Aptamers recognizing fibronectin confer improved bioactivity to biomaterials and promote new bone formation in a periodontal defect in rats

Abstract

The use of alloplastic materials in periodontal regenerative therapies is limited by their incapacity to establish a dynamic dialog with the surrounding milieu. The aim of the present study was to control biomaterial surface bioactivity by introducing aptamers to induce the selective adsorption of fibronectin from blood, thus promoting platelets activation in vitro and bone regeneration in vivo. A hyaluronic acid/polyethyleneglycole-based hydrogel was enriched with aptamers selected for recognizing and binding fibronectin. In vitro, the capacity of constructs to support osteoblast adhesion, as well as platelets aggregation and activation was assessed by chemiluminescence within 24 h. Matrices were then evaluated in a rat periodontal defect to assess their regenerative potential by microcomputed tomography (µCT) and their osteogenic capacity by Luminex assay 5, 15 and 30 d postoperatively. Aptamers were found to confer matrices the capacity of sustaining firm cell adhesion (p = 0.0377) and to promote platelets activation (p = 0.0442). In vivo, aptamers promoted new bone formation 30 d post-operatively (p < 0.001) by enhancing osteoblastic lineage commitment maturation. Aptamers are a viable surface modification, which confers alloplastic materials the potential capacity to orchestrate blood clot formation, thus controlling bone healing.

Aptamer-enriched scaffolds for tissue regeneration: a systematic review of the literature

“…Of the 48 eligible articles, 30 more were excluded after full-text assessment. 18 articles were included in the final analysis: Nine articles were related to only in vitro biological testing ( Guo et al, 2005 ; Hoffmann et al, 2008 ; Chen et al, 2012 ; Galli et al, 2016 ; Zhang et al, 2016 ; Parisi et al, 2017b ; Wang et al, 2019a ; Parisi et al, 2019 ; Zhao et al, 2019 ), 1 to only in vivo testing ( Enam et al, 2017 ) and eight presented results of in vitro and in vivo testing of aptamer-grafted biomaterials ( Wang et al, 2017 ; Zhao et al, 2017 ; Wang et al, 2019b ; Kuang et al, 2019 ; Kim et al, 2021 ; Parisi et al, 2021 ; Sun et al, 2021 ; Zhao et al, 2021 ). Records identification, screening, eligibility, and inclusion is presented in Figure 2 .…”

“…We identified them as Strategy A, B and C ( Figure 3 ). Strategy A was adopted by four studies ( Galli et al, 2016 ; Parisi et al, 2017b ; Parisi et al, 2019 ; Parisi et al, 2021 ) and concerns the selection of aptamers selected against adhesive macromolecules. After implantation, biomaterials are immediately soaked with patient’s own biological fluid (e.g., blood) and conditioned with proteins contained in it.…”

“…To assess proper colonization of the scaffold nine records investigated cell adhesion ( Guo et al, 2005 ; Hoffmann et al, 2008 ; Chen et al, 2012 ; Zhang et al, 2016 ; Parisi et al, 2017b ; Wang et al, 2019a ; Parisi et al, 2019 ; Kim et al, 2021 ; Parisi et al, 2021 ) and found out a significative increased number of adhered cells in the aptamer groups. Time frame for cell adhesion observations ranged from 4 to 24 h. When aptamers selected against specific cells were used, selective adhesion of the target cell could be investigated ( Chen et al, 2012 ; Wang et al, 2019a ; Wang et al, 2019b ; Kim et al, 2021 ).…”

“…Yet, the use of aptamers promoted cell migration in all the records considered. To further support the role of aptamers in promoting biomaterial colonization, next to adhesion and/or migration, 10 studies also investigated cell viability or proliferation, ( Galli et al, 2016 ; Zhang et al, 2016 ; Parisi et al, 2017b ; Zhao et al, 2017 ; Wang et al, 2019a ; Zhao et al, 2019 ; Kim et al, 2021 ; Parisi et al, 2021 ; Sun et al, 2021 ; Zhao et al, 2021 ). Methods to detect cell viability included stainings (i.e., Calcein-AM or Trypan Blue exclusion assay) and quantification of cell metabolic activity and viability by tetrazolium salts or chemiluminescence assays, respectively.…”

“…Still a relative limited number of records used pre-clinical models to investigate whether aptamers are a good modification to support regeneration in diverse tissues ( Table 2 ). The target tissue considered in the literature were bone (four studies) ( Wang et al, 2017 ; Kuang et al, 2019 ; Parisi et al, 2021 ; Sun et al, 2021 ), cartilage (one study) ( Wang et al, 2019b ), vascular tissue (two studies) ( Zhao et al, 2019 ; Zhao et al, 2021 ), liver (one study) ( Kim et al, 2017 ) and skin (one study) ( Enam et al, 2017 ).…”