Spatiotemporal Management of the Osteoimmunomodulation of Fibrous Scaffolds by Loading a Novel Amphiphilic Nanomedicine

Abstract

Implanted bone scaffolds or their biodegradation products may disturb the sequential functions of distinct macrophage phenotypes and cause improper timing of macrophage activation, resulting in delayed or dysfunctional bone regeneration. Although spatiotemporal manipulation of the immune response has been recognized as a promising strategy to address this issue, developing satisfactory drug delivery systems with the function of proper timing control on the macrophage phenotype transformation from pro-inflammatory M1 to anti-inflammatory M2 phenotype still remains a challenge. Here, we propose an amphiphilic nanomedicine with dual anti-inflammatory functions and inflammation-responsive drug release properties to spatiotemporally manage the osteoimmunomodulation of the bone scaffold. The nanomedicine enables the modified scaffold to manipulate the immune response in a staged manner, not only avoiding the overinhibition of M1 macrophages in the initial phase but also facilitating its polarization to M2 phenotype, as well as exhibiting full-course inhibition on later biodegradation-induced inflammation. The described immunomodulatory manner attempts to conform to the principle of osteoimmunomodulation, consequently resulting in better in vivo osteogenesis compared with traditional drug delivery systems. We anticipate that this strategy might aid the development of advanced immunomodulatory bone biomaterials.

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

“…72 In their latest-reported study, they constructed a nanofibrous scaffold to realize spatiotemporal management for osteoimmunomodulation, by loading a novel amphiphilic nanomedicine with dual anti-inflammatory function and inflammation-responsive drug release properties. 238 In the early stage, the nanomedicine enriched on the surface of nanofibers could scavenge the surrounding reactive oxygen species and maintain the acute inflammation at a moderate level, thus promoting the transformation of the macrophage from M1 to M2 phenotype. At a later stage, the accelerated degradation of the scaffold would allow more embedded nanomedicine to be exposed to the inflammatory environment, thus bringing about the inflammation-responsive release profile for bone tissue regeneration.…”

“…At a later stage, the accelerated degradation of the scaffold would allow more embedded nanomedicine to be exposed to the inflammatory environment, thus bringing about the inflammation-responsive release profile for bone tissue regeneration. 238…”

A Straightforward Approach towards Antibacterial and Anti‐Inflammatory Multifunctional Nanofiber Membranes with Sustained Drug Release Profiles

“…are widely applied in wound dressings. [20][21][22][23] Notably, indomethacin (Indo), which exerts its anti-inflammatory effect by inhibiting the production of prostaglandins (PGs), is an NSAID with very effective antipyretic, analgesic, and antiinflammatory activity, and fewer side effects and higher safety compared with corticosteroids. [24,25] In order to enhance the anti-inflammatory ability of wound dressings, Indo is often selected to be incorporated in situ into nanofiber membranes, such as polyvinylpyrrolidone-Indo nanofiber membrane (Rasekh et al) [26] and corn protein zein-hydrophobic ethyl cellulose-Indo composite nanofiber membrane (Lu et al).…”

Metal–phenolic networks acted as a novel bio-filler of a barrier membrane to improve guided bone regenerationviamanipulating osteoimmunomodulation

“…8 Therefore, more attention should be paid to achieve favourable osteoimmunomodulation of polyester based barrier membranes for the development of next generation barrier products. 9…”

“…8 Therefore, more attention should be paid to achieve favourable osteoimmunomodulation of polyester based barrier membranes for the development of next generation barrier products. 9 Incorporating nutrient elements, such as Ca, Mg, Zn, or Sr, has been demonstrated as a valuable strategy to manipulate osteoimmunomodulation of bone biomaterials. For instance, Zhang et al incorporated a layer of Zn into PEEK biomaterials to enhance osteointegration between the Zn-coated PEEK and bone tissue by modulating nonactivated macrophage polarization to an anti-inflammatory phenotype and to induce the secretion of anti-inflammatory cytokines.…”