Simple application of adipose-derived stem cell-derived extracellular vesicles coating enhances cytocompatibility and osteoinductivity of titanium implant

Abstract

Surface modification using bioactive molecules is frequently performed to improve the biological properties of medical metal biomaterial titanium (Ti) implants. Developmental evidence suggests that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) served as potent bioactive component. As a subset of MSC-EV, adipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) could be obtained from abundant adipose tissue. Meanwhile, it possesses multiple regenerative properties and might be used to endow biological activities to medical Ti implant. Here, we present a simple ADSC-EV coating strategy based on physisorption of fibronectin. This ADSC-EV functionalized Ti implants (EV-Ti) revealed enhanced osteoblast compatibility and osteoinductive activity. Cell spreading area of EV-Ti group was 1.62- and 1.48-fold larger than that of Ti group after 6 and 12 h of cell seeding, respectively. Moreover, EV-Ti promoted alkaline phosphatase, collagen 1 and osteocalcin gene expression in osteoblast by 1.51-, 1.68- and 1.82-fold compared with pristine Ti, respectively. Thus, the MSC-EVs modification method reported here provide a clinically translatable strategy to promote the bioactivity of Ti implants.

The advances in nanomedicine for bone and cartilage repair

“…Pansani et al immobilized EVs secreted by decidual mesenchymal stem cells (DEVs) on the implant surface, which not only promoted osteoblast proliferation, migration and deposition of mineral phases, but also directly stimulated the apposition of CaP on the Ti surface, thus improving HA formation and enhancing osseointegration of the implants [ 198 ]. Similarly, Chen et al proposed a coating strategy based on ADSC-derived EVs, and showed that the cell expansion area as well as ALP, collagen I and osteocalcin gene expression were significantly higher in the EV-Ti group than that of pure Ti, suggesting that functionalization of the surface using MSC-EVs could enhance the osteoinductive activity of the implants [ 199 ].…”

“…In addition to being used directly as biological agents for cartilage repair, or as bioactive coatings to functionalize the material surface for improved cell-implant interaction [ 198 , 199 ], exosomes can also be embedded in biomimetic scaffolds for their controlled release in cartilage tissue engineering. For instance, Hu et al demonstrated that human umbilical cord mesenchymal stem cells derived exosomes (hUC-MSCs-exosomes) containing GelMA/nanoclay hydrogel was effective in promoting cartilage regeneration.…”

Multifunctional Coatings of Titanium Implants Toward Promoting Osseointegration and Preventing Infection: Recent Developments

“…On the other hand, the membrane of EVs contains bioactive signaling molecules to obtain protection ( Malda et al, 2016 ; Tsiapalis and O’Driscoll, 2020 ). Based on physisorption of fibronectin, Chen et al immobilized adipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) onto the titanium surface, which enhanced osteoblast compatibility and osteoinduction activity ( Chen et al, 2020a ).…”

Application of osteoinductive calcium phosphate ceramics in giant cell tumor of the sacrum: report of six cases

“…Therefore, it is controversial how to manage the remaining cavity after extensive curettage. There are types of commonly used bone grafts including polymethylmethacrylate (PMMA) [ 7 ], autograft [ 8 ], allograft [ 9 ] and other artificial bone substitutes [ 10–12 ]. Because of direct weight-bearing and early radiographic detection of recurrence, PMMA was often used to fill the remaining cavity in the limb [ 13 , 14 ].…”

“…Also, the use of allograft is limited by immunological reaction rejection and fracture [ 14 , 17 , 18 ]. Other bone substitutes also have unique advantages but also inevitable disadvantages [ 10–12 ]. Therefore, the gold standard for remaining cavity management in sacral GCT has not yet been established [ 19 ].…”