Hierarchical Nanostructured Electrospun Membrane with Periosteum‐Mimic Microenvironment for Enhanced Bone Regeneration

Abstract

An ideal periosteum substitute should be able to mimic the periosteum microenvironment that continuously provides growth factors, recruits osteoblasts, and subsequent extracellular matrix (ECM) mineralization to accelerate bone regeneration. Here, a calcium‐binding peptide‐loaded poly(ε‐caprolactone) (PCL) electrospun membrane modified by the shish‐kebab structure that can mimic the periosteum microenvironment was developed as a bionic periosteum. The calcium‐binding peptide formed by the negatively charged heptaglutamate domain (E7) in the E7‐BMP‐2 with calcium ion in the tricalcium phosphate sol (TCP sol) through electrostatic chelation not only extended the release cycle of E7‐BMP‐2 but also promoted the biomineralization of the bionic periosteum. Cell experiments showed that the bionic periosteum could significantly improve the osteogenic differentiation of the rat‐bone marrow‐derived mesenchymal stem cells (rBMSCs) through both chemical composition and physical structure. The in vivo evaluation of the bionic periosteum confirmed the inherent osteogenesis of this periosteum microenvironment, which could promote the regeneration of vascularized bone tissue. Therefore, the hierarchical nanostructured electrospun membrane with periosteum‐mimic microenvironment is a promising periosteum substitute for the treatment of bone defects.

Electrospun nanofibers for bone regeneration: from biomimetic composition, structure to function

“…205 Another study also proved that the short chain BMP-2 peptide with a heptaglutamate domain (E7) obviously enhanced the conjugation efficiency to the HAp surface and averted the low half-life time as well as potential side effects of released BMP-2 proteins. 206 Apart from this, some more stable Chinese herbal components have been also loaded into nanofibers instead of growth factors to escort the bioactivity of the scaffold. For example, owing to the advantages of antibacterial and anti-inflammatory properties, inhibition of osteoclastic differentiation and promotion of osteogenic differentiation, 207 baicalin, a flavonoid glycoside, was incorporated into electrospun PCL/PLGA nanofibers.…”

Engineering Multifunctional Hydrogel With Osteogenic Capacity for Critical-Size Segmental Bone Defect Repair

“…The repair of critical-size segmental bone defects is still a great challenge in clinic. Over the past decades, different types of synthetic bone grafts have been developed, of which particularly calcium phosphate (CaP) and hydroxyapatite-based bone substitutes have shown great potential ( Zhao R. et al, 2020 ; Zhao Y. et al, 2020 ; Chae et al, 2021 ; Liu et al, 2021 ; He et al, 2022 ). In view of increased demands for synthetic bone grafts with advantageous properties, we designed a self-healing hydrogel consisting of PVA, Na 2 B 4 O 7 , and TEOS.…”

Periosteum-Inspired Membranes Integrated with Bioactive Magnesium Oxychloride Ceramic Nanoneedles for Guided Bone Regeneration

“…The extracellular matrix mineralization marks the late stage of osteogenesis. 15 We subsequently analyzed the calcium nodule formation using Alizarin Red S (ARS) assay after the 10-day incubation. ARS bound with the calcium nodules deposited on the membranes could be visualized (Figure 6C).…”

“…14 They are competitive alternatives to high-cost growth factors. 15,16 Mg-containing bioceramics have become increasingly popular bone-augmenting materials owing to their more appropriate dissolution rates and better bone-bonding ability than classic Ca-based ones. 17 More encouragingly, the released Mg ions (Mg 2+ ) play a vital role in bone metabolism, which can activate bone-tissue-specific cell responses and regulate immunological reactions.…”

“…GBR skips the induced membrane formation stage in the IMT technique, and a barrier membrane is directly applied to the osseous cavity to construct a pseudocapsule to prevent the rapidly growing non-osteogenic tissues from retarding bone regeneration. ,− More than a physical hindrance, this study devotes to endowing membranes with the desired bioactivity via integration of biofunctional agents to facilitate in-situ bone formation at a defect site. − Bioceramics have been continuously investigated in the bone-tissue-engineering field for their ability to elicit specific biological responses (e.g., osteogenesis and angiogenesis) during bone regeneration in vivo . ,, In particular, the bioactive ions delivered by degradable bioceramics, such as magnesium (Mg), calcium (Ca), silicon (Si), chlorine (Cl), and phosphate (PO 4 3– ), as well as the special surface nanotopography, effectively modulate stem cell functions to promote tissue remodeling . They are competitive alternatives to high-cost growth factors. , Mg-containing bioceramics have become increasingly popular bone-augmenting materials owing to their more appropriate dissolution rates and better bone-bonding ability than classic Ca-based ones . More encouragingly, the released Mg ions (Mg 2+ ) play a vital role in bone metabolism, which can activate bone-tissue-specific cell responses and regulate immunological reactions. − Hence, a membrane composited with Mg-based bioceramics that can create an inductive microenvironment for bone formation should have superior clinical impact, but such a material has been rarely reported. , …”