Marrow-derived Progenitor Cell Injections Enhance New Bone Formation during Distraction

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.

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Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-03971-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Hideki Ueyama ◽

Yoichi Ohta ◽

Yuuki Imai ◽

Akinobu Suzuki ◽

Ryo Sugama ◽

...

Keyword(s):

Bone Marrow ◽

Bone Formation ◽

Bone Structure ◽

Precursor Cells ◽

The Other ◽

Bone Morphogenetic Protein 2 ◽

New Bone Formation ◽

Micro Computed Tomography ◽

Mineral Density ◽

Left Femur

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

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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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Maxillary Sinus Augmentation Using Ceramic Alloplastic Granules or Paste: An Experimental Study in Rabbits

Dentistry Journal ◽

10.3390/dj9060065 ◽

2021 ◽

Vol 9 (6) ◽

pp. 65

Author(s):

Michael Medeiros Costa ◽

Daniele Botticelli ◽

Ofer Moses ◽

Yuki Omori ◽

Shigeo Fujiwara ◽

...

Keyword(s):

Bone Formation ◽

Maxillary Sinus ◽

Biological Behavior ◽

Collagen Membrane ◽

Alloplastic Material ◽

New Bone Formation ◽

Sinus Augmentation ◽

Beta Tricalcium Phosphate ◽

Sinus Lifting ◽

Points Of View

Background: Due to the lack of data comparing the biological behavior of two formulations, granules and paste, of alloplastic graft from microtomographic and histomorphometric points of view, the aim of the present experiment was to compare the histomorphometric and microtomographic healing of two formulations, i.e., granules (MR sites) or paste (MR-inject sites) of an alloplastic graft composed of a combination of beta-tricalcium phosphate and hydroxyapatite used for maxillary sinus lifting. Methods: A sinus lifting procedure was carried out bilaterally in 20 rabbits, and the elevated space was filled with either paste or granules of an alloplastic material. A collagen membrane was placed on the antrostomy and the animals were euthanized after 2 or 10 weeks, 10 animals each group. Microtomographic and histological analyses were performed. Results: Higher proportions of new bone formation were found at the MR, compared to the MR-inject sites both after 2 weeks (2.65 ± 2.89% vs. 0.08 ± 0.12%; p < 0.01) and 10 weeks of healing (34.20 ± 13.86 vs. 23.28 ± 10.35%; p = 0.022). Conclusions: It was concluded that new bone formation was faster in the MR sites, compared to the MR-inject. However, a longer time of healing should be allowed to make final conclusions about the efficiency in bone formation of the paste formulation of the biomaterial used in the present study.

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