Abstract
Bone defects, massive bone defects in particular, is still an issue clinically. Acetylsalicylic acid (ASA), also known as aspirin, has been proven to be conducive for mesenchymal stem cells osteogenic differentiation, which may be benefited for bone regeneration. In order to achieve a more appealing prognosis of bone defect, here we develop a well-defined tetra-PEG hydrogel sealant with rapid gelation speed, strong tissue adhesion, and high mechanical strength. After in-situ encapsulation of aspirin, this drug-loaded tetra-PEG hydrogel possessed a sustained release, anti-inflammation, and osteoinductive properties. In vitro experiments showed that the cell proliferation was slightly facilitated, and the osteogenic differentiation was notably augmented when periodontal ligament stem cells (PDLSCs) were co-incubating with the hydrogel materials. Moreover, in vivo study manifested that the aspirin sustained release system significantly facilitated the PDLSCs mediated bone defect regeneration. Overall, tetra-PEG hydrogel-based aspirin sustained release system is applicable not only for enhancing the osteogenesis capacity of PDLSC but also providing a new thought of bone regenerative therapy.
Highlights
Autologous and allogenic bone grafts are currently the most common used therapeutic strategies for treating bone defect (Miller and Chiodo, 2016; Panagopoulos et al, 2017)
We investigated whether tetra-PEG hydrogels loaded with aspirin (PEG-Acetylsalicylic acid (ASA)) complex is a suitable scaffold for delivering aspirin locally, and we hypothesized that the PEG-ASA complex might serve as an ideal approach for periodontal ligament stem cells (PDLSCs)-mediated bone regeneration
In order to investigate the effect of ASA on osteogenic differentiation of PDLSCs and select an appropriate concentration to encapsulate ASA in the tetra-PEG hydrogel, we set up a series doses of ASA to treat PDLSCs and analyzed its osteogenic potential
Summary
Autologous and allogenic bone grafts are currently the most common used therapeutic strategies for treating bone defect (Miller and Chiodo, 2016; Panagopoulos et al, 2017). In comparison to currently available treatment modalities, mesenchymal stem cells (MSCs) based bone tissue engineering was indicated as an advantageous alternative therapeutic option for bone tissue regeneration (Botelho et al, 2017; Confalonieri et al, 2018), including high-quality regeneration capacity, low risk of autoimmune rejection, and no donor-site harvesting procedure. PEG-ASA Hydrogel for Bone Regeneration proliferation, immunomodulation, and multiple-lineage differentiation abilities when compared with bone marrow derived mesenchymal stem cells (BMMSCs) (Gronthos et al, 2000; Seo et al, 2004; Zhang et al, 2009). It was reported that ex vivo-expanded PDLSCs was capable of achieving better bone regeneration capacity compared with other types of dental derived MSCs (Moshaverinia et al, 2014), and they could be collected in dental clinic from discarded tissue samples. The data may provide a new therapeutic strategy for achieving anti-inflammation and bone regeneration in repairing cranial bone defects
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