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

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 952
Author(s):  
Fabien Bornert ◽  
François Clauss ◽  
Guoqiang Hua ◽  
Ysia Idoux-Gillet ◽  
Laetitia Keller ◽  
...  

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.

2020 ◽  
Vol 8 (1) ◽  
pp. 7 ◽  
Author(s):  
Savvas Titsinides ◽  
Theodore Karatzas ◽  
Despoina Perrea ◽  
Efstathios Eleftheriadis ◽  
Leonidas Podaropoulos ◽  
...  

Regeneration of large jaw bone defects still remains a clinical challenge. To avoid incomplete bone repair, bone grafts have been advocated to support the healing process. This study comparatively evaluated new bone formation among a synthetic graft substitute, a human bone derivative, and a bovine xenograft. Materials were placed in 3 out of the 4 bone cavities, while 1 deficit was left empty, serving as a control, in mono-cortical defects, surgically prepared in the porcine calvaria bone. Animals were randomized in 2 groups and euthanized at 8 and 12 weeks. Harvested tissue specimens were qualitatively evaluated by histology. New bone formation was quantitatively measured by histomorphometry. Maximum new bone formation was noticed in defects grafted with beta-tricalcium phosphate b-TCP compared to the other bone substitutes, at 8 and 12 weeks post-surgery. Bovine and human allograft induced less new bone formation compared to empty bone cavity. Histologic analysis revealed that b-TCP was absorbed and substituted significantly, while bovine and human allograft was maintained almost intact in close proximity with new bone. Based on our findings, higher new bone formation was detected in defects filled with b-TCP when compared to bovine and human graft substitutes.


2006 ◽  
Vol 309-311 ◽  
pp. 255-258
Author(s):  
Y.S. Kim ◽  
Tae Gyun Kim ◽  
Ui Won Jung ◽  
C.S. Kim ◽  
Seong Ho Choi ◽  
...  

Dehiscence bone defects, frequently observed on dental implants placed in periodontitis-affected alveolar bone or extraction sockets were treated with β-tricalcium phosphate (β –TCP) and chitosan membrane for guided bone regeneration, and the new bone formation on the treated sites were studied. Beagle dogs were used for the experiment. First to fourth mandibular premolars were extracted, and the post extraction alveolar bone surface was planed. After 8 weeks of healing, 3 by 4mm dehiscence defects were created using straight fissure burs. Total of 16 oxidized titanium surface implants were placed on the bone defects of the subjects, two on each side. Control sites were treated with implants only. Experimental Group 1 sites were treated with implants and chitosan membrane. Experimental Group 2 sites were treated with implants, β-TCP and chitosan membrane. Experimental Group 3 sites were treated with implants, β-TCP, autogenous bone and chitosan membrane. The animals were sacrificed 12 weeks after implant placement, and the specimens from the treated sites were histologically studied with following results. Limited amount of new bone formation was observed in control group with unexposed membrane. Slightly greater amount of bone formation was observed on sites treated with β-TCP+membrane or autogenous bone+ β-TCP+membrane compared to control group. Remnants of chitosan membrane and β-TCP encapsulated with connective tissue were observed during experimental periods. These results suggest that further studies are needed on membrane rigidity and infection control for space maintenance underneath the membrane and bone substitutes in the treatment of dehiscence defects.


2007 ◽  
Vol 81A (2) ◽  
pp. 443-445 ◽  
Author(s):  
Alejandro A. Gorustovich ◽  
Matías G. Sivak ◽  
María B. Guglielmotti

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Lara Schorn ◽  
Tim Fienitz ◽  
Kathrin Berndsen ◽  
Norbert R. Kübler ◽  
Henrik Holtmann ◽  
...  

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.


Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 1993 ◽  
Author(s):  
Kunio Ishikawa ◽  
Youji Miyamoto ◽  
Akira Tsuchiya ◽  
Koichiro Hayashi ◽  
Kanji Tsuru ◽  
...  

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.


2005 ◽  
Vol 284-286 ◽  
pp. 811-814 ◽  
Author(s):  
Toshiki Itoh ◽  
Seiji Ban ◽  
T. Watanabe ◽  
Shozo Tsuruta ◽  
Takahiro Kawai ◽  
...  

It is well known that bone morphogenetic protein (BMP) induces bone formation and requires for carriers. Poly-lactic acid / poly-glycolic acid (PLGA) is frequently used as the carriers of BMP. We developed a biodegradable composite PLGA membrane, which was containing oriented needle-like apatite with BMP. The composite membranes were implanted into the thigh muscle pouch of 3-week-old-mice. At 3 weeks after implantation, the implanted area was observed by optical microscopy. The composite membrane containing oriented needle-like apatite with BMP induced new bone formation. It seems that this composite membrane might be a scaffold of BMP and promoting the healing of bone defects.


2012 ◽  
Vol 529-530 ◽  
pp. 300-303 ◽  
Author(s):  
R.P. Félix Lanao ◽  
J.W.M. Hoekstra ◽  
Joop G.C. Wolke ◽  
Sander C.G. Leeuwenburgh ◽  
A.S. Plachokova ◽  
...  

Periodontitis is one of the most common inflammatory diseases, which can lead to early tooth loss. The conventional treatment of periodontitis is to arrest the disease progression. Most reconstructive procedures involve application of bone substitutes, barrier membranes or a combination of both into the bony defects. Calcium phosphate cements (CPCs) are the predominant type of bone substitute material used for reasons of injectability and hence perfect filling potential for bone defects. Recently, injectable apatitic CPCs demonstrated to be more rapidly degradable when combined with poly (lactic-co-glycolic) acid (PLGA) microspheres. Further, PLGA microspheres can be used as a delivery vehicle for growth factors. In this study, the performance of injectable CPCs as a bone substitute material for alveolar bone defects created in Beagle dogs was evaluated. Four CPC-formulations were generated by incorporating hollow or dense PLGA microspheres, either or not loaded with the growth factors (platelet derived growth factor (PDGF) and insulin-like growth factor (IGF). Implantation period was 8 weeks. Bone formation was based on histological and histomorphometrical evaluation. The results demonstrated that filling alveolar bone defects with CPC-dense PLGA revealed significant more bone formation compared to CPC-hollow PLGA either or not loaded with IGF and PDGF. In summary, we conclude that injectable CPC-dense PLGA composites proved to be the most suitable material for a potential use as off the shelf material due to its good biocompatibility, enhanced degradability and subsequent bone formation.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ruimin Liu ◽  
Mingdong Yan ◽  
Sulin Chen ◽  
Wenxiu Huang ◽  
Dong Wu ◽  
...  

Purpose. To date, it remains unknown whether the addition of platelet-rich fibrin (PRF) to bone grafts actually improves the effectiveness of maxillary sinus augmentation. This study aimed to perform a meta-analysis to evaluate the efficacy of PRF in sinus lift.Materials and Methods. PubMed, Embase, and the Cochrane Library were searched. Randomized controlled studies were identified. The risk of bias was evaluated using the Cochrane Collaboration tool.Results. Five RCTs were included in our meta-analysis. Clinical, radiographic, and histomorphometric outcomes were considered. No implant failure or graft failure was detected in all included studies within the follow-up period. The percentage of contact length between newly formed bone substitute and bone in the PRF group was lower but lacked statistical significance (3.90%, 95% CI, -2.91% to 10.71%). The percentages of new bone formation (-1.59%, 95% CI, -5.36% to 2.18%) and soft-tissue area (-3.73%, 95% CI, -10.11% to 2.66%) were higher in the PRF group but were not significantly different. The percentage of residual bone graft was not significant in either group (4.57%, 95% CI, 0% to 9.14%).Conclusions. Within the limitations of this review, it was concluded that there were no statistical differences in survival rate, new bone formation, contact between newly formed bone and bone substitute, percentage of residual bone graft (BSV/TV), and soft-tissue area between the non-PRF and PRF groups. Current evidence supporting the necessity of adding PRF to bone graft in sinus augmentation is limited.


2020 ◽  
Vol 9 (11) ◽  
pp. 3764
Author(s):  
Sangyup Kim ◽  
Jong-Hyuk Chung ◽  
Seung-Yun Shin ◽  
Seung-Il Shin ◽  
Ji-Youn Hong ◽  
...  

Schneiderian membrane perforation (SMP) is the most common complication during sinus floor elevation (SFE). Conventional methods to repair SMP, such as using a collagen barrier, may be clinically demanding. The aim of the present study was to compare the effects of collagenated bone substitute materials with and without a collagen barrier to repair SMP during SFE in terms of new bone formation and dimensional stability. In 12 rabbits, intentional SMP was made during bilateral SFE. The rabbits were randomly assigned under two groups: the control group, in which the sinus was repaired with a collagen barrier, and the test group, in which the sinus was repaired without a collagen barrier. Collagenated bone substitute material was grafted in both groups. Healing periods of 2 weeks and 4 weeks were provided in both groups. There were no adverse clinical events. Histology revealed that the Schneiderian membrane had atrophied with loss of cilia and serous glands in both groups at 4 weeks. Histomorphometry revealed that the newly formed bone (test: 0.42 ± 0.17 mm2, control: 0.36 ± 0.18 mm2 at 2 weeks; test: 1.21 ± 0.36 mm2, control: 1.23 ± 0.55 mm2 at 4 weeks) or total augmented area did not significantly differ between the two groups at either time points (p > 0.05). In conclusion, collagenated bone substitute material without a collagen barrier demonstrated similar new bone formation and dimensional stability as that with a collagen barrier in repairing SMP.


1988 ◽  
Vol 69 (2) ◽  
pp. 269-275 ◽  
Author(s):  
Charles E. Rawlings ◽  
Robert H. Wilkins ◽  
Jacob S. Hanker ◽  
Nicholas G. Georgiade ◽  
John M. Harrelson

✓ The materials ordinarily used to reconstruct bone defects in the calvaria and facial bones either are difficult to shape, are partially resorbed by the body, or are likely to become infected if used near a contaminated area such as the frontal sinus. Calcium sulfate hemihydrate (plaster of Paris) has been known for years to have excellent reparative qualities in bone defects, but ordinarily it is quickly resorbed. Consequently, a new material, a composite of a dense form of plaster of Paris and hydroxylapatite, was devised to provide nonabsorbable hydroxylapatite particles for bone to form around and within during the phase of plaster absorption. Two types of this material were evaluated in cranial defects in cats. Each of the plaster of Paris/hydroxylapatite mixtures was placed into a surgically unroofed frontal sinus and into a contralateral parietal trephine hole in a group of 32 cats. Two cats in each group succumbed to anesthesia, leaving two sets of 30 cats. During the entire follow-up period there was only one other death, with no evidence of wound infection, wound dehiscence, implant rejection, or cerebral dysfunction among the survivors. The cats in each group were sacrificed at 1, 2, 3, 5, 7, 8, 9, 10, or 12 months after operation. Following sacrifice, both the frontal and parietal defects were exposed and examined visually, histologically, and with histomorphometric analysis for new bone formation. New bone formation was present as early as 1 month after operation and continued to increase during the 12 months of the study. Based upon these osteogenic qualities, the ease of shaping the composite, and the lack of infection in the frontal sinus region, it is concluded that this substance could be a valuable new material for human cranioplasty.


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