Effect of a Single Injection of Benidipine-Impregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket

Abstract

Objective: A dihydropyridine-type calcium channel blocker, benidipine (BD), is extensively used in hypertension therapy. In vitro study reported BD promoting bone metabolism. We evaluated the effect of sustained release of BDloaded poly(lactic-co-glycolic acid) (PLGA) microcarriers on the promotion of bone and gingival healing at an extraction socket in vivo. In addition, the effect of BD on osteoblasts, osteocytes, fibroblasts, and epithelial cells was evaluated in vitro. Approach: The maxillary first molar of rats was extracted. Next, PLGA microcarriers containing BD were directly injected into the gingivobuccal fold as a single dose. After injection, bone and soft-tissue healing was histologically evaluated. Effect of BD on proliferation, migration, and gene expression of gingival and bone cell was also examined in vitro. Results: After tooth extraction, BD significantly augmented bone volume and density, and also epithelial wound healing. During in vitro studies, BD promoted significant proliferation and migration of fibroblasts and epithelial cells. Real-time RT-PCR revealed that BD upregulated messenger RNA expression of Ahsg (alpha 2-HS glycoprotein) and Csf2 (colony-stimulating factor 2) in osteoblasts. Innovation: The prevention of bone and soft-tissue reduction associated with tooth extraction has been eagerly anticipated in the field of dentistry. This study first reported the effect of BD on extraction socket healing. Conclusion: A single dose of topically administered BD-loaded PLGA microcarriers promoted bone and soft-tissue healing at the extraction site of tooth.

Anti‐Swelling, Robust, and Adhesive Extracellular Matrix‐Mimicking Hydrogel Used as Intraoral Dressing

“…Due to its softness and high‐water content, hydrogel is a popular material for wound dressings. In dentistry, hydrogels, such as chitosan‐poly(γ‐glutamic acid), [ 4 ] collagen, [ 5 ] poly(lactic‐co‐glycolic acid), [ 6 ] and polyethyleneimine‐poly(vinyl pyrrolidone) [ 7 ] hydrogels, are commonly used as fillers for extraction wounds. However, most of these hydrogels fail to resist loading and to provide reliable barrier protection for wounds against mechanical disturbances generated by physiological actions in the oral environment, such as chewing, swallowing, or sneezing.…”

“…[3] Therefore, it is imperative to develop an intraoral wound healing-specific dressing to provide durable and robust isolation from the wet, dynamic environment of the oral cavity.Due to its softness and high-water content, hydrogel is a popular material for wound dressings. In dentistry, hydrogels, such as chitosan-poly(γ-glutamic acid), [4] collagen, [5] poly(lactic-coglycolic acid), [6] and polyethyleneimine-poly(vinyl pyrrolidone) [7] Due to the wet and dynamic environment of the oral cavity, the healing of intraoral wounds, such as tooth extraction wounds, requires stable and firm wound dressings. In clinical practice, cotton balls and gauzes, sponge plugs, or sutures are used to treat extraction wounds, but none of these means can continuously isolate the wound from the intraoral environment and facilitate ideal healing conditions.…”

Therapeutic Effect of Benidipine on Medication-Related Osteonecrosis of the Jaw

“…In addition, some culturing studies indicate that BD can enhance bone formation [17][18][19][20]. Our previous report also indicated that BD can accelerate bone healing in tooth extraction sockets [16]. These studies evoke the possibility that BD has modulatory functions on bone formation, which may also play a crucial role in the onset and/or healing of MRONJ.…”

“…A hypothesis can be created in that accelerated gingival wound healing may reduce the chance of bone exposure in the oral cavity and subsequent bone infection. In our recent report, benidipine (BD), a calcium channel blocker that has been used as an antihypertensive and antiarrhythmic agent [13][14][15], was found to promote the healing of gingival soft tissue around tooth extraction sockets [16]; thus, we hypothesized that BD is a possible candidate for a curative remedy. In addition, some culturing studies indicate that BD can enhance bone formation [17][18][19][20].…”

Replacement Process of Carbonate Apatite by Alveolar Bone in a Rat Extraction Socket

“…The experimental schedule is shown in Figure 2A. The right maxillary first (M1) and second molars (M2) were extracted under a combination anesthetic (0.3 mg/kg of medetomidine, 4.0 mg/kg of midazolam, and 5.0 mg/kg of butorphanol) [ 20 ]. After extraction, the alveoli were filled with AB, CO 3 Ap, or without filling and the animals were randomly selected into three groups (control, AB, and CO 3 Ap).…”