Hyaluronic  acid  as  an  active  agent  to  accelerate  bone   regeneration aftertooth extraction: a literature review

Tooth extraction is a dental treatment that is performed frequently in dentistry. This procedure will stimulate a sophisticated healing process involving a variety of biological factors although it takes a long time to complete. Three phases occur in this process i.e. the inflammatory phase, the proliferation phase, and the remodeling phase which aim to restore the tissue function. Several interventions can be used to accelerate bone formation after tooth extraction. Recently, hyaluronic acid (HA) has been commonly used in dentistry due to their essential physiological effects for the periodontal connective tissue, gingiva, and alveolar bone. Hyaluronic acidis a natural non-sulfate glycosaminoglycans compound that has high molecular weight consisting of D-glucuronic acid and N-acetylglucosamine. Hyaluronic acidis also a component of the extracellular matrix that plays an important role in morphogenesis and tissue healing. The mechanism of action of HA works in two ways, that is passive and active mechanism. The passive mechanism is depend on physical and chemical properties of HA that can change the molecular weight and concentration properties. The active mechanism of HA works by stimulating signal transduction pathway initiated by ligand binding with its receptors through autocrine or paracrine processes. The administration of HA can accelerate bone formation due to it can enhance bone morphogenetic protein (BMP) which belongs to the TGF- β superfamily that has high osteogenic capacity. The HA works through a passive mechanism that depends on its molecular weight and an active mechanism by increasing BMP activity.

Download Full-text

Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure

Pharmaceuticals ◽

10.3390/ph14040301 ◽

2021 ◽

Vol 14 (4) ◽

pp. 301

Author(s):

Yayoi Kawano ◽

Viorica Patrulea ◽

Emmanuelle Sublet ◽

Gerrit Borchard ◽

Takuya Iyoda ◽

...

Keyword(s):

Gene Expression ◽

Molecular Weight ◽

Wound Healing ◽

Hyaluronic Acid ◽

Healing Process ◽

Dermal Fibroblasts ◽

Water Soluble ◽

Wound Healing Process ◽

And Migration ◽

Proliferation And Migration

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.

Download Full-text

Influence of Homemade and Commercial Fibrin Sealant on Alveolar Bone Healing - an Experimental Study.

Blood ◽

10.1182/blood.v104.11.4110.4110 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4110-4110

Author(s):

Maria Elvira P. Correa ◽

Oslei P. Almeida ◽

Danyel Peres ◽

Marcelo C. Alves ◽

Fernando F. Costa ◽

...

Keyword(s):

Bone Formation ◽

Bone Healing ◽

Fibrin Sealant ◽

Factor Xiii ◽

Alveolar Bone ◽

Healing Process ◽

Control Group ◽

Image Analysis System ◽

New Bone Formation ◽

Fibrin Sealants

Abstract The beneficial aspects of fibrin sealants for soft tissues are well documented, but studies of their direct influence on bone healing and their effectiveness in augmenting bone graft healing have produced conflicting results. The aim of this study was to evaluate the influence of fibrin sealants (FS) in the alveolar bone healing process during a period of up to 28 days. Seventy-five Wistar rats were submitted to a superior incisor extraction after intramuscular anesthesia (kentamine chloridrate 10% – 10mg/kg and tiazina chloridrate-5mg/kg). The rats were divided into tree different groups and the sealants were introduced into the alveolar bone. The first group (25) received human homemade fibrin glue, the second group (25) FS associated to factor XIII and aprotinin (Beriplast; Aventis-Beringher) and the third group (25) was the control. Animals were sacrificed by prolonged diethyl inhalation on days 7, 14 and 28 after surgery. Animal craniums were dissected and submitted to a decalcification, and preparated for H&E light microscopy. The morphometric study was performed by means of an interactive computerized image analysis system KS400 (Zeiss, Jena). New bone formation was carefully delimited in four different alveolar regions (apical, two middle areas and cervical) of each specimen. The data were statistically analyzed using multiple regression, ANOVA and Tukey test. Results showed that the amount of alveolar bone formation (μm) in the control group and commercial sealant was statistically similar. However, alveolus receiving homemade sealant presented less amount of new bone formation comparing to commercial sealant and control group (p=0.0034) (figure 1). The present study demonstrated that homemade fibrin sealant delays osteogenic formation. Commercial sealant did not improve alveolar repair however, the amount of new bone formation was slightly higher comparing to the control, probably due to the factor XIII present in this sealant. Figure Figure

Download Full-text

The effect of a combination of propolis extract and bovine bone graft on the quantity of fibroblasts, osteoblasts and osteoclasts in tooth extraction sockets

Dental Journal (Majalah Kedokteran Gigi) ◽

10.20473/j.djmkg.v52.i3.p126-132 ◽

2019 ◽

Vol 52 (3) ◽

pp. 126

Author(s):

Louisa Christy Lunardhi ◽

Utari Kresnoadi ◽

Bambang Agustono

Keyword(s):

Statistical Analysis ◽

Bone Graft ◽

Active Substance ◽

Tooth Extraction ◽

Alveolar Bone ◽

Healing Process ◽

Bovine Bone ◽

Propolis Extract ◽

Significant Difference ◽

Average Quantity

Background: Tooth extraction is a procedure frequently performed in the field of dentistry that can cause alveolar bone resorption during the healing process. Therefore, preservation of sockets is necessary to maintain alveolar bone which represents one of the important factors in the successful manufacture of dentures. A combination of propolis extract and bovine bone graft (BBG) can accelerate bone regeneration. Purpose: The purpose of this study was to determine the effects of a combination of propolis extract and BBG on the quantity of fibroblasts, osteoblasts, and osteoclasts in the tooth extraction socket. Methods: 56 Cavia cobaya were divided into eight groups. The lower left incisor of each subject was extracted and induced with polyethylene glycol (PEG), propolis extract + PEG, BBG + PEG, combination of propolis extract + BBG + PEG at a concentration of 2% active substance. Experimental subjects were sacrificed on days 3 and 7. Histopathological examination with a microscope at 400x magnification was conducted to calculate the quantity of fibroblasts, osteoblasts, and osteoclasts. Statistical analysis was performed by one-way ANOVA and Tukey HSD tests. Results: The highest average quantity of fibroblasts and osteoblasts and the lowest average quantity of osteoclasts occurred in the group to which a combination of propolis extract and BBG had been administered on both days 3 and 7. According to the statistical analysis results, all the treatment groups recorded a significant difference in the quantity of fibroblasts, osteoblasts, and osteoclasts with a p value: 0.000 (p<0.05). Conclusion: A combination of propolis extract and BBG can increase the quantity of fibroblast and osteoblast cells, while reducing the number of osteoclast cells in tooth extraction sockets treated with 2% concentration of the active substance.

Download Full-text

Carbonate Apatite Containing Statin Enhances Bone Formation in Healing Incisal Extraction Sockets in Rats

Materials ◽

10.3390/ma11071201 ◽

2018 ◽

Vol 11 (7) ◽

pp. 1201 ◽

Cited By ~ 3

Author(s):

Yunia Rakhmatia ◽

Yasunori Ayukawa ◽

Akihiro Furuhashi ◽

Kiyoshi Koyano

Keyword(s):

Bone Formation ◽

Tooth Extraction ◽

Alveolar Bone ◽

Vertical Plane ◽

Precipitation Reaction ◽

Carbonate Apatite ◽

Mixed Solution ◽

Micro Computed Tomography ◽

Mineral Density ◽

Trabecular Thickness

The purpose of this study was to evaluate the feasibility of using apatite blocks fabricated by a dissolution–precipitation reaction of preset gypsum, with or without statin, to enhance bone formation during socket healing after tooth extraction. Preset gypsum blocks were immersed in a Na3PO4 aqueous solution to make hydroxyapatite (HA) low crystalline and HA containing statin (HAFS), or in a mixed solution of Na2HPO4 and NaHCO3 to make carbonate apatite (CO) and CO containing statin (COFS). The right mandibular incisors of four-week-old male Wistar rats were extracted and the sockets were filled with one of the bone substitutes or left untreated as a control (C). The animals were sacrificed at two and four weeks. Areas in the healing socket were evaluated by micro-computed tomography (micro-CT) and histological analyses. The bone volume, trabecular thickness, and trabecular separation were greatest in the COFS group, followed by the CO, HAFS, HA, and C groups. The bone mineral density of the COFS group was greater than that of the other groups when evaluated in the vertical plane. The results of this study suggest that COFS not only allowed, but also promoted, bone healing in the socket. This finding could be applicable for alveolar bone preservation after tooth extraction.

Download Full-text

The Effect of a combination of 12% spirulina and 20% chitosan on macrophage, PMN, and lymphocyte cell expressions in post extraction wound

Dental Journal (Majalah Kedokteran Gigi) ◽

10.20473/j.djmkg.v50.i2.p106-110 ◽

2017 ◽

Vol 50 (2) ◽

pp. 106

Author(s):

Nike Hendrijantini ◽

Rostiny Rostiny ◽

Mefina Kuntjoro ◽

Kevin Young ◽

Bunga Shafira ◽

...

Keyword(s):

Statistical Analysis ◽

Animal Models ◽

Tooth Extraction ◽

Acute Inflammation ◽

Alveolar Bone ◽

Healing Process ◽

Control Group ◽

Test Results ◽

Group Members ◽

Lymphocyte Cell

Background: Tooth extraction is the ultimate treatment option for defective teeth followed by the need for dentures. Inflammation is one phase of the healing process that should be minimized in order to preserve alveolar bone for denture support. Macrophage, PMN and lymphocyte cells are indicators of acute inflammation. Spirulina and chitosan are natural compounds with the potential to be anti-inflammatory agents. Purpose: This research aimed to determine macrophage, PMN and lymphocyte cells of animal models treated with a combination of 12% spirulina and 20% chitosan on the 1st, 2nd and 3rd post-extraction day. Methods: Animal models were randomly divided into control (K) and treatment (P) groups. Each group was further divided into three subgroups (KI, KII, KIII and PI, PII, PIII). The post-extraction sockets of the control group animals were then filled with CMC Na 3%. Meanwhile, the post-extraction sockets of the treatment group members were filled with a combination of 12% spirulina and 20% chitosan. Subsequently, the number of PMN, macrophage and lymphocyte cells was analyzed by means of HE analysis on the 1st., 2nd. and 3rd. days. Statistical analysis was then performed using a T-test. Results: There was a decrease in PMN cells and an increase in macrophage and lymphocyte cells on Days 1, 2, and 3. Conclusion: It can be concluded that a combination of 12% spirulina and 20% chitosan can not only decrease PMN cells, but can also increase macrophage and lymphocyte cells on Days 1, 2 and 3 after tooth extraction.

Download Full-text

Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model

European Journal of Pharmacology ◽

10.1016/j.ejphar.2016.04.049 ◽

2016 ◽

Vol 782 ◽

pp. 89-97 ◽

Cited By ~ 7

Author(s):

Yuki Arai ◽

Kazuhiro Aoki ◽

Yasuhiro Shimizu ◽

Yasuhiko Tabata ◽

Takashi Ono ◽

...

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Tooth Extraction ◽

Alveolar Bone ◽

De Novo ◽

Alveolar Bone Loss ◽

Extraction Model

Download Full-text

A Low Molecular Weight Hyaluronic Acid Derivative Accelerates Excisional Wound Healing by Modulating Pro-Inflammation, Promoting Epithelialization and Neovascularization, and Remodeling Collagen

International Journal of Molecular Sciences ◽

10.3390/ijms20153722 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3722 ◽

Cited By ~ 9

Author(s):

Yin Gao ◽

Yao Sun ◽

Hao Yang ◽

Pengyu Qiu ◽

Zhongcheng Cong ◽

...

Keyword(s):

Molecular Weight ◽

Wound Healing ◽

Hyaluronic Acid ◽

Molecular Mechanisms ◽

Healing Process ◽

Low Molecular Weight ◽

Cutaneous Wound Healing ◽

Cutaneous Wound

Recent knowledge of the cellular and molecular mechanisms underlying cutaneous wound healing has advanced the development of medical products. However, patients still suffer from the failure of current treatments, due to the complexity of healing process and thus novel therapeutic approaches are urgently needed. Previously, our laboratories produced a range of low molecular weight hyaluronic acid (LMW-HA) fragments, where a proportion of the glucosamine moieties were chemically N-acyl substituted. Specifically, N-butyrylation results in anti-inflammatory properties in a macrophage system, and we demonstrate the importance of N-acyl substituents in modulating the inflammatory response of LMW-HA. We have set up an inter-institutional collaborative program to examine the biomedical applications of the N-butyrylated LMW-HA (BHA). In this study, the potentials of BHA for dermal healing are assessed in vitro and in vivo. Consequently, BHA significantly promotes dermal healing relative to a commercial wound care product. By contrast, the “parent” partially de-acetylated LMW-HA (DHA) and the re-acetylated DHA (AHA) significantly delays wound closure, demonstrating the specificity of this N-acylation of LMW-HA in wound healing. Mechanistic studies reveal that the BHA-mediated therapeutic effect is achieved by targeting three phases of wound healing (i.e., inflammation, proliferation and maturation), demonstrating the significant potential of BHA for clinical translation in cutaneous wound healing.

Download Full-text

Effects of Tissucol™ and epsilon aminocaproic acid in the healing process following dental extraction in dehydrated rats

Brazilian Oral Research ◽

10.1590/s1806-83242006000100007 ◽

2006 ◽

Vol 20 (1) ◽

pp. 33-39 ◽

Cited By ~ 1

Author(s):

Tetuo Okamoto ◽

Maria Cristina Rosifini Alves-Rezende ◽

Carolina Chiantelli Cláudio ◽

Thaís da Silveira Rodrigues ◽

Roberta Okamoto

Keyword(s):

Water Deprivation ◽

Tooth Extraction ◽

Alveolar Bone ◽

Healing Process ◽

Aminocaproic Acid ◽

Fibrin Adhesive ◽

Group I ◽

Bone Healing Process ◽

Gingival Mucosa ◽

Epsilon Aminocaproic Acid

A histological study was conducted of the alveolar bone healing process following tooth extraction of dehydrated rats after the implantation of fibrin adhesive (TISSUCOL™) associated to previous irrigation of the wound with a 5% epsilon aminocaproic acid solution (EACA). Seventy two rats were used, divided into three groups receiving different treatments after the surgical procedure. In group I, the gingival mucosa was sutured after extraction of the right upper incisor. In groups II and III, chronic dehydration was produced by water deprivation for 9 days (3 days in the preoperative period and 6 days in the postoperative period). In the animals of Group II, after tooth extraction, the gingival mucosa was sutured in the same way as performed in group I. In group III, after extraction, the dental socket was irrigated with 5% EACA, followed by implantation of the fibrin adhesive (TISSUCOL™). The mucosa was sutured in the same way as performed in the other groups. At 3, 7, 15 and 21 postoperative days, the animals were sacrificed in number of 6 for each group. Specimens containing the dental socket were removed and fixed in 10% formalin and decalcified in an equal part formic acid and sodium citrate solution. After routine processing, the specimens were embedded in paraffin for microtomy. We obtained 6 µm semi-serial slices that were stained with hematoxylin and eosin for histological evaluation. The results showed that the water deprivation in the pre- and postoperative periods caused a delay in the alveolar bone healing process. The use of the fibrin adhesive (TISSUCOL™) produced an improvement in the fibrinolytic picture caused by dehydration.

Download Full-text

Histological and Histomorphometric Studies of the Effects of Hyaluronic Acid on Osseointegration of Titanium Implant in Rabbits

Journal of Baghdad College of Dentistry ◽

10.12816/0049745 ◽

2018 ◽

Vol 30 (2) ◽

pp. 10-16

Author(s):

Mohammad Hasan Mohammad ◽

Nada M. H. Al-Ghaban

Keyword(s):

Hyaluronic Acid ◽

Bone Formation ◽

Healing Process ◽

Pure Titanium ◽

Titanium Implant ◽

Commercially Pure Titanium ◽

Histomorphometric Analysis ◽

Natural Polymers ◽

Commercially Pure ◽

Significant Difference

Background: One of the unique prosthesis for tooth or teeth replacement is the dental implant. Our attempt is using a biomaterial system that is easily obtained and applicable and has the ability to provoke osteoinductive growth factor to enhance bone formation at the site of application. One of these natural polymers is hyaluronic acid. Material and methods: Sixty machined surface implants from commercially pure titanium rod inserted in thirty NewZealand rabbits. Two implants placed in both tibia of each rabbit. The animals scarified at 1, 2 and 4 weeks after implantation (10 rabbits for each interval). For all of animals the right tibia’s implant was control (uncoated) and the left one was experimental (coated with 0.1ml Hyaluronic acid gel). All sections have been stained with Haematoxylin and Eosin then they were histologically examined and assessed for histomorphometric analysis for counting of bone cells (osteoblast, osteocyte and osteoclast), cortical bone thickness, trabecular width, thread width and marrow space star volume (V*). Results: Histological findings for hyaluronic acid- coated titanium implant revealed an earlier bone formation, mineralization and maturation than that in control groups. Histomorphometric analysis for all bone parameters that examined in this study, showed highly significant difference between control and experimental groups in all healing intervals. Conclusion: Commercially pure titanium endosseous implants coated with hyaluronic acid may be osteocoductive thus accelerating healing process and enhancing osseointegration.

Download Full-text