasty in patients with osteoporosis, poor interface osseointegration resulting from insufficient bone regeneration ability often leads to catastrophic complications such as prosthesis displacement and loosening and periprosthetic fractures. In this study, we prepared a thermosensitive hydrogel loaded with bone morphogenetic protein-2 (BMP-2) to promote osteogenesis and osteoprotegerin (OPG) to inhibit excessive osteoclast activity. To construct three-dimensional (3D)-printed composite scaffolds for implantation, a hydrogel loaded with drugs was injected into porous Ti6Al4V scaffolds. The 3D-printed composite scaffolds showed good biocompatibility and sustained release of BMP-2 and OPG for more than 20 days. In vitro experiments indicated that composite scaffolds promoted osteogenic differentiation and reduced the osteoclastic activation simultaneously. Remarkably, immunofluorescence staining, micro-CT, histological, and biomechanical tests demonstrated that the sustained release of both BMP-2 and OPG from composite scaffolds significantly improved bone ingrowth and osseointegration in osteoporotic defects. In conclusion, this study demonstrated that the BMP-2- and OPG-loaded 3D-printed composite scaffolds can potentially promote osseointegration for osteoporotic patients after joint replacement.
Highlights
Osteoporosis is one of the most common metabolic skeletal diseases, and it is characterized by low bone strength, limited osteogenic activity, and enhanced osteoclast resorption, increasing the risk of bone fractures (Ferrari, 2018; Compston et al, 2019)
The poloxamer 407 hydrogel is widely used in bone tissue engineering because of its reversible thermo-responsive properties, superior drug delivery capabilities, excellent biocompatibility, and biodegradability (Yang et al, 2020)
The images of Calcein-AM/propidium iodide (PI) staining indicated that the OP-BMSCs had good cell viability in all groups on day 3 (Figure 2D). These results indicated that the incorporated drugs, hydrogels, and scaffolds used in this study had no cytotoxicity, suggesting that the bone morphogenetic protein-2 (BMP-2)/OPGloaded 3D-printed composite scaffolds had good biocompatibility and were suitable for in vivo applications
Summary
Osteoporosis is one of the most common metabolic skeletal diseases, and it is characterized by low bone strength, limited osteogenic activity, and enhanced osteoclast resorption, increasing the risk of bone fractures (Ferrari, 2018; Compston et al, 2019). The Ti6Al4V scaffold with optimized pore size and porosity is designed to match the bone tissue’s mechanical strength, minimizing the stress shielding We hypothesize that these BMP-2/OPG-loaded composite scaffolds will release drugs continuously and ameliorate the regenerating microenvironment in osteoporosis. Bioactive Bone Morphogenetic Protein-2 and Osteoprotegerin Release Profile To investigate the bioactive release of BMP-2 and OPG in vitro, the BMP-2/OPG-loaded 3D-printed composite scaffolds were put in a 24-well culture plate Real-Time Quantitative PCR After osteogenic induction culture of OP-BMSCs (1 × 105 cells/ well) in 24-well plates for 14 and 21 days, the expression of runtrelated transcription factor-2 (Runx-2), osteopontin (OPN), and receptor activator of NF-κB ligand (RANKL) were investigated using RT-qPCR. Implantation of 3D-Printed Composite Scaffolds Forty residual osteoporotic rabbits were enrolled in the osseointegration experiments, and they were randomly divided into five groups: S, SH, SH/BMP-2, SH/OPG, and SH/Dual. The statistical analyses were performed via Student’s t-test or one-way ANOVA, followed by the least significant difference test for multiple comparisons using SPSS 19.0 software (SPSS Inc., Chicago, IL, USA). p < 0.05 was deemed to indicate statistical significance
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