Comparison of Bone Substitutes in a Tibia Defect Model in Wistar-Rats

Various bone graft substitutes were used in clinical practise in the treatment of bone defects after trauma or osteoporosis. Many synthetic biomaterials were developed in recent years primarily based on hydroxyapatite (HA). NanoBone® is a nanocrystalline hydroxyapatite (HA) embedded in a porous matrix of silica (SiO2). The ratio of HA:SiO2 varied between 76:24 (wt%; NanoBone®) and 61:39 (wt%; Nanobone® S). The two bone substitutes NB and NB S and a natural bovine bone substitute Bio-Oss® (BO) were evaluated by means of implantation in the tibia of the rat. The aim of this study was to analyze the remodelling process and to measure new bone formation and degradation after implantation of these biomaterials. A tibia defect model was used for all investigations with testing periods of 12, 21 and 84 days. (n=5 for each time point). The results showed, that all bone grafts were well accepted by the host tissue without inflammatory reactions. In comparison to the biomaterial BO, NanoBone® and NanoBone® S were quickly degraded, whereas autologous proteins were incorporated into nanopores. New bone formation was statistically higher in NanoBone® S compared to Bio-Oss® in defect area after 84 days implantation. The presence of osteoclasts in tissue sections were demonstrated by TRAP- and ED1-immunohistology.

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Horizontal Augmentation of Chronic Mandibular Defects by the Guided Bone Regeneration Approach: A Randomized Study in Dogs

Materials ◽

10.3390/ma15010238 ◽

2021 ◽

Vol 15 (1) ◽

pp. 238

Author(s):

Anton Friedmann ◽

Stefan Fickl ◽

Kai R. Fischer ◽

Milad Dalloul ◽

Werner Goetz ◽

...

Keyword(s):

Bone Formation ◽

Randomized Study ◽

Bone Substitutes ◽

Blue Staining ◽

Collagen Membrane ◽

Bovine Bone ◽

New Bone Formation ◽

Native Bone ◽

Pin Fixation ◽

Group B

Various biomaterial combinations have been studied focusing on their ability to stabilize blood clots and maintain space under soft tissue to support new bone formation. A popular combination is Deproteinized Bovine Bone Mineral (DBBM) placed with a native collagen membrane (NCM) tacked to native bone. In this study, we compared the outcome of this treatment option to those achieved with three different graft/membrane combinations with respect to total newly occupied area and the mineralized compound inside. After bi-lateral extraction of two mandibular premolars in five adult beagles L-shaped alveolar defects were created. A total of 20 defects healed for 6 weeks resulting in chronic type bone defects. At baseline, four options were randomly allocated to five defects each: a. DBBM + NCM with a four-pin fixation across the ridge; b. DBBM + RCLC (ribose cross-linked collagen membrane); c. DBBM + NPPM (native porcine pericardium membrane); and d. Ca-sulfate (CS) + RCLC membrane. Membranes in b/c/d were not fixed; complete tensionless wound closure was achieved by CAF. Termination after 3 months and sampling followed, and non-decalcified processing and toluidine blue staining were applied. Microscopic images obtained at standardized magnification were histomorphometrically assessed by ImageJ software (NIH). An ANOVA post hoc test was applied; histomorphometric data are presented in this paper as medians and interquartile ranges (IRs). All sites healed uneventfully, all sites were sampled and block separation followed before Technovit embedding. Two central sections per block for each group were included. Two of five specimen were lost due to processing error and were excluded from group b. New bone area was significantly greater for option b. compared to a. (p = 0.001), c. (p = 0.002), and d. (p = 0.046). Residual non-bone graft area was significantly less for option d. compared to a. (p = 0.026) or c. (p = 0.021). We conclude that collagen membranes with a prolonged resorption/barrier profile combined with bone substitutes featuring different degradation profiles sufficiently support new bone formation. Tacking strategy/membrane fixation appears redundant when using these biomaterials.

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Bovine Anorganic Bone Graft Associated with Platelet-Rich Plasma: Histologic Analysis in Rabbit Calvaria

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-09-00091.1 ◽

2011 ◽

Vol 37 (5) ◽

pp. 511-518 ◽

Cited By ~ 4

Author(s):

Flaviana Soares Rocha ◽

Lara Maria Alencar Ramos ◽

Jonas Dantas Batista ◽

Darceny Zanetta-Barbosa ◽

Eloísa Amália Vieira Ferro ◽

...

Keyword(s):

Bone Formation ◽

Platelet Rich Plasma ◽

Fibrous Tissue ◽

Giant Cells ◽

Autogenous Bone ◽

Bone Lesions ◽

Bovine Bone ◽

New Bone Formation ◽

Significant Difference ◽

Defect Area

Autogenous bone tissue has regeneration potential; however, this capacity may not be sufficient in larger bone defects. The aim of this study is to histologically evaluate anorganic bovine bone grafts (GenOx Inorg) with or without platelet-rich plasma (PRP). Two bone lesions were created in calvaria of 12 rabbits. The 24 surgical lesions were separated into 3 groups: coagulous, anorganic, and anorganic with PRP. At the 4-week time point, the animals were euthanized and the grafted area removed, fixed in formalin 10% with phosphate buffered saline, 0.1 M, and embedded in paraffin. The histologic parameters analyzed were new bone filling the defect area, presence of giant cells and particles of the graft, and new bone formation associated with the particles. In the coagulous group, defects were filled with fibrous tissue that attached the periosteum and little bone neoformation in the periphery. In anorganic groups with or without PRP, little new bone formation in the periphery of the defect was observed; however, in the center of some defects there was new bone. Moderate presence of giant cells and little new bone formation was associated with the innumerous graft particles. Histologic results revealed no statistically significant differences among the defects new bone fill between the studied groups (P = .64). There was no significant difference in the number of giant cells (P = .60), graft particles (P = .46), and new bone formation around graft particles (P = .26), whether PRP was added or not. Anorganic bone, isolated or mixed with PRP, was biocompatible and osteoconductive, while maintaining bone volume.

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Biomimetic Octacalcium Phosphate Bone Has Superior Bone Regeneration Ability Than Xenogeneic or Synthetic Bone

10.20944/preprints202109.0166.v1 ◽

2021 ◽

Author(s):

Jooseong Kim ◽

Sukyoung Kim ◽

In-Hwan Song

Keyword(s):

Bone Formation ◽

Bone Regeneration ◽

Mass Production ◽

Bone Substitutes ◽

Octacalcium Phosphate ◽

Regeneration Ability ◽

Bovine Bone ◽

New Bone Formation ◽

Apatite Crystals ◽

Biological Apatite

Octacalcium phosphate (OCP) is a precursor of biological apatite crystals that has attracted attention as a possible bone substitute. On the other hand, few studies have examined this material at the experimental level due to the limitations of OCP mass production. Recently, mass production technology of OCP was developed, and the launch of OCP bone substitutes is occurring. In this study, the bone regeneration capacity of OCP products was compared with two of the most clinically used materials: heat-treated bovine bone (BHA) and sintered biphasic calcium phosphate (BCP). Twelve rabbits were used, and defects in each tibia were filled with OCP, BHA, BCP, and left unfilled as control (CON). The tibias were harvested at 4 and 12 weeks, and 15 μm slides were prepared using the diamond grinding method after being embedded in resin. Histological and histomorphometric analyses were performed to evaluate the bone regeneration ability and mechanism. The OCP showed significantly higher resorption and new bone formation in both periods analysed (p<0.05). Overall, OCP bone substitutes can enhance bone regeneration significantly by activating osteoblasts and a rapid phase transition of OCP crystals to biological apatite crystals (mineralisation), as well as providing additional space for new bone formation by rapid resorption.

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Biomimetic Octacalcium Phosphate Bone Has Superior Bone Regeneration Ability Compared to Xenogeneic or Synthetic Bone

Materials ◽

10.3390/ma14185300 ◽

2021 ◽

Vol 14 (18) ◽

pp. 5300

Author(s):

Jooseong Kim ◽

Sukyoung Kim ◽

Inhwan Song

Keyword(s):

Bone Formation ◽

Bone Regeneration ◽

Mass Production ◽

Bone Substitutes ◽

Octacalcium Phosphate ◽

Regeneration Ability ◽

Bovine Bone ◽

New Bone Formation ◽

Apatite Crystals ◽

Biological Apatite

Octacalcium phosphate (OCP) is a precursor of biological apatite crystals that has attracted attention as a possible bone substitute. On the other hand, few studies have examined this material at the experimental level due to the limitations on OCP mass production. Recently, mass production technology of OCP was developed, and the launch of OCP bone substitutes is occurring. In this study, the bone regeneration capacity of OCP products was compared with two of the most clinically used materials: heat-treated bovine bone (BHA) and sintered biphasic calcium phosphate (BCP). Twelve rabbits were used, and defects in each tibia were filled with OCP, BHA, BCP, and left unfilled as control (CON). The tibias were harvested at 4 and 12 weeks, and 15 μm slides were prepared using the diamond grinding method after being embedded in resin. Histological and histomorphometric analyses were performed to evaluate the bone regeneration ability and mechanism. The OCP showed significantly higher resorption and new bone formation in both periods analysed (p < 0.05). Overall, OCP bone substitutes can enhance bone regeneration significantly by activating osteoblasts and a rapid phase transition of OCP crystals to biological apatite crystals (mineralization), as well as providing additional space for new bone formation by rapid resorption.

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Mechanistic Illustration: How Newly-Formed Blood Vessels Stopped by the Mineral Blocks of Bone Substitutes Can Be Avoided by Using Innovative Combined Therapeutics

Biomedicines ◽

10.3390/biomedicines9080952 ◽

2021 ◽

Vol 9 (8) ◽

pp. 952

Author(s):

Fabien Bornert ◽

François Clauss ◽

Guoqiang Hua ◽

Ysia Idoux-Gillet ◽

Laetitia Keller ◽

...

Keyword(s):

Regenerative Medicine ◽

Bone Formation ◽

Medicinal Product ◽

Blood Vessels ◽

Bone Substitute ◽

Bone Substitutes ◽

Bone Defects ◽

New Bone Formation ◽

Polymeric Component ◽

Bone Filling

One major limitation for the vascularization of bone substitutes used for filling is the presence of mineral blocks. The newly-formed blood vessels are stopped or have to circumvent the mineral blocks, resulting in inefficient delivery of oxygen and nutrients to the implant. This leads to necrosis within the implant and to poor engraftment of the bone substitute. The aim of the present study is to provide a bone substitute currently used in the clinic with suitably guided vascularization properties. This therapeutic hybrid bone filling, containing a mineral and a polymeric component, is fortified with pro-angiogenic smart nano-therapeutics that allow the release of angiogenic molecules. Our data showed that the improved vasculature within the implant promoted new bone formation and that the newly-formed bone swapped the mineral blocks of the bone substitutes much more efficiently than in non-functionalized bone substitutes. Therefore, we demonstrated that our therapeutic bone substitute is an advanced therapeutical medicinal product, with great potential to recuperate and guide vascularization that is stopped by mineral blocks, and can improve the regeneration of critical-sized bone defects. We have also elucidated the mechanism to understand how the newly-formed vessels can no longer encounter mineral blocks and pursue their course of vasculature, giving our advanced therapeutical bone filling great potential to be used in many applications, by combining filling and nano-regenerative medicine that currently fall short because of problems related to the lack of oxygen and nutrients.

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A novel methodology for imaging new bone formation around bioceramic bone substitutes

Journal of Biomedical Materials Research Part A ◽

10.1002/jbm.a.31071 ◽

2007 ◽

Vol 81A (2) ◽

pp. 443-445 ◽

Cited By ~ 8

Author(s):

Alejandro A. Gorustovich ◽

Matías G. Sivak ◽

María B. Guglielmotti

Keyword(s):

Bone Formation ◽

Bone Substitutes ◽

New Bone Formation

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The use of solvent-preserved human and bovine cancellous bone blocks for lateral defect augmentation - an experimental controlled study in vivo

Head & Face Medicine ◽

10.1186/s13005-021-00275-1 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Lara Schorn ◽

Tim Fienitz ◽

Kathrin Berndsen ◽

Norbert R. Kübler ◽

Henrik Holtmann ◽

...

Keyword(s):

Bone Formation ◽

Cancellous Bone ◽

Bone Substitute ◽

Bone Matrix ◽

Human Bone ◽

Controlled Study ◽

Bovine Bone ◽

New Bone Formation ◽

Bone Substitute Material ◽

Substitute Material

Abstract Background The aim of this study was to compare new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material in laterally augmented alveolar bone defects using allogeneic, pre-treated and cleaned human bone blocks (tested in dogs, therefore considered to be xenogeneic), and pre-treated and cleaned bovine cancellous bone blocks, both with and without a collagen membrane in order to evaluate their augmentative potential. Methods Thirty-two critical size horizontal defects were prepared in the mandible of 4 adult foxhound dogs (8 per dog, 4 on each side). After 3 months of healing, the defects were laterally augmented in a split-mouth-design with either human (HXB) or bovine solvent-preserved bone blocks (BXB). Afterwards, defects were randomly covered with a bovine collagenous membrane (HXB + M, BXB + M). After a healing interval of 6 months, percentages of new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material were compared. Results Results showed little new bone formation of up to 3.7 % in human bone blocks (HXB 3.7 % ± 10.2, HXB + M 0.3 %± 0.4, BXB, 0.1 % ± 0.8, BXB + M 2.6 % ± 3.2, p = > 0.05). Percentages of fibrous encapsulation were higher in human bone blocks than in bovine bone blocks (HXB 71.2 % ± 8.6, HXB + M 73.71 % ± 10.6, BXB, 60.5 % ± 27.4, BXB + M 52.5 % ± 28.4, p = > 0.05). Resorption rates differed from 44.8 % in bovine bone blocks covered with a membrane to 17.4 % in human bone blocks (HXB 17.4 % ± 7.4, HXB + M 25.9 % ± 10.7, BXB, 38.4 % ± 27.2, BXB + M 44.8 % ± 29.6, p = > 0.05). The use of additional membranes did not significantly affect results. Conclusions Within its limitations, results of this study suggest that solvent-preserved xenogenic human and bovine bone blocks are not suitable for lateral bone augmentation in dogs. Furthermore, defect coverage with a membrane does not positively affect the outcome.

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Physical and Histological Comparison of Hydroxyapatite, Carbonate Apatite, and β-Tricalcium Phosphate Bone Substitutes

Materials ◽

10.3390/ma11101993 ◽

2018 ◽

Vol 11 (10) ◽

pp. 1993 ◽

Cited By ~ 20

Author(s):

Kunio Ishikawa ◽

Youji Miyamoto ◽

Akira Tsuchiya ◽

Koichiro Hayashi ◽

Kanji Tsuru ◽

...

Keyword(s):

Bone Formation ◽

Bone Defect ◽

Tricalcium Phosphate ◽

Bone Substitutes ◽

Physiological Solution ◽

Tissue Response ◽

Histological Evaluation ◽

Carbonate Apatite ◽

Artificial Bone ◽

New Bone Formation

Three commercially available artificial bone substitutes with different compositions, hydroxyapatite (HAp; Neobone®), carbonate apatite (CO3Ap; Cytrans®), and β-tricalcium phosphate (β-TCP; Cerasorb®), were compared with respect to their physical properties and tissue response to bone, using hybrid dogs. Both Neobone® (HAp) and Cerasorb® (β-TCP) were porous, whereas Cytrans® (CO3Ap) was dense. Crystallite size and specific surface area (SSA) of Neobone® (HAp), Cytrans® (CO3Ap), and Cerasorb® (β-TCP) were 75.4 ± 0.9 nm, 30.8 ± 0.8 nm, and 78.5 ± 7.5 nm, and 0.06 m2/g, 18.2 m2/g, and 1.0 m2/g, respectively. These values are consistent with the fact that both Neobone® (HAp) and Cerasorb® (β-TCP) are sintered ceramics, whereas Cytrans® (CO3Ap) is fabricated in aqueous solution. Dissolution in pH 5.3 solution mimicking Howship’s lacunae was fastest in CO3Ap (Cytrans®), whereas dissolution in pH 7.3 physiological solution was fastest in β-TCP (Cerasorb®). These results indicated that CO3Ap is stable under physiological conditions and is resorbed at Howship’s lacunae. Histological evaluation using hybrid dog mandible bone defect model revealed that new bone was formed from existing bone to the center of the bone defect when reconstructed with CO3Ap (Cytrans®) at week 4. The amount of bone increased at week 12, and resorption of the CO3Ap (Cytrans®) was confirmed. β-TCP (Cerasorb®) showed limited bone formation at week 4. However, a larger amount of bone was observed at week 12. Among these three bone substitutes, CO3Ap (Cytrans®) demonstrated the highest level of new bone formation. These results indicate the possibility that bone substitutes with compositions similar to that of bone may have properties similar to those of bone.

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