Multiple channels with interconnected pores in a bioceramic scaffold promote bone tissue formation

Abstract

Insufficient nutrition exchange and limited transportation of blood supply in a porous only scaffold often hinder bone formation, even though the porous scaffold is loaded with cells or growth factors. To overcome these issues, we developed a cell- and growth factor-free approach to induce bone formation in a critical-size bone defect by using an interconnected porous beta-tricalcium phosphate (β-TCP) scaffold with multiple channels. In vitro cell experimental results showed that multiple channels significantly promoted cell attachment and proliferation of human bone marrow mesenchymal stem cells, stimulated their alkaline phosphatase activity, and up-regulated the osteogenic gene expression. Multiple channels also considerably stimulated the expression of various mechanosensing markers of the cells, such as focal adhesion kinase, filamentous actin, and Yes-associated protein-1 at both static and dynamic culturing conditions. The in vivo bone defect implantation results demonstrated more bone formation inside multiple-channeled scaffolds compared to non-channeled scaffolds. Multiple channels prominently accelerated collagen type I, bone sialoprotein and osteocalcin protein expression. Fluorochrome images and angiogenic marker CD31 staining exhibited more mineral deposition and longer vasculature structures in multiple-channeled scaffolds, compared to non-channeled scaffolds. All the findings suggested that the creation of interconnected multiple channels in the porous β-TCP scaffold is a very promising approach to promote bone tissue regeneration.

Spatial-Controlled Coating of Pro-Angiogenic Proteins on 3D Porous Hydrogels Guides Endothelial Cell Behavior

“…For vascularization purposes, porous 3D hydrogels are widely employed due to their ability to facilitate nutrient and oxygen diffusion, thus enabling cell migration [ 21 , 22 ]. Additionally, the presence of channels within porous scaffolds has been reported to promote cell growth and rapid vascularization [ 23 , 24 ]. The channels in 3D hydrogels play a key role in guiding EC arrangement and should also be utilized to induce angiogenic behavior in ECs.…”

Bioactive Scaffolds as a Promising Alternative for Enhancing Critical-Size Bone Defect Regeneration in the Craniomaxillofacial Region

“…Suitable pore interconnectivity in scaffolds is an additional feature that enhances CSDs regeneration in vivo (Table ). Some examples that support this statement are (a) 3D-printed β-TCP scaffolds with pore diameters between 700 and 1,200 μm and connections between pores of 500–1,200 μm enhanced significantly the calvarial CSDs regeneration in rabbits compared to other patterns of pore size/connections; (b) when β-TCP scaffolds with interconnected pores were implanted into calvarial CSDs in rats, enhanced bone regrowth more efficiently, showing increased expression of components of the ECM and angiogenesis, than β-TCP scaffolds with not interconnected pores; (c) when PLLA/PCL porous scaffolds with two pore interconnectivity patterns of 0.5/0.8 or 0.5/1 mm (spacing and diameter of microchannels in mm, respectively) were grafted into rat CSDs, only the pattern of 0.5/0.8 showed increased angiogenesis and osteogenesis, compared to scaffolds with no interconnected pores or those with the alternate pattern of 0.5/1 mm; (d) BCP scaffolds with porous hexahedron channels, pore size of 400–700 μm, and a porosity of 95%, accelerated bone regrowth more efficiently than xenografts in rabbit calvarial CSDs; (e) mineralized Col scaffolds with interconnected pores enhanced cranial CSDs healing in skeletally immature sheep compared to scaffolds with no pores. Importantly, implantation of the collagen scaffolds with interconnected pores did not interfere with the overall skull growth, suggesting their suitability for implantation in children …”

“…One possibility to functionalize scaffolds is fabricating them with micromorphologies that mimic those observed on trabecular bone. Recently, the size and orientation of pores, their interconnectivity, the porosity (pores/volume), and particular arrangements of nanofibers or surface topography in scaffolds have been recognized as intrinsic osteoinductive cues. − Nevertheless, incorporating bioactive molecules or stem cells into scaffolds has been the most widely used approach to confer osteogenic abilities to scaffolds to date . Here, we first discuss the pros and cons of biomaterials that have been employed to fabricate scaffolds tested in vivo .…”

Structural and Functional Adaptive Artificial Bone: Materials, Fabrications, and Properties

“…Reproduced with permission. [ 9 ] Copyright 2021, Nature Publishing Group; nanoscale pore structure. Reproduced with permission.…”