Skip to main content
Download PDF

Comparing the effect of using calcified autogenous nano dentin particles versus micro dentin particles in the healing of mandibular bony defects in New Zealand rabbits

BMC Research Notes volume 18, Article number: 125 (2025) Cite this article

Abstract

Objective

This study aimed to compare the regenerative effect of autogenous micro-dentin and nano-dentin particles on bone regeneration in rabbits’ mandibular defects. Sixty adult New Zealand rabbits were randomly divided into three groups: a control group, a micro-dentin group, and a nano-dentin group. A critical-sized bony defect was created at the lower border of the mandible. Bone regeneration was evaluated at two, four, and eight weeks using light microscopy, cone beam computed tomography (CBCT) scans, and histomorphometric analysis.

Results

Nano-dentin significantly enhanced bone density and defect closure, as evidenced by CBCT and histological analyses. At eight weeks, it promoted extensive new bone formation, nearly bridging the defect, with minimal residual graft material compared to the micro-dentin group. Histomorphometric analysis confirmed its superior osteogenic potential, demonstrating enhanced bone regeneration and graft resorption. These findings highlight nano-dentin as a highly effective biomaterial for mandibular bone repair.

Peer Review reports

Background

Bony defects in the oral and maxillofacial region arise from various etiologic factors, including tooth loss, periodontal disease, trauma, and pathological conditions such as cysts and oral cancer. These defects often result in the loss of both soft and hard tissues, leading to compromised function, aesthetics, and structural integrity of the jawbone [1, 2]. The severity and morphology of these defects vary, ranging from minor alveolar resorption to extensive bone loss affecting surrounding structures’ stability [3, 4]. Given these challenges, bone regeneration techniques are essential for restoring lost tissue and reestablishing a functional and aesthetically pleasing dentition [5]. Guided bone regeneration (GBR) [6, 7], bone grafting procedures [5, 8], and the use of biomaterials such as growth factors and scaffolds play a crucial role in stimulating new bone formation and improving treatment outcomes [9, 10].

Bone grafts should meet specific criteria for optimal performance, including an unlimited supply without harming the donor site, biocompatibility without immune rejection, and the ability to promote osteogenesis, osteoinduction, and osteoconduction [11]. Osteoinduction stimulates new bone formation by inducing osteocompetent cells, while osteoconduction supports bone growth along a scaffold. Additionally, grafts should allow rapid revascularization and be entirely replaced by new bone of comparable quality to the host tissue [12, 13].

Autogenous bone has long been regarded as the gold standard for grafting due to its biocompatibility and ability to promote osteoinduction and osteogenesis [5, 14]. It can be sourced from both intraoral locations (such as the chin symphysis and mandibular ramus) and extraoral sites (like the iliac crest and calvaria) [15,16,17]. However, numerous limitations and potential complications associated with its use. These limitations encompass the necessity for additional surgical interventions, which can lead to further complications, as well as aesthetic and functional impairments at the donor site [18, 19]. Consequently, these challenges have prompted researchers to investigate alternative treatment modalities.

Among these alternatives are allogenic, xenogenic, and alloplastic graft materials. However, these materials have drawbacks, including limited bone formation, increased risks of infectious diseases, prolonged healing times, and elevated costs [20]. An ideal substitute for autogenous bone grafts should effectively replicate its functional capabilities by stabilizing the initial blood clot and providing a biomechanically robust, three-dimensional scaffold that can release growth factors in a temporally and quantitatively appropriate manner. These characteristics facilitate cell migration, proliferation, and differentiation into osteoblasts [21].

Dentin, histologically, emerges as a natural tissue remarkably analogous to bone in developmental, physical, and chemical properties [22]. The composition of dentin mirrors that of bone, consisting of approximately 65% of inorganic material (hydroxyapatite) and 35% of organic material (collagen proteins and bone morphogenetic protein-BMP), making it similar in its three-dimensional scaffold architecture [23, 24]. Both components facilitate osteoconductive and osteoinductive processes [25, 26]. Furthermore, dentin particles contribute to the healing of mandibular bone defects by providing a scaffold and releasing growth factors that support bone regeneration. Dentin contains different combinations of bioactive molecules, including platelet-derived growth factor that enhances bone regeneration [27].

Moreover, dentin contains growth factors and non-collagenous proteins akin to those found in bone, such as insulin-like growth factor II (IGF-II), bone morphogenetic proteins (BMPs), transforming growth factor-beta (TGF-β), osteopontin, bone sialoproteins, dentin sialoproteins, osterix, and osteocalcin [28, 29]. Notably, dentin lacks the fat content and marrow spaces present in bone, simplifying its fabrication as a graft material [30].

Dentin has been reported as a grafting material in cases of alveolar socket preservation, correction of bone defects, and regeneration of periodontal defects [24, 31]. Nonetheless, undemineralized dentin does not readily induce new bone formation, necessitating partial demineralization as a preparatory step for its use as a graft material. This process, while effective, introduces its own set of challenges [32].

Biobased nanomaterials are naturally derived substances, including chitin, chitosan, starch, gellan gum, hyaluronic acid, hydroxyapatite, and polylactic co-glycolic acid. They are crucial in tissue engineering and are used for wound dressings, bone implants, scaffolds, cell seeding substrates, and skin disease treatments [33]. Nanomaterial research has gained traction in regenerative medicine in recent years, offering innovative possibilities. Nanoparticles can be synthesized from various materials, with multiple fabrication technologies available to produce nanomaterials featuring diverse nanotopographies [34].

This study evaluated the comparative effects of nano-dentin particles versus micro-dentin particles on the healing of mandibular bony defects in New Zealand white male rabbits.

Materials and methods

Animals

The study used sixty adult New Zealand white male rabbits with an average weight of 7–7.5 pounds. The animals were acquired from Tanta University, Egypt, and housed in the central animal facility at Tanta University, Tanta, Egypt. Ethical approval for the protocol was obtained, and the study was conducted following the animal welfare guidelines outlined by the Research Ethics Committee, Faculty of Dentistry, Tanta University # R-OB-11–22-3. Teeth were collected from six rabbits for graft material preparation, while the remaining rabbits were divided into three groups: a control group, a micro-dentin group, and a nano-dentin group, each consisting of eighteen animals.

Dentin powder preparation

Freshly extracted rabbit incisors were utilized to prepare dentin particles. The teeth were washed and cleaned using distilled water and 70% ethanol, followed by removing pulp tissue. Enamel and cementum tissues were removed by grinding the labial and lingual surfaces to isolate pure dentin. The dentin was crushed into small particles, washed multiple times with distilled water, and milled using a fast mill with ethanol as a solvent. The solution was filtered using filter paper, air-dried for 24 h, and sieved to obtain micro-dentin particles with a size of 500 μm. For nano-sized particles, the tooth powder in ethanol solution was milled for an additional 5 h, followed by rotation with a magnetic stirrer for 48 h. The resulting solution was air-dried for 24 h [18].

Sterilization of graft material

The prepared dentin particles were sterilized using gamma radiation at five kGy at the Atomic Energy Authority, Nasr City [25].

Characterization of dentin powder

The particle size and elemental composition, specifically the calcium and phosphate content, were confirmed using a scanning electron microscope (JSM 5200 LV SEM) and energy-dispersive X-ray analysis (EDX).

Surgical procedures

The animals were anesthetized via intramuscular injection of atropine sulfate (0.4 mL/kg), followed by ketamine hydrochloride 10% (0.5 mL/kg) and xylazine 2% (0.2 mL/kg). A submandibular approach was used to access the right lower mandibular border. The surgical site was shaved, disinfected with povidone-iodine, and incised layer by layer with careful hemostasis. The lower mandibular border was exposed, and the periosteum was retracted to create a standardized defect using a surgical bur attached to a high-torque surgical motor under saline irrigation. The defect measured 8 mm in length, 3 mm in width, and 4 mm in depth, just below the inferior alveolar nerve canal. Defects were left untreated in the control group (Fig. 1A), while the micro-dentin and nano-dentin groups received 200 mg of respective graft particles.

Fig. 1
figure 1

A Showing surgical defect at the lower border of the mandible. B Showing CBCT images of group 3 defect at 2nd week

Full size image

Radiographic analysis

Bone density at the defect sites was measured using a SCANORA® 3Dx CBCT unit (Soredex, Helsinki, Finland). CBCT images were exported in DICOM format, and SimPlant Pro 13.0 software (Materialise HQ, Leuven, Belgium) was used to calculate bone density in Hounsfield units (HU) (Fig. 1B).

Preparation of tissues

At designated intervals (2-, 4-, and 8-weeks post-implantation), the animals were euthanized via cervical dislocation, and tissue specimens were harvested. Specimens were processed for histological examination using hematoxylin and eosin (H&E) staining.

Histomorphometric analysis of newly formed bone

Prepared slides were examined under a light microscope (Leica DM500 with Leica ICC50 HD Camera system) at 40 × magnification. Images of H&E-stained sections were analyzed using ImageJ software (ImageJ 1.48s) to measure the newly formed bone area and graft material remnants. Six sections were selected per group, with approximately 200 μm between sections. For accuracy, the calculated areas were expressed in square micrometers [35].

Statistical analysis

Statistical analyses were conducted using ANOVA, independent t-tests, and Tukey tests. Results were reported as means and standard deviations. The statistical software SPSS 26 (SPSS Inc., Chicago, IL, USA) was used for data analysis. Significance levels were categorized as follows: very highly significant (p ≤ 0.001), highly significant (p ≤ 0.01), significant (p ≤ 0.05), and non-significant (p > 0.05).

Results

Characterization of dentin powder

Analysis of scanning electron microscopy (SEM) images revealed that the average particle sizes of the dentin powders were 2.68 ± 0.35 µm and 109.45 ± 11.25 nm for the micro-dentin and nano-dentin particles, respectively (Fig. 2). Energy-dispersive X-ray spectroscopy (SEM–EDX) analysis indicated calcium-to-phosphorus (Ca/P) ratios of 2.08 and 1.87 for the micro-dentin and nano-dentin particles, respectively.

Fig. 2
figure 2

SEM images of A micro-dentin and B nano-dentin particles, respectively

Full size image

Gross observations

All animals tolerated the surgical procedures well and demonstrated rapid recovery from anesthesia. Slight edema was observed bilaterally at the surgical sites. By the end of the first postoperative week, gross examination revealed evidence of surgical site healing in all animals, with no signs of infection.

CBCT scanning measurements

Cone beam computed tomography (CBCT) scans demonstrated progressive healing and repair of the lower border defects over time. Bone density within the groups increased gradually across the follow-up periods. Notably, there was a significant difference in bone density between the nano-dentin group and the other two groups, as summarized in Tables 1 and 2.

Table 1 Analyses newly formed bone density measurement through different durations in all groups
Full size table
Table 2 Multiple comparisons (Tukey test) show the difference between each two groups in all durations to measure newly formed bone density
Full size table

Light microscopy results

At two weeks postoperatively, light microscopic (LM) examination revealed that the control bone defects were mainly filled with connective tissue and fine bone trabeculae at the defect margins (Fig. 3). The defects in both the nano- and micro-dentin groups were demarcated and primarily filled with highly cellular granulation tissue, graft material, and newly formed bone trabeculae extending from the defect margins toward the center.

Fig. 3
figure 3

Microphotograph of the bony defect of group I (control group) (A, D) at two weeks filled with granulation tissue. No bony tissue is observed at the center of the bony defect (*). Microphotograph of the bony defect of group II (micro-dentin group) (B, E) and of the bony defect of group III (nano-dentin group) (C, F) showing graft material (arrow heads) with new bone formation (black arrows) at the defect margins that extends toward the defect center. (H&E, orig. mag., A, B, C × 40 & D, E, F × 100)

Full size image

The control group showed limited fine woven bone trabeculae formation at four weeks in certain defect areas. The micro-dentin group formed osteoid tissue around resorbed graft material, with new bone observed at the defect center. New bone trabeculae intermingled with the graft material in the nano-dentin group, bridging and effectively closing the defect surface. Resting lines and osteoclasts adjacent to pre-existing bone margins indicated active remodeling (Fig. 4).

Fig. 4
figure 4

Microphotograph of the bony defect of group I (control group) at 4 weeks with fine trabeculae of woven bone covering areas of the center of the defect (*) (A, D). In group II (micro-dentin) remnants of the graft material (arrow heads) is still evident with new bone trabeculae (black arrows) extending toward the center of the defect (B, E). In group III (C, F) the newly formed bone trabeculae form a bridge which closed the defect surface (NB), osteoclasts (yellow arrows) presence indicated remodelling of the old bone surface. Resting lines (red arrows) were evident denoting the successive increments of bone formation and reversal lines (white arrow). (H&E, orig. mag., A, B, C × 40 & D, E, F × 100)

Full size image

At eight weeks, the control group defects remained incompletely filled with bone. The micro-dentin group showed prominent new bone tissue formation, with reversal lines between old and new bone. However, significant graft material remained. In contrast, the nano-dentin group exhibited extensive new bone formation, nearly bridging and filling the defect area. Newly formed bone-enclosed osteocytes lined with active osteoblasts was evident. Residual graft material was present but in significantly smaller quantities than the micro-dentin group (Fig. 5).

Fig. 5
figure 5

Microphotograph of the bony defect of group I (control group) at 8 weeks showing no complete filling of the defect area (A). In group II (micro-dentin) remnants of the graft material (arrow heads) is still evident with new bone trabeculae extending toward the center of the defect and around the graft, with evident reversal lines (B). In group III (C) the newly formed bone is almost filling the defect area, NB; new bone (H&E, orig. mag., A, B, C × 40)

Full size image

Histomorphometric analysis

Histomorphometric analysis quantified new bone formation using mean and standard deviation (SD). Statistically significant differences were observed between groups at each interval and across intervals within each group. However, no significant difference was found between Groups I and II at the two- and eight-week intervals (Tables 3, 4, 5).

Table 3 Analyses measurement of newly formed bone through different durations in all groups
Full size table
Table 4 Differences between each type and two groups in all durations for measurement of newly formed bone using the Tukey test
Full size table
Table 5 Differences between each two durations in all groups for measurement of newly formed bone using the Tukey test
Full size table

Residual graft particles significantly decreased in Group III across all time points, with significant reductions observed between consecutive intervals, except between weeks 4 and 8 in Group II and between weeks 2 and 4 in Group III (Tables 6, 7).

Table 6 Analyses measurement of graft particle remnant through different durations in groups II and III
Full size table
Table 7 Multiple comparisons (Tukey test) is used to show the difference between each two durations for the remnant of graft particles in groups II and III
Full size table

Discussion

Various regenerative bone graft materials have been employed to address skeletal defects. An ideal bone graft material should exhibit osteoinductive and osteoconductive properties to facilitate effective bone regeneration [36]. Bone graft options include xenogeneic bone, allogenic bone, alloplastic materials, and bioactive glass. Degradable bioactive ceramics, such as tricalcium phosphate (TCP) and hydroxyapatite (HA), are commonly utilized [37].

However, calcium phosphate ceramics like TCP are associated with prolonged healing times due to their limited osteoinductive properties [38, 39] and high resorption rates [40]. Consequently, composites of HA and TCP are often developed, as HA is less prone to resorption and exhibits superior osteoinductive properties [41]. Dentin is a promising alternative graft material due to its unique inorganic composition, comprising a natural composite of calcium phosphate phases such as TCP, HA, octacalcium phosphate, dicalcium phosphate dihydrate, and amorphous calcium phosphate. Additionally, dentin's organic matrix predominantly comprises type I collagen and various growth factors, including BMPs, TGF-β, IGF, and IGF2 [42, 43].

Despite these advantages, dentin contains higher mineral and crystalline content than bone, which resists osteoclastic degradation. This hinders the release of entrapped growth factors, leading to slow resorption and suboptimal osteoconductivity [44]. Non-decalcified dentin blocks have shown delayed new bone formation, typically between 8–12 weeks post-implantation, necessitating dentin demineralization before use as a graft material. This aligns with findings by Mordenfeld et al. who reported a proportional relationship between the degree of dentin demineralization and the quantity of newly formed bone [45]. However, excessive exposure to decalcifying agents may compromise the bioactivity of growth factors essential for bone regeneration. Interestingly, fine-sized calcified dentin particles have been shown to induce bone formation within two weeks without osteoconductive delays, comparable to a completely demineralized dentin matrix [18].

Nanotechnology has been increasingly employed to enhance the physicochemical properties of scaffolds used in bone regeneration. By reducing material size to the nanoscale, the surface area-to-volume ratio is significantly increased, mimicking the hierarchical nanostructure of native bone tissue. Nanophase ceramics, such as nano-HA, are widely used bone substitutes with a high capacity to induce mineralization [46].

The present study aimed to evaluate the effects of nano-dentin versus micro-dentin particles on the healing of mandibular bony defects in New Zealand white rabbits. Nano-sized particles were chosen to emulate the nanoscale mineral crystals of bone, as their configuration and absorption mechanisms differ from those of larger crystals [47, 48]. SEM analysis confirmed particle sizes of 2.68 ± 0.35 µm and 109.45 ± 11.25 nm for micro- and nano-dentin particles, respectively.

Bone formation in the control group was minimal throughout the study, with incomplete defect healing observed at eight weeks, consistent with prior reports [49]. At two weeks, both micro- and nano-dentin groups demonstrated new bone trabeculae formation, predominantly at defect margins extending toward the center. By four weeks, graft material resorption had occurred, enhancing osteogenic cell proliferation and differentiation due to the release of growth factors from the resorbed dentin matrix [25, 50]. The resorption process also exposed collagen fibers, which served as scaffolds for cellular attachment, further promoting proliferation and differentiation [25]. Additionally, the sustained dissolution of graft materials released calcium and phosphate ions into the defect area, fostering osteogenic differentiation through ATP synthesis [49]. ATP metabolism into adenosine subsequently induced mesenchymal progenitors to differentiate into osteogenic cells via A2b adenosine receptors.

At eight weeks, the presence of reversal lines indicated advanced bone maturation, reflecting an active remodeling process [51]. Both micro- and nano-dentin groups exhibited minimal inflammatory cell infiltration across intervals, consistent with prior study demonstrating the low immunogenicity of dentin as a graft material [52]. The reduced inflammation likely contributed to favorable bone regeneration, scaffold resorption, and remodeling, mimicking a physiological rather than pathological healing process [53].

New bone deposition was observed around the graft material and defect margins in both experimental groups, demonstrating osteoinductive and osteoconductive properties. These findings align with those of Elkady et al. 2023 [35]. Quantitative analysis revealed significantly greater bone formation and density in the nano-dentin group than in the micro-dentin and control groups across all intervals. This enhanced osteoinductivity is attributed to the nano-calcium phosphate composite, which mimics the natural nanoscale of bone crystals. Nano-sized particles promote osteoblast adhesion, proliferation, and differentiation due to their unique surface properties, including increased surface area, phase content, roughness, and energy [54]. Additionally, the adsorption of vitronectin, which enhances osteoblast adhesion, is optimized at surface roughness below 100 nm [55]. The smaller particle size also facilitates cellular uptake via endocytosis, with lysosomal degradation releasing calcium ions that stimulate osteogenic differentiation [56].

Elgendy et al. [57] examined autogenous dentin nanoparticles versus allograft bone grafts in managing stage III periodontitis. Their findings indicated that nano-sized dentin exhibits unique characteristics attributed to its small dimensions and extensive specific surface area. Notably, this form of dentin enhances protein adsorption and promotes osteoblast adhesion. They concluded that autogenous dentin nanoparticles represent an effective and promising option for bone regeneration in intrabony defects.

The micro-dentin group showed insignificant graft remnant reduction over time, delaying decomposition due to the high crystalline content of dentin particles, as Kamal et al. 2017 noted [36]. Conversely, the nano-dentin group exhibited significantly reduced graft remnants due to the higher dissolution rate associated with smaller particle size and lower Ca/P ratio (1.87 vs. 2.08 for nano- and micro-dentin, respectively) [36, 58]. Smaller particles with higher solubility enhance ion exchange with the surrounding medium, accelerating recrystallization on the bone surface [58].

The accelerated degradation of nano-dentin facilitated the rapid release, absorption, and reconstruction of calcium and phosphate ions, promoting bone formation and calcification [59]. Calcium ions activate ERK1/2 and PI3K/Akt pathways, enhancing osteoblast function and lifespan [60, 61]. Furthermore, calcium ions regulate osteoclast activity, and phosphate ions enhance BMP expression, IGF-1 activation, and ERK1/2 signaling, promoting osteogenic differentiation [62]. Phosphate also inhibits osteoclast differentiation via RANK-ligand signaling feedback [63].

Mohammed and Rejeb [64] researched using milled teeth in nanoparticle form as a substitute for bone grafts in rabbits. Histological examinations revealed that the nanoparticle group displayed moderate vascularity and granulation tissue after three days, with new blood vessel formation by the seventh day. By the 14th day, the inflammation had significantly decreased, and by the 28th day, there was notable angiogenesis and moderate development of osteoid tissue. The study concluded that nanoparticles derived from milled teeth promote bone repair.

Limitations

Despite the strengths of this study, several limitations should be acknowledged:

  • Animal model: The use of a rabbit model, while providing valuable insights into bone regeneration, may not fully replicate human biological responses, potentially limiting the generalizability of the findings. However, rabbits are widely used in bone regeneration research due to their rapid bone turnover and anatomical suitability for controlled defect studies [65, 66].

  • Sterilization process: Gamma radiation was employed to sterilize the graft material, but its potential impact on bioactivity cannot be entirely ruled out. Although previous studies suggest minimal effects on regenerative properties, further investigation is warranted to confirm its influence on clinical applications [67,68,69].

These limitations should be considered when interpreting the study results and designing future research.

Conclusion

The findings of this study demonstrate that nano-dentin particles effectively address the limitations associated with dentin as a bone graft material, such as low solubility and poor osteoinductivity. The application of nanotechnology offers a promising avenue for developing advanced biomaterials with enhanced efficiency and functionality. These nanostructured biomaterials can respond dynamically to changes in their immediate environment, optimizing bone regeneration. Such advancements have significant potential for improving clinical outcomes of regenerative medicine and bone tissue engineering.

Future research should optimize nano-dentin grafts for better osteogenesis and clinical use. Testing in larger models and enhancing bioactivity with coatings or growth factors will aid translation to human applications. Further studies on immunogenicity and sterilization refinements will improve biocompatibility and effectiveness.

Data availability

All data generated or analysed during this study are included in this published article

Abbreviations

Ca/P:

Calcium-to-Phosphorus Ratio

CBCT:

Cone Beam Computed Tomography

DICOM:

Digital Imaging and Communications in Medicine

EDX:

Energy-Dispersive X-ray Analysis

H&E:

Hematoxylin and Eosin

HU:

Hounsfield units

LM:

Light Microscopy

SEM:

Scanning Electron Microscopy

SEM–EDX:

Scanning electron microscopy with energy-dispersive X-ray spectroscopy

SPSS:

Statistical Package for the Social Sciences

References

  1. Michaud DS, Fu Z, Shi J, et al. Periodontal disease, tooth loss, and cancer risk. Epidemiol Rev. 2017;39:49–58.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Tan B, Tang Q, Zhong Y, et al. Biomaterial-based strategies for maxillofacial tumour therapy and bone defect regeneration. Int J Oral Sci. 2021;13:9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hienz SA, Paliwal S, Ivanovski S. Mechanisms of bone resorption in periodontitis. J Immunol Res. 2015;2015: 615486.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wang Z, Ma Z, Yang C. Alveolar bone defects around mandibular anterior teeth in class I, II, and III malocclusions: a retrospective CBCT evaluation. Front Oral Maxillofac Med. 2023;5:2.

    Article  Google Scholar 

  5. Elboraey MO, Alqutaibi AY, Aboalrejal AN, et al. Regenerative approaches in alveolar bone augmentation for dental implant placement: techniques, biomaterials, and clinical decision-making: a comprehensive review. J Dent. 2025;154:105612.

    Article  CAS  PubMed  Google Scholar 

  6. Urban IA, Montero E, Amerio E, et al. Techniques on vertical ridge augmentation: indications and effectiveness. Periodontology 2000. 2000;93:153–82.

    Article  Google Scholar 

  7. Al-Dubai SAS, Abdel-Rahman FH, Ahmed W, et al. Comparison between modified bone-splitting technique and distraction osteogenesis in horizontal alveolar ridge expansion: randomized clinical study. J Contemp Dent Pract. 2022;23:1008–15.

    PubMed  Google Scholar 

  8. Sethi A, Kaus T. Ridge augmentation using mandibular block bone grafts: preliminary results of an ongoing prospective study. Int J Oral Maxillofac Implants. 2001;16:378.

    CAS  PubMed  Google Scholar 

  9. Chen R, Wang J, Liu C. Biomaterials act as enhancers of growth factors in bone regeneration. Adv Func Mater. 2016;26:8810–23.

    Article  CAS  Google Scholar 

  10. Dang Y, Zhang Y, Luo G, et al. The decisive early phase of biomaterial-induced bone regeneration. Appl Mater Today. 2024;38: 102236.

    Article  Google Scholar 

  11. Ferraz MP. Bone grafts in dental medicine: an overview of autografts, allografts and synthetic materials. Materials. 2023;16:4117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lee SS, Huber S, Ferguson SJ. Comprehensive in vitro comparison of cellular and osteogenic response to alternative biomaterials for spinal implants. Mater Sci Eng C. 2021;127: 112251.

    Article  CAS  Google Scholar 

  13. Oryan A, Alidadi S, Moshiri A, et al. Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res. 2014;9:1–27.

    Article  Google Scholar 

  14. Sakkas A, Wilde F, Heufelder M, et al. Autogenous bone grafts in oral implantology—is it still a “gold standard”? A consecutive review of 279 patients with 456 clinical procedures. Int J Implant Dent. 2017;3:1–17.

    Article  Google Scholar 

  15. Dellavia C, Giammattei M, Carmagnola D, et al. Iliac crest fresh-frozen allografts versus autografts in oral pre-prosthetic bone reconstructive surgery: histologic and histomorphometric study. Implant Dent. 2016;25:731–8.

    Article  PubMed  Google Scholar 

  16. Restoy-Lozano A, Dominguez-Mompell P-L, Infante-Cossio P, et al. Calvarial bone grafting for three-dimensional reconstruction of severe maxillary defects: a case series. Int J Oral Maxillofac Implants. 2015;30:880.

    Article  PubMed  Google Scholar 

  17. Bianchi S, Bernardi S, Mattei A, et al. Morphological and biological evaluations of human periodontal ligament fibroblasts in contact with different bovine bone grafts treated with low-temperature deproteinisation protocol. Int J Mol Sci. 2022;23:5273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Saeed KW, Gataa IS, Garib BT. Fine calcified human dentin particles grafts in experimental bone defects in rabbit femur accelerate bone healing and maturation. Int J Dental Sci Res. 2015;2:8–13.

    Article  Google Scholar 

  19. Alqutaibi AY, Alnazzawi AA, Farghal A. Autogenous dentin grafts have comparable short-term outcomes to other graft materials regarding implant stability, preimplant marginal bone loss, and complication rate. J Evid Based Dental Pract. 2023;23: 101844.

    Article  Google Scholar 

  20. Goutam M, Batra N, Jyothirmayee K, et al. A comparison of xenograft graft material and synthetic bioactive glass allograft in immediate dental implant patients. J Pharm Bioallied Sci. 2022;14:S980–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kim YK, Lee J, Um IW, et al. Tooth-derived bone graft material. J Korean Assoc Oral Maxillofac Surg. 2013;39:103–11.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wang T, Guo Y. The host response to autogenous, allogeneic, and xenogeneic treated dentin matrix/demineralized dentin matrix-oriented tissue regeneration. Tissue Eng Part B Rev. 2024;30:74–81.

    Article  CAS  PubMed  Google Scholar 

  23. Caruso S, Bernardi S, Pasini M, et al. The process of mineralisation in the development of human tooth. Eur J Paediatr Dent. 2016;17:322–6.

    CAS  PubMed  Google Scholar 

  24. Bianchi S, Mancini L, Torge D, et al. Bio-morphological reaction of human periodontal ligament fibroblasts to different types of dentinal derivates: in vitro study. Int J Mol Sci. 2021;22:8681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Li J, Yang J, Zhong X, et al. Demineralized dentin matrix composite collagen material for bone tissue regeneration. J Biomater Sci Polym Ed. 2013;24:1519–28.

    Article  CAS  PubMed  Google Scholar 

  26. Bono N, Tarsini P, Candiani G. BMP-2 and type I collagen preservation in human deciduous teeth after demineralization. J Appl Biomater Funct Mater. 2019;17:2280800018784230.

    PubMed  Google Scholar 

  27. Bianchi S, Torge D, Rinaldi F, et al. Platelets’ role in dentistry: from oral pathology to regenerative potential. Biomedicines. 2022;10:218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kinney J, Marshall S, Marshall G. The mechanical properties of human dentin: a critical review and re-evaluation of the dental literature. Crit Rev Oral Biol Med. 2003;14:13–29.

    Article  CAS  PubMed  Google Scholar 

  29. Kruzic J, Ritchie R. Fatigue of mineralized tissues: cortical bone and dentin. J Mech Behav Biomed Mater. 2008;1:3–17.

    Article  CAS  PubMed  Google Scholar 

  30. Inchingolo AM, Patano A, Pede C, et al. Autologous tooth graft: innovative biomaterial for bone regeneration. Tooth transformer® and the role of microbiota in regenerative dentistry, a systematic review. J Funct Biomater. 2023;14:132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Graziano A, Carinci F, Scolaro S, et al. Periodontal tissue generation using autologous dental ligament micro-grafts: case report with 6 months follow-up. Ann Oral Maxillofac Surg. 2013;1:20.

    Article  Google Scholar 

  32. Deng M, James R, Laurencin CT, et al. Nanostructured polymeric scaffolds for orthopaedic regenerative engineering. IEEE Trans Nanobiosci. 2012;11:3–14.

    Article  Google Scholar 

  33. Niranjan MK, Baghel K, Azam Z. Biobased nanomaterials in regenerative medicines. In: Biobased nanomaterials: applications in biomedicine, food industry, agriculture, and environmental sustainability. Singapore: Springer; 2024. p. 223–48.

    Chapter  Google Scholar 

  34. Govahi M, Azam AN, Tabatabai SH, et al. Comparing the effect of human wisdom teeth pulverized in micron and nano particle dimensions as grafting material in healing of tibial bone defect. Bali Med J. 2016. https://doiorg.publicaciones.saludcastillayleon.es/10.15562/bmj.v5i1.347.

    Article  Google Scholar 

  35. Elkady E, Nour El-den R, Atiba A, et al. Comparing the effect of demineralized versus hybrid dentin matrices on inducing bone regeneration in New Zealand white rabbits’ Mandibular defect. J Stomatol Oral Maxillofac Surg. 2023;124:101346.

    Article  PubMed  Google Scholar 

  36. Kamal M, Andersson L, Tolba R, et al. Bone regeneration using composite non-demineralized xenogenic dentin with beta-tricalcium phosphate in experimental alveolar cleft repair in a rabbit model. J Transl Med. 2017;15:263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ashfaq R, Kovács A, Berkó S, et al. Developments in alloplastic bone grafts and barrier membrane biomaterials for periodontal guided tissue and bone regeneration therapy. Int J Mol Sci. 2024;25:7746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kang MS, Lee N-H, Singh RK, et al. Nanocements produced from mesoporous bioactive glass nanoparticles. Biomaterials. 2018;162:183–99.

    Article  CAS  PubMed  Google Scholar 

  39. Araújo M, Mendes V, Chattopadhyay P, et al. Low-temperature particulate calcium phosphates for bone regeneration. Clin Oral Implant Res. 2010;21:632–41.

    Article  Google Scholar 

  40. Cordaro L, Bosshardt DD, Palattella P, et al. Maxillary sinus grafting with Bio-Oss® or straumann® bone ceramic: histomorphometric results from a randomized controlled multicenter clinical trial. Clin Oral Implant Res. 2008;19:796–803.

    Article  Google Scholar 

  41. Kattimani VS, Kondaka S, Lingamaneni KP. Hydroxyapatite—past, present, and future in bone regeneration. Bone Tissue Regen Insights. 2016;7:BTRI.S36138.

    Article  Google Scholar 

  42. He P, Zheng L, Zhou X. IGFs in dentin formation and regeneration: progress and remaining challenges. Stem Cells Int. 2022;2022:3737346.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Zhang S, Li X, Qi Y, et al. Comparison of autogenous tooth materials and other bone grafts. Tissue Eng Regen Med. 2021;18:327–41.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Janjua OS, Qureshi SM, Shaikh MS, et al. Autogenous tooth bone grafts for repair and regeneration of maxillofacial defects: a narrative review. Int J Environ Res Public Health. 2022;19:3690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mordenfeld A, Hallman M, Lindskog S. Tissue reactions to subperiosteal onlays of demineralized xenogenous dentin blocks in rats. Dent Traumatol. 2011;27:446–51.

    Article  PubMed  Google Scholar 

  46. Lyons JG, Plantz MA, Hsu WK, et al. Nanostructured biomaterials for bone regeneration. Front Bioeng Biotechnol. 2020;8:922.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Perez RA, Won J-E, Knowles JC, et al. Naturally and synthetic smart composite biomaterials for tissue regeneration. Adv Drug Deliv Rev. 2013;65:471–96.

    Article  CAS  PubMed  Google Scholar 

  48. Wang Q, Yan J, Yang J, et al. Nanomaterials promise better bone repair. Mater Today. 2016;19:451–63.

    Article  CAS  Google Scholar 

  49. Al-Asfour A, Andersson L, Kamal M, et al. New bone formation around xenogenic dentin grafts to rabbit tibia marrow. Dent Traumatol. 2013;29:455–60.

    Article  CAS  PubMed  Google Scholar 

  50. Barradas AM, Fernandes HA, Groen N, et al. A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells. Biomaterials. 2012;33:3205–15.

    Article  CAS  PubMed  Google Scholar 

  51. Hong I, Khalid AW, Pae HC, et al. Diverse patterns of bone regeneration in rabbit calvarial defects depending on the type of collagen membrane. J Periodontal Implant Sci. 2021;51:40–52.

    Article  CAS  PubMed  Google Scholar 

  52. Andersson L. Dentoalveolar ankylosis and associated root resorption in replanted teeth. Experimental and clinical studies in monkeys and man. Swed Dent J Suppl. 1988;56:1–75.

    CAS  PubMed  Google Scholar 

  53. Schnettler R, Stahl JP, Alt V, Pavlidis T, Dingeldein E, Wenisch S. Calcium phosphate-based bone substitutes. Eur J Trauma. 2004;30:219–29.

    Article  Google Scholar 

  54. Mendes VC, Moineddin R, Davies JE. The effect of discrete calcium phosphate nanocrystals on bone-bonding to titanium surfaces. Biomaterials. 2007;28:4748–55.

    Article  CAS  PubMed  Google Scholar 

  55. Hench LL. Bioceramics: from concept to clinic. J Am Ceram Soc. 1991;74(7):1487–51.

    Article  CAS  Google Scholar 

  56. LeGeros RZ, Ben-Nissan B. Introduction to synthetic and biologic apatites. Adv Calcium Phosphate Biomater. 2014. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/978-3-642-53980-0_1.

    Article  Google Scholar 

  57. Elgendy EA, Elgendy AM, ElBorady OM. Clinical And radiographic assessment of autogenous dentin nanoparticles in treatment of stage iii periodontitis: a split-mouth clinical study. J Pak Med Assoc. 2023;73:310–6.

    Article  Google Scholar 

  58. Zhang Y, Shao H, Lin T, et al. Effect of Ca/P ratios on porous calcium phosphate salt bioceramic scaffolds for bone engineering by 3D gel-printing method. Ceram Int. 2019;45:20493–500.

    Article  CAS  Google Scholar 

  59. Liu D, Genetos DC, Shao Y, et al. Activation of extracellular-signal regulated kinase (ERK1/2) by fluid shear is Ca2+-and ATP-dependent in MC3T3-E1 osteoblasts. Bone. 2008;42:644–52.

    Article  CAS  PubMed  Google Scholar 

  60. Danciu TE, Adam RM, Naruse K, et al. Calcium regulates the PI3K-Akt pathway in stretched osteoblasts. FEBS Lett. 2003;536:193–7.

    Article  CAS  PubMed  Google Scholar 

  61. Kuroda Y, Hisatsune C, Nakamura T, et al. Osteoblasts induce Ca2+ oscillation-independent NFATc1 activation during osteoclastogenesis. Proc Natl Acad Sci USA. 2008;105:8643–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Khoshniat S, Bourgine A, Julien M, et al. The emergence of phosphate as a specific signaling molecule in bone and other cell types in mammals. Cell Mol Life Sci. 2011;68:205–18.

    Article  CAS  PubMed  Google Scholar 

  63. Tada H, Nemoto E, Foster BL, et al. Phosphate increases bone morphogenetic protein-2 expression through cAMP-dependent protein kinase and ERK1/2 pathways in human dental pulp cells. Bone. 2011;48:1409–16.

    Article  CAS  PubMed  Google Scholar 

  64. Mohammed SM, Rejeb AF. The use of nanoparticle form of milled teeth as a bone graft substitute in rabbits. Int J Health Sci. 2022;6:6321–32.

    Article  Google Scholar 

  65. Pripatnanont P, Nuntanaranont T, Vongvatcharanon S. Proportion of deproteinized bovine bone and autogenous bone affects bone formation in the treatment of calvarial defects in rabbits. Int J Oral Maxillofac Surg. 2009;38:356–62.

    Article  CAS  PubMed  Google Scholar 

  66. Castaneda S, Largo R, Calvo E, et al. Bone mineral measurements of subchondral and trabecular bone in healthy and osteoporotic rabbits. Skelet Radiol. 2006;35:34–41.

    Article  CAS  Google Scholar 

  67. de Sousa Iwamoto LA, Duailibi MT, Iwamoto GY, et al. Evaluation of ethylene oxide, gamma radiation, dry heat and autoclave sterilization processes on extracellular matrix of biomaterial dental scaffolds. Sci Rep. 2022;12:4299.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Ayask HK, Sasani N, Hassanzadeh H, et al. Investigating the effects of gamma irradiation on osteogenic properties of OsvehOss synthetic bone graft substitutes as orthopedic implant materials. J Cell Mol Res. 2024;16:25–35.

    Google Scholar 

  69. Ku J-K, Kim I-H, Um I-W, et al. Effect of gamma irradiation on the osteoinductivity of demineralized dentin matrix for allografts: a preliminary study. J Funct Biomater. 2022;13:14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This study did not receive any funds

Author information

Authors and Affiliations

  1. Oral Biology Department, Faculty of Dentistry, Tanta University, Tanta, Egypt

    Sarah Yasser, Hasnaa Fouad & Reda G. Saleh

  2. Oral and Maxillofacial Surgery Department, Faculty of Oral and Dental Medicine, Qena University, Qena, Egypt

    Altaib Abd al razik Mohammed

  3. Dental Biomaterials Department, Faculty of Dentistry, Tanta University, Tanta, Egypt

    Samy El-Safty

  4. Removable Prosthodontics Department, Faculty of Dental Medicine, AL-Azhar University, Cairo, Egypt

    Ahmed Shon

  5. Dental Department, Al Mouwasat Hospital, Al Madinah Al Munawwarah, Al-Madinah, Saudi Arabia

    Ahmed Shon

  6. Prosthodontic Department, Faculty of Dentistry, Ibb University, Ibb, Yemen

    Redhwan Saleh Al-Gabri & Ahmed Yaseen Alqutaibi

  7. Substitutive Dental Science Department, College of Dentistry, Taibah University, Al-Madinah, Saudi Arabia

    Ahmed Yaseen Alqutaibi

  8. Oral Biology Department, College of Oral and Dental Medicine, Alsalam University, Tanta, Egypt

    Hasnaa Fouad

Authors
  1. Sarah Yasser
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Altaib Abd al razik Mohammed
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Samy El-Safty
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Ahmed Shon
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Redhwan Saleh Al-Gabri
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Ahmed Yaseen Alqutaibi
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Hasnaa Fouad
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Reda G. Saleh
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Sarah Yasser, Altaib Abd elrazik Mohammed , Samy El-Safty, Hasnaa Fouad and Reda G. Saleh; Conception, Design of the Study and Acquisition of Data. Ahmed Shon , Radhwan Saleh Algabri and Ahmed Yaseen Alqutaibi; Analysis and Interpretation of Data and Drafting the Manuscript.

Corresponding author

Correspondence to Redhwan Saleh Al-Gabri.

Ethics declarations

Ethics approval and consent to participate

Ethical clearance was obtained from the Ethics Review Committee of the Faculty of Dentistry, Tanta University, (Approval No. R-OB-11–22-3).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yasser, S., Mohammed, A.A., El-Safty, S. et al. Comparing the effect of using calcified autogenous nano dentin particles versus micro dentin particles in the healing of mandibular bony defects in New Zealand rabbits. BMC Res Notes 18, 125 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13104-025-07191-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13104-025-07191-6

Keywords

BMC Research Notes

ISSN: 1756-0500

Contact us