A Bilayer Membrane Doped with Struvite Nanowires for Guided Bone Regeneration

Abstract

Guided bone regeneration (GBR) therapy demonstrates a prominent curative effect on the management of craniomaxillofacial (CMF) bone defects. In this study, a GBR membrane consisting of a microporous layer and a struvite‐nanowire‐doped fibrous layer is constructed via non‐solvent induced phase separation, followed by an electrospinning procedure to treat critical‐sized calvarial defects. The microporous layer shows selective permeability for excluding the rapid‐growing non‐osteogenic tissues and potential wound stabilization. The nanowire‐like struvite is synthesized as the deliverable therapeutic agent within the fibrous layer to facilitate bone regeneration. Such a membrane displays a well‐developed heterogeneous architecture, satisfactory mechanical performance, and long‐lasting characteristics. The in vitro biological evaluation reveals that apart from being a strong barrier, the bilayer struvite‐laden membrane can actively promote cellular adhesion, proliferation, and osteogenic differentiation. Consequently, the multifunctional struvite‐doped membranes are applied to treat 5 mm‐sized bilateral calvarial defects in rats, resulting in overall improved healing outcomes compared with the untreated or the struvite‐free membrane‐treated group, which is characterized by enhanced osteogenesis and significantly increased new bone formation. The encouraging preclinical results reveal the great potential of the bilayer struvite‐doped membrane as a clinical GBR device for augmenting large‐area CMF bone reconstruction.

Multiphasic Membranes/Scaffolds for Periodontal Guided Tissue Regeneration

“…[30] Considering that alveolar bone loss can often occur in the context of periodontitis or tooth-replacement procedure, many studies have devoted to regenerating the defective bony tissues (Table 1). [15,[31][32][33][34][35] To endow the membrane with additional osteo-promotive properties, therapeutic additives would further be incorporated, like bioceramics (e.g., magnesium-containing bioceramics, hydroxyapatite and calcium phosphate) or growth factors (e.g., bone morphogenic proteins). Recently, our group has reported an asymmetric periosteum-mimicking guided bone regeneration (GBR) membrane through a two-step electrospinning procedure, whereby the blend of polycaprolactone (PCL) and gelatin A (GelA) was the membrane matrix and the magnesium oxychloride ceramic (MOC) nanoneedle was the deliverable osteoinductive factor.…”

“…Later, a dual-phase GBR membrane consisting of a selectivepermeable microporous layer and an osteoconductive struvitenanowire-laden fibrous layer was constructed using our previously developed non-solvent induced phase separation (NIPS) technique followed by electrospinning, [36][37][38] which showed superior healing performance in the repair of the critical-sized rat calvarial defects (Figure 2C). [34] 3D printing has been popular in tissue engineering field, for the feasibility to construct 3D porous scaffolds with pre-tailorized and personalized architectures. [39,40] Hence, the combination of 3D printing with the electrospinning technique turns out to be a promising strategy to establish a bilayer scaffold for GTR/GBR applications.…”

“…In vitro, -The microporous layer showed effective exclusion for fibroblasts -The fibrous PCL/struvite layer showed superior osteoconductivity In vivo, -5 mm-sized bilateral calvarial defect model in rats -The struvite-doped bilayer membrane could significantly enhance the in situ osteogenesis and bony regeneration, as well as the wound stabilization [34] - formed cementum and alveolar bone was observed, which can be attributed by the recruitment of host MSCs and the activation of the transforming growth factor beta 1/Smad3 signaling pathway, exhibiting the great potential for reconstructing the native periodontium.…”

“…C) A bilayer GBR membrane consisting of a selective-permeable microporous layer and an osteoinductive struvite-nanowire-laden fibrous layer is fabricated through the combination of non-solvent induced phase separation (NIPS) and electrospinning techniques, which displays prominent regenerative efficacy in the repair of critical-sized rat calvarial defects. Reproduced with permission [34]. Copyright 2022, Wiley-VCH GmbH.…”

Electrospun Biomimetic Periosteum Capable of Controlled Release of Multiple Agents for Programmed Promoting Bone Regeneration

“…Additionally, bone defect repair requires protection against adverse external tissue effects and an internal microenvironment to regulate osteogenesis. [31] Electrospinning bilayer membranes with an asymmetric structure are expected to construct a biomimetic periosteum to repair bone defects. The main advantage of asymmetric structures is that each surface's morphological structure, composition, and bioactivity are individually adjusted to optimize the overall performance of the membrane.…”