Influence of extracellular matrix scaffolds on histological outcomes of regenerative endodontics in experimental animal models: a systematic review.

BACKGROUND: Decellularized extracellular matrix (dECM) from several tissue sources has been proposed as a promising alternative to conventional scaffolds used in regenerative endodontic procedures (REPs). This systematic review aimed to evaluate the histological outcomes of studies utilizing dECM-derived scaffolds for REPs and to analyse the contributing factors that might influence the nature of regenerated tissues. METHODS: The PRISMA 2020 guidelines were used. A search of articles published until April 2024 was conducted in Google Scholar, Scopus, PubMed and Web of Science databases. Additional records were manually searched in major endodontic journals. Original articles including histological results of dECM in REPs and in-vivo studies were included while reviews, in-vitro studies and clinical trials were excluded. The quality assessment of the included studies was analysed using the ARRIVE guidelines. Risk of Bias assessment was done using the (SYRCLE) risk of bias tool. RESULTS: Out of the 387 studies obtained, 17 studies were included for analysis. In most studies, when used as scaffolds with or without exogenous cells, dECM showed the potential to enhance angiogenesis, dentinogenesis and to regenerate pulp-like and dentin-like tissues. However, the included studies showed heterogeneity of decellularization methods, animal models, scaffold source, form and delivery, as well as high risk of bias and average quality of evidence. DISCUSSION: Decellularized ECM-derived scaffolds could offer a potential off-the-shelf scaffold for dentin-pulp regeneration in REPs. However, due to the methodological heterogeneity and the average quality of the studies included in this review, the overall effectiveness of decellularized ECM-derived scaffolds is still unclear. More standardized preclinical research is needed as well as well-constructed clinical trials to prove the efficacy of these scaffolds for clinical translation. OTHER: The protocol was registered in PROSPERO database #CRD42023433026. This review was funded by the Science, Technology and Innovation Funding Authority (STDF) under grant number (44426).

A radiographic and histological study to compare red (650 nm) versus near infrared (810 nm) diode lasers photobiomodulation for alveolar socket preservation.

Previous findings indicated that the laser photobiomodulation is more effective than the control or placebo in preserving the alveolar socket. This study aimed to compare two different lasers regarding their effectiveness in aiding alveolar socket preservation. Twenty extraction sockets were selected then divided into two equal groups. Group A was exposed to 650 nm Diode laser, and Group B to 810 nm Diode laser following the same protocol and parameters after a standard alveolar socket preservation procedure with collagen plug. Radiographic analysis with cone beam computed tomography was done to compare the alveolar bone surface area immediately after extraction and three months post-operatively, while bone samples collected before implant drilling were histologically examined for newly formed bone evaluation and histomorphometric analysis in terms of percentage of new bone surface area, percentage of unmineralized bone and finally, immunohistochemical analysis of Osteocalcin reaction surface area as well as optical density. Radiographically, infrared (810 nm) Diode effect on alveolar bone surface area has significantly exceeded the red laser, while histologically, red (650 nm) Diode has demonstrated statistical significance regarding all parameters; newly formed bone surface area percentage, unmineralized bone area percentage and finally Osteocalcin bone marker reaction surface area percentage and optical density. Under the specified conditions and laser parameters, photobiomodulation using the 810 nm Diode got the upper hand radiographically, yet histologically, the red 650 nm Diode managed to dominate all histological parameters when both employed as an adjunct to alveolar socket preservation procedures.

Effect of platelet rich plasma injection on bone formation in the expanded mid-palatal suture in rabbits: a randomized controlled animal study.

BACKGROUND: Mid-Palatal suture expansion needs long retention period due to delayed bone formation in the expanded suture. Platelet-rich plasma (PRP) is a concentrated source of growth factors which increase bone formation. The aim of this study was to evaluate the effect of PRP injection on bone formation in expanded mid palatal suture in rabbits. METHODS: In this prospective randomized controlled animal study, Twenty male rabbits (8-weeks-old) were subjected to mid-palatal expansion for 5 days. Animals were afterwards randomly divided into control group A & study group B. PRP was prepared and injected in the mid-palatal suture in animals belonging to group B only. After 6 weeks of retention, all animals were euthanized, and premaxillae were prepared for histological, histomorphometric and immunohistochemical analysis. Student t-test and paired t-test were used to compare the means of the two groups and within the same group respectively. Significance level set at p ≤ 0.05. RESULTS: Histomorphometric analysis revealed a significant increase (p < 0.001) in the mean percentage of new bone in the study group (14.4%) compared to the control (1.4%). Suture width in study group was significantly wider than the control group (278.8 ± 9µms and 120.4 ± 3.4µms, p < 0.001). There was a significant increase in vascular density in study group than control group (309 ± 65.34 and 243.86 ± 48.1, p = 0.021). Osteopontin immuno-expression revealed a significant increase in optical density in study group than control group (0.21 ± 0.02 & 0.12 ± 0.01, p < 0.001). CONCLUSIONS: In rabbit model, PRP injection can accelerate new bone formation in the expanded mid-palatal suture when compared to the control. This could hopefully result in a more stable midpalatal expansion and a reduced retention period.

Histological evaluation of the regenerative potential of a novel photocrosslinkable gelatin-treated dentin matrix hydrogel in direct pulp capping: an animal study.

BACKGROUND: To assess histologically the success of the pulp capping approach performed in traumatically exposed dogs' teeth using a novel injectable gelatin-treated dentin matrix light cured hydrogel (LCG-TDM) compared with LCG, MTA and TheraCal LC. METHODS: Sixty-four dogs' teeth were divided into two groups (each including 32 teeth) based on the post-treatment evaluation period: group I: 2 weeks and group II: 8 weeks. Each group was further subdivided according to the pulp capping material into four subgroups (n = 8), with subgroup A (light-cured gelatin hydrogel) as the control subgroup, subgroup B (LCG-TDM), subgroup C (TheraCal LC), and subgroup D (MTA). Pulps were mechanically exposed in the middle of the cavity floor and capped with different materials. An assessment of periapical response was performed preoperatively and at 8 weeks. After 2 and 8-week intervals, the dogs were sacrificed, and the teeth were stained with hematoxylin-eosin and graded by using a histologic scoring system. Statistical analysis was performed using the chi-square and Kruskal-Wallis tests (p = 0.05). RESULTS: All subgroups showed mild inflammation with normal pulp tissue at 2 weeks with no significant differences between subgroups (p ≤ 0.05), except for the TheraCal LC subgroup, which exhibited moderate inflammation (62.5%). Absence of a complete calcified bridge was reported in all subgroups at 2 weeks, while at 8 weeks, the majority of samples in the LCG-TDM and MTA-Angelus subgroups showed complete dentin bridge formation and absence of inflammatory pulp response with no significant differences between them (p ≤ 0.05). However, the formed dentin in the LCG-TDM group was significantly thicker, with layers of ordered odontoblasts identified to create a homogeneous tubular structure and numerous dentinal tubule lines suggesting a favourable trend towards dentin regeneration. TheraCal LC samples revealed a reasonably thick dentin bridge with moderate inflammation (50%) and LCG showed heavily fibrous tissue infiltrates with areas of degenerated pulp with no signs of hard tissue formation. CONCLUSIONS: LCG-TDM, as an extracellular matrix-based material, has the potential to regenerate dentin and preserve pulp vitality, making it a viable natural alternative to silicate-based cements for healing in vivo dentin defects in direct pulp-capping procedures.

Photocrosslinkable gelatin-treated dentin matrix hydrogel as a novel pulp capping agent for dentin regeneration: I. synthesis, characterizations and grafting optimization.

BACKGROUND: In recent years, treated dentin matrix (TDM) has been introduced as a bioactive hydrogel for dentin regeneration in DPC. However, no study has introduced TDM as a photocrosslinkable hydrogel with a natural photoinitiating system. Therefore, the present study aimed to explore the synthesis, characterizations and grafting optimization of injectable gelatin- glycidyl methacrylate (GMA)/TDM hydrogels as a novel photocrosslinkable pulp capping agent for dentin regeneration. METHODS: G-GMA/TDM hydrogel was photocrosslinked using a new two-component photoinitiating system composed of riboflavin as a photoinitiator under visible light and glycine as a first time coinitiator with riboflavin. The grafting reaction conditions of G-GMA/TDM e.g. GMA concentration and reaction time were optimized. The kinetic parameters e.g. grafting efficiency (GE) and grafting percentage (GP%) were calculated to optimize the grafting reaction, while yield (%) was determined to monitor the formation of the hydrogel. Moreover, G-GMA/TDM hydrogels were characterized by swelling ratio, degradation degree, and cytotoxicity. The instrumental characterizations e.g. FTIR, 1H-NMR, SEM and TGA, were investigated for verifying the grafting reaction. Statistical analysis was performed using F test (ANOVA) and Post Hoc Test (P = 0.05). RESULTS: The grafting reaction dramatically increased with an increase of both GMA concentration and reaction time. It was realized that the swelling degree and degradation rate of G-GMA/TDM hydrogels were significantly reduced by increasing the GMA concentration and prolonging the reaction time. When compared to the safe low and moderate GMA content hydrogels (0.048, 0.097 M) and shorter reaction times (6, 12, 24 h), G-GMA/TDM with high GMA contents (0.195, 0.391 M) and a prolonged reaction time (48 h) demonstrated cytotoxic effects against cells using the MTT assay. Also, the morphological surface of G-GMA/TDM freeze-dried gels was found more compacted, smooth and uniform due to the grafting process. Significant thermal stability was noticed due to the grafting reaction of G-GMA/TDM throughout the TGA results. CONCLUSIONS: G-GMA/TDM composite hydrogel formed by the riboflavin/glycine photoinitiating system is a potential bioactive and biocompatible system for in-situ crosslinking the activated-light pulp capping agent for dentin regeneration.

Periodontal changes following distraction osteogenesis in patients with cleft lip and palate: a clinical trial.

OBJECTIVES: To evaluate inflammatory mediator levels and periodontal changes following distraction osteogenesis (DO) in patients with cleft lip and palate (CLP) using mid-maxillary distraction (MMD). MATERIALS AND METHODS: A total of 20 healthy patients with CLP with Class III malocclusion were included. Segmental forward advancement of the anterior maxilla from the second premolars on both sides using DO was performed. A custom-made, tooth-borne distractor connecting buccal molar segments to the anterior maxilla was used for 7 days with 0.5-mm distraction for the first 2 days and then increased to 1 mm daily until overcorrection. Crevicular interleukin IL-1ß and tumor necrosis factor TNF-α levels were measured during distraction. Periodontal clinical parameters and indices were recorded at baseline and 3 and 6 months postoperatively. Soft tissue healing was evaluated histologically at 2 and 4 weeks after distraction. RESULTS: The periodontal parameters remained stable during the follow-up periods. Insignificant increases in the level of inflammatory cytokines compared with the control were observed. Histological findings revealed mild inflammatory and structural changes in the gingiva immediately after distraction, whereas regeneration was noticed after 4 weeks. CONCLUSIONS: MMD was an effective technique in treating patients with CLP, leading to new bone and soft tissue formation without significant detrimental effect on the periodontium of the adjacent teeth.

Comparison of Single Versus Multiple Low-Level Laser Applications on Bone Formation in Extraction Socket Healing in Rabbits (Histologic and Histomorphometric Study).

PURPOSE: This study evaluated the effect of low-level laser therapy (LLLT) on bone healing after tooth extraction in healthy rabbits and compared the effect between single and multiple doses of laser therapy. MATERIALS AND METHODS: Thirty-six New Zealand white male rabbits were randomly divided into 3 equal groups: a control (C) group, a single laser (SL) group, and a multiple laser (ML) group. The mandibular right first premolar was extracted. The SL group received a single dose of diode laser immediately after extraction. The ML group received a dose immediately after extraction and then every 72 hours for 12 days. The C group extraction sites were left untreated by laser. Eighteen animals were sacrificed at each of the experimental periods 3 and 6 weeks after extraction. The sockets were removed from the harvested mandibles and prepared for light microscopic examination and histomorphometric analysis. RESULTS: The SL and ML groups showed more bone formation and rapid maturation compared with the C group at 3 and 6 weeks postoperatively. At 6 weeks, the SL group showed the formation of compact bone. Furthermore, the ML group exhibited well-vascularized bone marrow spaces. Histomorphometric analysis showed an increase in the percentage of newly formed bone in the SL and ML groups compared with the C group. Moreover, the difference in the percentage of newly formed between the SL and ML groups was not statistically relevant. CONCLUSION: This rabbit model showed that single or multiple diode laser applications can be used to enhance bone formation after tooth extraction.