Integration of Epigallocatechin Gallate in Gelatin Sponges Attenuates Matrix Metalloproteinase-Dependent Degradation and Increases Bone Formation

Matrix metalloproteinase (MMP)-2 and MMP-9 are well-known gelatinases that disrupt the extracellular matrix, including gelatin. However, the advantages of modulating MMP expression in gelatin-based materials for applications in bone regenerative medicine have not been fully clarified. In this study, we examined the effects of epigallocatechin gallate (EGCG), a major polyphenol catechin isolated from green tea, on MMP expression in gelatin sponges and its association with bone formation. Four gelatin sponges with or without EGCG were prepared and implanted into bone defects for up to 4 weeks. Histological and immunohistological staining were performed. Micro-computed tomography was used to estimate the bone-forming capacity of each sponge. Our results showed that EGCG integration attenuated MMP-2 (70.6%) and -9 expression (69.1%) in the 1 week group, increased residual gelatin (118.7%), and augmented bone formation (101.8%) in the 4 weeks group in critical-sized bone defects of rat calvaria compared with vacuum-heated gelatin sponges without EGCG. Moreover, vacuum-heated gelatin sponges with EGCG showed superior bone formation compared with other sponges. The results indicated that integration of EGCG in gelatin-based materials modulated the production and activity of MMP-2 and -9 in vivo, thereby enhancing bone-forming capacity.

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Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

Scientific Reports ◽

10.1038/srep10238 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 16

Author(s):

Philipp S. Lienemann ◽

Stéphanie Metzger ◽

Anna-Sofia Kiveliö ◽

Alain Blanc ◽

Panagiota Papageorgiou ◽

...

Keyword(s):

Computed Tomography ◽

High Resolution ◽

Bone Formation ◽

Bone Regeneration ◽

Bone Defects ◽

Histological Evaluation ◽

Biological Processes ◽

Micro Ct ◽

Pinhole Spect

Abstract Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

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Quantification of bone formation and resorption rates by in vivo micro-computed tomography

Bone ◽

10.1016/j.bone.2009.03.112 ◽

2009 ◽

Vol 44 ◽

pp. S245 ◽

Cited By ~ 4

Author(s):

F.A. Gerhard⁎ ◽

F.M. Lambers ◽

G. Kuhn ◽

R. Muller

Keyword(s):

Computed Tomography ◽

Bone Formation ◽

Micro Computed Tomography

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Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography

PLoS ONE ◽

10.1371/journal.pone.0184835 ◽

2017 ◽

Vol 12 (9) ◽

pp. e0184835 ◽

Cited By ~ 10

Author(s):

Zihui Li ◽

Gisela Kuhn ◽

Michael Schirmer ◽

Ralph Müller ◽

Davide Ruffoni

Keyword(s):

Computed Tomography ◽

Bone Formation ◽

Micro Computed Tomography ◽

Ovariectomized Mice ◽

Implant Integration

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In vivo micro-computed tomography allows direct three-dimensional quantification of both bone formation and bone resorption parameters using time-lapsed imaging

Bone ◽

10.1016/j.bone.2010.10.007 ◽

2011 ◽

Vol 48 (3) ◽

pp. 433-442 ◽

Cited By ~ 122

Author(s):

Friederike A. Schulte ◽

Floor M. Lambers ◽

Gisela Kuhn ◽

Ralph Müller

Keyword(s):

Computed Tomography ◽

Bone Resorption ◽

Bone Formation ◽

Three Dimensional ◽

Micro Computed Tomography

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Bone formation around two titanium implant surfaces placed in bone defects with and without a bone substitute material: A histological, histomorphometric, and micro‐computed tomography evaluation

Clinical Implant Dentistry and Related Research ◽

10.1111/cid.12880 ◽

2020 ◽

Vol 22 (2) ◽

pp. 177-185

Author(s):

Guilherme Trento ◽

Pedro Henrique Carvalho ◽

Erik N. R. Reis ◽

Rubens Spin‐Neto ◽

Ana Paula F. Bassi ◽

...

Keyword(s):

Computed Tomography ◽

Bone Formation ◽

Bone Substitute ◽

Titanium Implant ◽

Bone Defects ◽

Micro Computed Tomography ◽

Bone Substitute Material ◽

Substitute Material

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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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3D-printed Poly-Lactic Co-Glycolic Acid (PLGA) scaffolds in non-critical bone defects impede bone regeneration in rabbit tibia bone

Bio-Medical Materials and Engineering ◽

10.3233/bme-216017 ◽

2021 ◽

pp. 1-7

Author(s):

Jin Xi Lim ◽

Min He ◽

Alphonsus Khin Sze Chong

Keyword(s):

Computed Tomography ◽

Bone Regeneration ◽

Bone Defect ◽

Volume Ratio ◽

Bone Defects ◽

Control Group ◽

Micro Computed Tomography ◽

Rabbit Tibia ◽

3D Printed ◽

Critical Bone Defects

BACKGROUND: An increasing number of bone graft materials are commercially available and vary in their composition, mechanism of action, costs, and indications. OBJECTIVE: A commercially available PLGA scaffold produced using 3D printing technology has been used to promote the preservation of the alveolar socket after tooth extraction. We examined its influence on bone regeneration in long bones of New Zealand White rabbits. METHODS: 5.0-mm-diameter circular defects were created on the tibia bones of eight rabbits. Two groups were studied: (1) control group, in which the bone defects were left empty; (2) scaffold group, in which the PLGA scaffolds were implanted into the bone defect. Radiography was performed every two weeks postoperatively. After sacrifice, bone specimens were isolated and examined by micro-computed tomography and histology. RESULTS: Scaffolds were not degraded by eight weeks after surgery. Micro-computed tomography and histology showed that in the region of bone defects that was occupied by scaffolds, bone regeneration was compromised and the total bone volume/total volume ratio (BV/TV) was significantly lower. CONCLUSION: The implantation of this scaffold impedes bone regeneration in a non-critical bone defect. Implantation of bone scaffolds, if unnecessary, lead to a slower rate of fracture healing.

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Biocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate Nanocomposites in Sheep

The Open Orthopaedics Journal ◽

10.2174/1874325001105010063 ◽

2011 ◽

Vol 5 (1) ◽

pp. 63-71 ◽

Cited By ~ 35

Author(s):

Oliver D Schneider ◽

Dirk Mohn ◽

Roland Fuhrer ◽

Karina Klein ◽

Käthi Kämpf ◽

...

Keyword(s):

Calcium Phosphate ◽

Bone Formation ◽

Antimicrobial Properties ◽

Drill Hole ◽

Bone Defects ◽

Long Bone ◽

Minimal Amount ◽

Cotton Wool

Background: The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. Materials and Methods: Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. Results: Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. Conclusions: The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects.

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