A Biomimetic Macroporous Hybrid Scaffold with Sustained Drug Delivery for Enhanced Bone Regeneration

Abstract

Bone regeneration is a highly complex physiological process regulated by several factors. In particular, bone-mimicking extracellular matrix and available osteogenic growth factors such as bone morphogenetic protein (BMP) have been regarded as key contributors for bone regeneration. In this study, we developed a biomimetic hybrid scaffold (CEGH) with sustained release of BMP-2 that would result in enhanced bone formation. This hybrid scaffold, composed of BMP-2-loaded cryoelectrospun poly(εcaprolactone) (PCL) (CE) surrounded by a macroporous gelatin/ heparin cryogel (GH), is designed to overcome the drawbacks of the relatively weak mechanical properties of cryogels and poor biocompatibility and hydrophobicity of electrospun PCL. The GH component of the hybrid scaffold provides a hydrophilic surface to improve the biological response of the cells, while the CE component increases the mechanical strength of the scaffold to provide enhanced mechanical support for the defect area and a stable environment for osteogenic differentiation. After analyzing characteristics of the hybrid scaffold such as hydrophilicity, pore difference, mechanical properties, and surface charge, we confirmed that the hybrid scaffold shows enhanced cell proliferation rate and apatite formation in simulated body fluid. Then, we evaluated drug release kinetics of CEGH and confirmed the sustained release of BMP-2. Finally, the enhanced osteogenic differentiation of CEGH with sustained release of BMP-2 was confirmed by Alizarin Red S staining and real-time PCR analysis.

Silicon Nitride, a Bioceramic for Bone Tissue Engineering: A Reinforced Cryogel System With Antibiofilm and Osteogenic Effects

“…A higher stiffness of SiN-GC scaffolds due to SiN incorporation is more likely to induce osteogenic differentiation than GC, which has relatively low mechanical stiffness, a known limitation of such hydrogels ( Slaughter et al, 2009 ). The low mechanical stiffness of the scaffold is not favorable for osteogenic differentiation, since the stiffness of the scaffold affects the cell signaling and focal adhesions that would lead cells to differentiate into a tissue that has a similar stiffness to the scaffold ( Engler et al, 2006 ; Bose et al, 2012 ; Oh et al, 2016 ; Lee et al, 2021b ). Therefore, SiN reinforcement in SiN-GC increased the elastic modulus which would increase focal adhesions, cell proliferation, and osteogenic differentiation for bone tissue regeneration and enhanced mechanical support for the defect area ( Figure 2E ) ( Nam et al, 2011 ; Chen et al, 2015 ).…”

“…Along with this, the increasing number of bone fractures and orthopedic-related injuries due to an exponential growth of the elderly population has prompted researchers to explore bone tissue engineering to address these issues ( Bose et al, 2012 ; Gong et al, 2015 ; Longoni et al, 2018 ). Many therapeutic strategies have been suggested to promote bone regeneration, including scaffolds ( Lin et al, 2019 ; Zhang et al, 2019 ; Zhou et al, 2019 ), stem cells ( Annamalai et al, 2019 ; Kim et al, 2019 ; Kim et al, 2020 ), and osteogenic factors ( Naskar et al, 2017 ; Lee et al, 2020 ; Amirthalingam et al, 2021 ; Lee et al, 2021b ). More recently, biomaterial scaffolds that can promote bone tissue repair on their own, without the need for delivering cells, have emerged as a potentially powerful paradigm for bone tissue engineering, due to their promising advantages of reduced cost and fewer translational barriers than other regenerative medicine strategies, such as cell-based therapy ( Christman, 2019 ; Montoya et al, 2021 ).…”

Exosome-functionalized magnesium-organic framework-based scaffolds with osteogenic, angiogenic and anti-inflammatory properties for accelerated bone regeneration

“…The surface of the PLGA scaffold was smooth and uniform, but after Mg-GA MOF addition, the fibrous membrane became rougher, and lumpy materials were observed. A high porosity is an essential prerequisite for effective bone substitute materials [ 44 ], and scaffolds with an optimal pore size facilitate bone in-growth and neovascularization [ 45 , 46 ]. The addition of Mg-GA MOF made the composite scaffolds suitable for use as a bone graft.…”

Development of a Polysaccharide-Based Hydrogel Drug Delivery System (DDS): An Update

“…Cryogelation, particulate leaching, lyophilization, gas foaming, additive manufacturing (3D printing), freeze-thawing, and microgel assembly methods have been used to fabricate macroporous hydrogels. These techniques generally avoid harmful chemical agents or high temperatures, making macroporous hydrogels ideal to mimic the extracellular matrix (ECM) of native tissues [32,33]. Most recently, lyophilized macroporous D-galactose-based hydrogels exhibited a pore size ranging from 4 to 20 µm and the sustained release of gentamicin (hydrophilic drug) up to 92% within 72 h [34].…”