Bioinspired Redwood‐Like Scaffolds Coordinated by In Situ‐Generated Silica‐Containing Hybrid Nanocoatings Promote Angiogenesis and Osteogenesis both In Vitro and In Vivo

Abstract

Inspired by natural redwood and bone, a biomimetic strategy is presented to develop a highly bioactive redwood-like nanocomposite via radial freeze casting of biocompatible hydrogels followed by the in situ coprecipitation of a Si-containing CaP hybrid nanocoating (SCPN). The engineered material displays radially aligned macrochannels and a porous network structure similar to those of natural redwood. In addition to acting as a mechanical reinforcement, introducing SCPNs into the weak redwood-like scaffold yields not only a nanoroughened surface topography, a low swelling ratio, retarded enzymatic degradation, and enhanced protein absorption abilities but also the sustained sequential release of Si and Ca ions, thereby providing essential biophysical and biochemical cues for effective bone regeneration. Benefiting from the redwood-like structures and bioactive SCPNs, the biomimetic materials create a favorable microenvironment for promoting the initial adhesion, spreading, proliferation, and migration of bone marrow-derived mesenchymal stem cells and human umbilical vein endothelial cells. Furthermore, the in vitro and in vivo data showed that the biocompatible redwood-like scaffold with precipitated SCPN can synergistically promote osteogenesis and angiogenesis in their aligned direction. Collectively, this work presents a novel bioinspired redwood-like material with multifunctional properties that provides new insight into bone defect repair.

3D-plotted zinc silicate/β-tricalcium phosphate ceramic scaffolds enable fast osteogenesis by activating the p38 signaling pathway

“…Many studies documented that Si demonstrated tremendous angiogenic bioactivity. 31–34 Similarly, Zn was also found to possess an ability to introduce neovascularization. 35 Therefore, the Si and Zn ions sustainedly released from ZS/β-TCP scaffolds were contributive to the improvement in adhesion, viability, proliferation, osteogenic and angiogenic activities of mBMSCs and HUVECs.…”

Bioinspired Piezoelectric Periosteum to Augment Bone Regeneration via Synergistic Immunomodulation and Osteogenesis

“…BMSCs were isolated from femurs and tibiae marrow of SD rats according to an established protocol. 12 The isolated BMSCs were cultured with α-MEM supplemented with 10% FBS and 1% P/S in a humidified incubator at 37 °C with 5% CO 2 partial pressure. To identify the expression of cell surface markers of isolated cells, flow cytometric analysis was performed as previously described.…”

“…4,11 Although it is an appealing and highly efficacious growth factor-based treatment, the biological agents used to date can produce severe side effects (e.g., inflammation and immune response, excessive osteogenesis, and ectopic osteogenesis), impeding their further application. 12 Given the complexity of bone regeneration as well as the aforementioned dilemmas, these treatment modalities have experienced difficulties in clinical practical application with unknown adverse effects, biosecurity issues, and limited bioactivities (e.g., immunomodulation and osteogenesis), resulting in multiple complications in patients. 13 Likewise, the use of stem cells can cause harmful reactions and is limited by extensive in vitro cell manipulation, potential tumorigenesis, various ethical challenges, and difficulties in therapeutic translation and regulatory approval.…”

“…Furthermore, these bone-healing functions should be inextricably linked to the structure and components of the periosteum. , However, most artificial periosteum materials possess limited bioactivity for modulating immune responses and guiding endogenous cell recruitment and therefore produce unsatisfactory osteogenesis. For developing advanced periosteal biomaterials for augmented bone regeneration, extensive research has been devoted to integrating immunomodulatory molecules, such as interleukin (IL)-4, bone morphogenetic protein-2 (BMP-2), or vascular endothelial growth factor (VEGF), into artificial periosteum materials that can effectively modulate immune responses, vascularization, and bone marrow-derived mesenchymal stem cell (BMSC) recruitment. , Although it is an appealing and highly efficacious growth factor-based treatment, the biological agents used to date can produce severe side effects (e.g., inflammation and immune response, excessive osteogenesis, and ectopic osteogenesis), impeding their further application . Given the complexity of bone regeneration as well as the aforementioned dilemmas, these treatment modalities have experienced difficulties in clinical practical application with unknown adverse effects, biosecurity issues, and limited bioactivities (e.g., immunomodulation and osteogenesis), resulting in multiple complications in patients .…”

Freeze Casting with Bioceramics for Bone Graft Substitutes

“…While under vacuum, the material is percolated into the ceramic scaffold, either filling up the pores or coating the walls. Inversely of note, a slurry-based ceramic coating on a freeze-cast polymer scaffold with a ceramic composition of up to 45% was demonstrated by Wu et al [164].…”