The spatial form periosteal-bone complex promotes bone regeneration by coordinating macrophage polarization and osteogenic-angiogenic events

Abstract

Bone defects associated with soft tissue injuries are an important cause of deformity that threatens people’s health and quality of life. Although bone substitutes have been extensively explored, effective biomaterials that can coordinate early inflammation regulation and subsequent repair events are still lacking. We prepared a spatial form periosteal bone extracellular matrix (ECM) scaffold, which has advantages in terms of low immunogenicity, good retention of bioactive ingredients, and a natural spatial structure. The periosteal bone ECM scaffold with the relatively low-stiffness periosteum (41.6 ± 3.7 kPa) could inhibit iNOS and IL-1β expression, which might be related to actin-mediated YAP translocation. It also helped to promote CD206 expression with the potential influence of proteins related to immune regulation. Moreover, the scaffold combined the excellent properties of decalcified bone and periosteum, promoted the formation of blood vessels, and good osteogenic differentiation (RUNX2, Col 1α1, ALP, OPN, and OCN), and achieved good repair of a cranial defect in rats. This scaffold, with its natural structural and biological advantages, provides a new idea for bone healing treatment that is aligned with bone physiology.

Strategies for Enhancing Vascularization of Biomaterial‐Based Scaffold in Bone Regeneration

“…[79] Immunocompatible scaffold derived from periosteal ECM also promoted timely polarization with coordinated angiogenic events [Figure 1]. [80] Interestingly, employing microporous silicified scaffold with collagen into intrafibrillar spaces, caused the release of silicic acid responsible for monocytic production of cytokines that stimulates the vascular quality, in vivo. [81]…”

“…3D printed biodegradable scaffolds participate in the clinical formation of new mineral callus, allowing the perfusion of bodily fluids into interconnecting channels, later occupied by active cells to form endothelium and blood vessels with the production of the normal bone matrix as the scaffold is replaced. [92] Thus, various scaffolds microfabricated, require an evaluation of structural modifications like porosity, pore interconnectivity, pore size, biocompatibility with cellular and [80] biomolecule components, surface topography, and mechanical strength. [93] These architectural precisions may be manifested identically after producing a virtual biomimetic bone scaffold model using computer designing software like the Voronoi tessellation method.…”

“…The spatial form periosteal bone scaffold achieved good bone healing. (A) micro-CT 4 and 8 weeks after implantation [Reproduced with permission from Elsevier, 2021] [80].…”

In Situ Biomimetic Mineralization of Bone-Like Hydroxyapatite in Hydrogel for the Acceleration of Bone Regeneration

“…The unique configurations, tunable physicochemical properties, and excellent biocompatibility of hydrogels significantly promote bone regeneration . Moreover, some naturally derived materials, such as a decellularized extracellular matrix (ECM), exhibits superior behavior in bone regrowth owing to the direct duplication of osteogenic-related biomolecules. − The mimetic nature of inorganic components is another important issue for bone regeneration. Nano-HAP promotes osteogenesis by increasing the expression of bone markers, such as osteopontin, osteocalcin, and alkaline phosphatase (ALP) .…”

Spatiotemporal Regulation of the Bone Immune Microenvironment via Dam‐Like Biphasic Bionic Periosteum for Bone Regeneration

“…[ 15 ] Hydrogels derived from the periosteal matrix can promote angiogenesis and bone regeneration through immune regulation. [ 16 ] Composites of electrospun fiber membranes and hydrogels inherit the high mechanical strength and strong barrier effect of the natural periosteum as well as the good biocompatibility of the hydrogel. [ 17 ] Thus, we postulated that a dense hydrogel coating can be constructed and attached to the surface of micro‐sol electrospun fibers as the gel phase to capture and store IL‐4 in the early stage, thus achieving spatiotemporal regulation of the immune response.…”