Resveratrol and Celastrol Loaded Collagen Dental Implants Regulate Periodontal Ligament Fibroblast Growth and Osteoclastogenesis of Bone Marrow Macrophages

Abstract

Collagen is widely used for dental therapy in several ways such as films, 3D matrix, and composites, besides traditional Chinese medicine (TCM), has been used in tissue regeneration and wound healing application for centuries. Hence, the present study was targeted for the first time to fabricate collagen film with TCM such as resveratrol and celastrol in order to investigate the human periodontal ligament fibroblasts (HPLF) growth and bone marrow macrophages (BMM) derived osteoclastogenesis. Further, the physicochemical, mechanical and biological activities of collagen‐TCM films crosslinked by glycerol and EDC‐NHS (1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide‐N‐hydroxysulfosuccinimide) were investigated. Collagen film characterization was significantly regulated by the nature of plasticizers like hydrophobic and degree of polarity. Interestingly, the collagen film's denaturation temperature was increased by EDC‐NHS than glycerol. FT‐IR data confirmed the functional group changes due to chemical interaction of collagen with TCM. Morphological changes of HPLF cells cultured in control and collagen films were observed by SEM. Importantly, the addition of resveratrol upregulated the proliferation of HPLF cells, while osteoclastogenesis of BMM cells treated with mCSF‐RANKL was significantly downregulated by celastrol. Accordingly, the collagen‐TCM film could be an interesting material for dental regeneration, and especially it is a therapeutic target to restrain the elevated bone resorption during osteoporosis.

Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo

“…Our results demonstrated that celastrol significantly inhibited mature osteoclast function via the bone resorption pit assay. In line with our results, Wang's research also found that celastrol had an inhibitory effect on osteoclast differentiation (Wang et al, 2020). Additionally, we also observed reduced F-actin formation in mature osteoclasts that was associated with impaired bone resorption activity following celastrol treatment.…”

Precision-engineered niche for directed differentiation of MSCs to lineage-restricted mineralized tissues

“…Broadly, these design features emphasize the precise configurations for the soluble (biomolecules) and insoluble (material topology) cues within these biomaterial systems for functional tissues and organ systems. 52 – 54 We recently demonstrated the ability of photoactivated latent TGF-β1 directs differentiation of dental stem cells to generate osteodentin. 23 The significance of regenerative dentistry aims to retain the structure and strength of the tooth while preserving pulp vitality.…”

Trans-Resveratrol: From Phytonutrient Supplement, to Novel Nanotherapeutic Agent

“…(CEL), and loaded into a collagen film to enhance the effectiveness of coated dental implants by Wang et al [55]. Using SEM and histochemistry, it was determined that the RES-loaded collagen films stimulated the most proliferation of the human periodontal ligamental fibroblasts (HPLFs), whilst the CEL-loaded films, demonstrated the lowest bone marrow macrophage-mediated osteogenesis.…”

“…Using SEM and histochemistry, it was determined that the RES-loaded collagen films stimulated the most proliferation of the human periodontal ligamental fibroblasts (HPLFs), whilst the CEL-loaded films, demonstrated the lowest bone marrow macrophage-mediated osteogenesis. Hence, it was suggested that using both RES and CEL in the collagen film was a promising approach to the development of an efficacious dental regenerative agent [55].…”