Dual actions of osteoclastic-inhibition and osteogenic-stimulation through strontium-releasing bioactive nanoscale cement imply biomaterial-enabled osteoporosis therapy
“… 61 A higher level of OCN expression was observed in the 15 and 25m-HANFs/GelMA groups than in the other groups, which is thought to be associated with the osteoblastic populations of these two groups having better maturation and differentiation properties. 62 , 63 Figure 11 Immunohistochemical staining of Runx2, Col1a1, and OCN (brown). Scale bar: 50 μm.…”
Purpose
Methacrylic anhydride-modified gelatin (GelMA) hydrogels exhibit many beneficial biological features and are widely studied for bone tissue regeneration. However, deficiencies in the mechanical strength, osteogenic factors and mineral ions limit their application in bone defect regeneration. Incorporation of inorganic fillers into GelMA to improve its mechanical properties and bone regenerative ability has been one of the research hotspots.
Methods
In this work, hydroxyapatite nanofibers (HANFs) were prepared and mineralized in a simulated body fluid to make their components and structure more similar to those of natural bone apatite, and then different amounts of mineralized HANFs (m-HANFs) were incorporated into the GelMA hydrogel to form m-HANFs/GelMA composite hydrogels. The physicochemical properties, biocompatibility and bone regenerative ability of m-HANFs/GelMA were determined in vitro and in vivo.
Results
The results indicated that m-HANFs with high aspect ratio presented rough and porous surfaces coated with bone-like apatite crystals. The incorporation of biomimetic m-HANFs improved the biocompatibility, mechanical, swelling, degradation and bone regenerative performances of GelMA. However, the improvement in the performance of the composite hydrogel did not continuously increase as the amount of added m-HANFs increased, and the 15m-HANFs/GelMA group exhibited the best swelling and degradation performances and the best bone repair effect in vivo among all the groups.
Conclusion
The biomimetic m-HANFs/GelMA composite hydrogel can provide a novel option for bone tissue engineering in the future; however, it needs further investigations to optimize the proportions of m-HANFs and GelMA for improving the bone repair effect.
“… 61 A higher level of OCN expression was observed in the 15 and 25m-HANFs/GelMA groups than in the other groups, which is thought to be associated with the osteoblastic populations of these two groups having better maturation and differentiation properties. 62 , 63 Figure 11 Immunohistochemical staining of Runx2, Col1a1, and OCN (brown). Scale bar: 50 μm.…”
Purpose
Methacrylic anhydride-modified gelatin (GelMA) hydrogels exhibit many beneficial biological features and are widely studied for bone tissue regeneration. However, deficiencies in the mechanical strength, osteogenic factors and mineral ions limit their application in bone defect regeneration. Incorporation of inorganic fillers into GelMA to improve its mechanical properties and bone regenerative ability has been one of the research hotspots.
Methods
In this work, hydroxyapatite nanofibers (HANFs) were prepared and mineralized in a simulated body fluid to make their components and structure more similar to those of natural bone apatite, and then different amounts of mineralized HANFs (m-HANFs) were incorporated into the GelMA hydrogel to form m-HANFs/GelMA composite hydrogels. The physicochemical properties, biocompatibility and bone regenerative ability of m-HANFs/GelMA were determined in vitro and in vivo.
Results
The results indicated that m-HANFs with high aspect ratio presented rough and porous surfaces coated with bone-like apatite crystals. The incorporation of biomimetic m-HANFs improved the biocompatibility, mechanical, swelling, degradation and bone regenerative performances of GelMA. However, the improvement in the performance of the composite hydrogel did not continuously increase as the amount of added m-HANFs increased, and the 15m-HANFs/GelMA group exhibited the best swelling and degradation performances and the best bone repair effect in vivo among all the groups.
Conclusion
The biomimetic m-HANFs/GelMA composite hydrogel can provide a novel option for bone tissue engineering in the future; however, it needs further investigations to optimize the proportions of m-HANFs and GelMA for improving the bone repair effect.
“…With this volume of water, all pellets could be completely submerged in a 15 cm 3 conical tube. The tubes were sealed and incubated at 37 °C, in adherence to an earlier protocol [ 71 ]. To assess the cumulative ion release, the elute media was collected progressively at different time points (1, 3, 7, 14, 21 days) and the solution was regularly refreshed [ 40 ].…”
“…Osteoclast-related bone resorption may be a pivotal factor contributing to unsatisfactory bone repair efficacy. Recently, accumulating evidence has proven that osteoclasts play an indispensable role in bone formation, maintenance, and remodeling 11 . In addition, studies have pointed out that osteoclasts can resorb the bone matrix during bone metabolism and further release active transforming growth factor-β1 (TGF-β1) to recruit MSCs and induce osteogenesis 12 .…”
Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.
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