Mussel-inspired multifunctional surface through promoting osteogenesis and inhibiting osteoclastogenesis to facilitate bone regeneration

by Selleckchem | Oct 15 2023

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.

Comments:

The passage you provided describes a research study that aimed to develop a multifunctional bone repair scaffold for bone tissue engineering applications. The scaffold was designed to have dual therapeutic actions: promoting osteogenesis (bone formation) and inhibiting osteoclastogenesis (formation of bone-resorbing cells called osteoclasts). Here is a summary of the key points:

1. Surface coating process: The researchers used a surface coating technique inspired by mussel adhesive properties. They coated a biocompatible porous scaffold with polydopamine (PDA), which acted as an intermediate bridge for subsequent steps.

2. Immobilization of small-molecule activator: A small-molecule activator called LYN-1604 (LYN) was immobilized onto the PDA-coated scaffold surface. LYN specifically targeted osteoclast precursor cells, inhibiting their differentiation and functional activity.

3. In situ coprecipitation of hydroxyapatite nanocrystals: Hydroxyapatite (HA) nanocrystals, a mineral component of natural bone, were then coprecipitated onto the scaffold surface. HA provides biomineralization ability and enhances the scaffold's ability to promote bone regeneration.

4. Dual effects of the scaffold: The combination of LYN and HA resulted in a scaffold with both anti-osteoclastogenesis and pro-osteogenesis properties. This means that the scaffold inhibited the formation and activity of osteoclasts while stimulating bone formation.

5. Scaffold characteristics: The LYN/HA-coated hybrid scaffold had an interconnected porous structure with a nanoroughened surface topography. It exhibited favorable hydrophilicity (ability to attract water) and improved mechanical properties. The scaffold also demonstrated sustained release of LYN and calcium ions.

6. In vitro experiments: The scaffold showed good cytocompatibility, supporting cell adhesion, spreading, proliferation, alkaline phosphatase activity (an indicator of bone formation), matrix mineralization, and secretion of genes and proteins related to osteogenesis. It also stimulated the differentiation of endothelial cells involved in angiogenesis (formation of new blood vessels).

7. Inhibition of osteoclastogenesis: The scaffold effectively reduced osteoclastogenesis, as indicated by decreased tartrate-resistant acid phosphatase activity, reduced F-actin ring staining (a characteristic of mature osteoclasts), and suppressed secretion of genes and proteins related to osteoclast formation.

8. In vivo study: The LYN/HA-coated hybrid scaffold was tested in a rat calvarial defect model, where it significantly promoted bone repair and regeneration. Microcomputed tomography, histological analysis, and immunohistochemistry confirmed the scaffold's biosafety and its ability to induce osteogenesis while inhibiting osteoclastogenesis.

In conclusion, this study presents a promising strategy for developing multifunctional nanocomposite scaffolds that can simultaneously promote bone formation and inhibit bone resorption. The LYN/HA-coated hybrid scaffold demonstrated excellent potential for accelerating bone regeneration and could have significant implications in bone tissue engineering and regenerative medicine.