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

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.

scholarly journals Micro-Computed Tomography Analysis of Subchondral Bone Regeneration Using Osteochondral Scaffolds in an Ovine Condyle Model

2021 ◽  
Vol 11 (3) ◽  
pp. 891
Author(s):  
Taylor Flaherty ◽  
Maryam Tamaddon ◽  
Chaozong Liu
Keyword(s):  
Computed Tomography ◽  
Bone Regeneration ◽  
Subchondral Bone ◽  
Volume Ratio ◽  
Bone Volume ◽  
Osteochondral Defects ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Trabecular Thickness ◽  
Osteochondral Scaffold

Osteochondral scaffold technology has emerged as a promising therapy for repairing osteochondral defects. Recent research suggests that seeding osteochondral scaffolds with bone marrow concentrate (BMC) may enhance tissue regeneration. To examine this hypothesis, this study examined subchondral bone regeneration in scaffolds with and without BMC. Ovine stifle condyle models were used for the in vivo study. Two scaffold systems (8 mm diameter and 10 mm thick) with and without BMC were implanted into the femoral condyle, and the tissues were retrieved after six months. The retrieved femoral condyles (with scaffold in) were examined using micro-computed tomography scans (micro-CT), and the micro-CT data were further analysed by ImageJ with respect to trabecular thickness, bone volume to total volume ratio (BV/TV) ratio, and degree of anisotropy of bone. Statistical analysis compared bone regeneration between scaffold groups and sub-set regions. These results were mostly insignificant (p < 0.05), with the exception of bone volume to total volume ratio when comparing scaffold composition and sub-set region. Additional trends in the data were observed. These results suggest that the scaffold composition and addition of BMC did not significantly affect bone regeneration in osteochondral defects after six months. However, this research provides data which may guide the development of future treatments.

scholarly journals Evaluation of a poly(lactic-acid) scaffold filled with poly(lactide-co-glycolide)/hydroxyapatite nanofibres for reconstruction of a segmental bone defect in a canine model

2019 ◽  
Vol 64 (No. 12) ◽  
pp. 531-538
Author(s):  
JW Yun ◽  
SY Heo ◽  
MH Lee ◽  
HB Lee
Keyword(s):  
Lactic Acid ◽  
Bone Defect ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Poly Lactic Acid ◽  
Micro Computed Tomography ◽  
Bone Parameters ◽  
3D Printed ◽  
Group 3 ◽  
Group 2

Critical-sized bone defects are a difficult problem in both human and veterinary medicine. To address this issue, synthetic graft materials have been garnering attention. Abundant in vitro studies have proven the possibilities of poly(lactic-acid) (PLA) scaffolds and poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HAp) nanofibres for treating bone defects. The present study aimed at conducting an in vivo assessment of the biological performance of a three dimensional (3D)-printed PLA scaffold filled with a PLGA/HAp nanofibrous scaffold to estimate its potential applications in bone defect reconstruction surgery. Defects were created in a 20 mm-long region of the radius bone. The defects created on the right side in six Beagle dogs (n = 6) were left untreated (Group 1). The defects on the left side (n = 6) were filled with 3D-printed PLA scaffolds incorporated with PLGA/Hap nanofibres with gelatine (Group 2). The other six Beagle dog defects were made bilaterally (n = 12) and filled with the same material as that used in Group 2 along with recombinant bone morphogenetic protein 2 (rhBMP-2) (Group 3). Both the radiological and histological examinations were performed for observing the reaction of the scaffold and the bone. Micro-computed tomography (CT) was utilised for the evaluation of the bone parameters 20 weeks after the experiment. The radiological and histological results revealed that the scaffold was biodegradable and was replaced by new bone tissue. The micro-CT revealed that the bone parameters were significantly (P &lt; 0.05) increased in Group 3. Based on these results, our study serves as a foundation for future studies on bone defect treatment using synthetic polymeric scaffolds.

scholarly journals The Development of Gelatin/Hyaluronate Copolymer Mixed with Calcium Sulfate, Hydroxyapatite, and Stromal-Cell-Derived Factor-1 for Bone Regeneration Enhancement

Polymers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1454 ◽  
Author(s):  
Yun-Liang Chang ◽  
Chia-Ying Hsieh ◽  
Chao-Yuan Yeh ◽  
Feng-Huei Lin
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Calcium Sulfate ◽  
Stromal Cell ◽  
Femoral Condyle ◽  
Bone Defects ◽  
Blood Analysis ◽  
Control Group ◽  
Defect Model ◽  
Stromal Cell Derived Factor

In clinical practice, bone defects still remain a challenge. In recent years, apart from the osteoconductivity that most bone void fillers already provide, osteoinductivity has also been emphasized to promote bone healing. Stromal-cell-derived factor-1 (SDF-1) has been shown to have the ability to recruit mesenchymal stem cells (MSCs), which play an important role in the bone regeneration process. In this study, we developed a gelatin–hyaluronate (Gel-HA) copolymer mixed with calcium sulfate (CS), hydroxyapatite (HAP), and SDF-1 in order to enhance bone regeneration in a bone defect model. The composites were tested in vitro for biocompatibility and their ability to recruit MSCs after material characterization. For the in vivo test, a rat femoral condyle bone defect model was used. Micro computed tomography (Micro-CT), two-photon excitation microscopy, and histology analysis were performed to assess bone regeneration. As expected, enhanced bone regeneration was well observed in the group filled with Gel-HA/CS/HAP/SDF-1 composites compared with the control group in our animal model. Furthermore, detailed blood analysis of rats showed no obvious systemic toxicity or side effects after material implantation. In conclusion, the Gel-HA/CS/HAP/SDF-1 composite may be a safe and applicable material to enhance bone regeneration in bone defects.

scholarly journals Fabrication of Stromal Cell-Derived Factor-1 Contained in Gelatin/Hyaluronate Copo006Cymer Mixed with Hydroxyapatite for Use in Traumatic Bone Defects

Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 822
Author(s):  
Yun-Liang Chang ◽  
Chia-Ying Hsieh ◽  
Chao-Yuan Yeh ◽  
Chih-Hao Chang ◽  
Feng-Huei Lin
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Stromal Cell ◽  
Second Harmonic ◽  
Bone Defects ◽  
In Vivo Studies ◽  
Control Group ◽  
Defect Model ◽  
Stromal Cell Derived Factor ◽  
Bone Void

Bone defects of orthopedic trauma remain a challenge in clinical practice. Regarding bone void fillers, besides the well-known osteoconductivity of most bone substitutes, osteoinductivity has also been gaining attention in recent years. It is known that stromal cell-derived factor-1 (SDF-1) can recruit mesenchymal stem cells (MSCs) in certain circumstances, which may also play an important role in bone regeneration. In this study, we fabricated a gelatin/hyaluronate (Gel/HA) copolymer mixed with hydroxyapatite (HAP) and SDF-1 to try and enhance bone regeneration in a bone defect model. After material characterization, these Gel/HA–HAP and Gel/HA–HAP–SDF-1 composites were tested for their biocompatibility and ability to recruit MSCs in vitro. A femoral condyle bone defect model of rats was used for in vivo studies. For the assessment of bone healing, micro-CT analysis, second harmonic generation (SHG) imaging, and histology studies were performed. As a result, the Gel/HA–HAP composites showed no systemic toxicity to rats. Gel/HA–HAP composite groups both showed better bone generation compared with the control group in an animal study, and the composite with the SDF-1 group even showed a trend of faster bone growth compared with the composite without SDF-1 group. In conclusion, in the management of traumatic bone defects, Gel/HA–HAP–SDF-1 composites can be a feasible material for use as bone void fillers.

scholarly journals Doxycycline and Zinc Loaded Silica-Nanofibrous Polymers as Biomaterials for Bone Regeneration

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1201 ◽  
Author(s):  
Manuel Toledano ◽  
Manuel Toledano-Osorio ◽  
Raquel Osorio ◽  
Álvaro Carrasco-Carmona ◽  
José-Luis Gutiérrez-Pérez ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Repair ◽  
Sio2 Nanoparticles ◽  
Bone Architecture ◽  
Control Group ◽  
M2 Macrophages ◽  
Micro Computed Tomography ◽  
Nanostructured Membranes ◽  
Critical Bone Defects ◽  
And Control

The main target of bone tissue engineering is to design biomaterials that support bone regeneration and vascularization. Nanostructured membranes of (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 loaded with 5% wt of SiO2-nanoparticles (HOOC-Si-Membrane) were doped with zinc (Zn-HOOC-Si-Membrane) or doxycycline (Dox-HOOC-Si-Membrane). Critical bone defects were effectuated on six New Zealand-bred rabbit skulls and covered with the membranes. After six weeks, the bone architecture was evaluated with micro computed tomography. Three histological analyses were utilized to analyse bone regeneration, including von Kossa silver nitrate, toluidine blue and fluorescence. All membrane-treated defects exhibited higher number of osteocytes and bone perimeter than the control group without the membrane. Zn-HOOC-Si-Membranes induced higher new bone and osteoid area than those treated with HOOC-Si-Membranes, and control group, respectively. Zn-HOOC-Si-Membranes and Dox-HOOC-Si-Membranes attained the lowest ratio M1 macrophages/M2 macrophages. Dox-HOOC-Si-Membranes caused the lowest number of osteoclasts, and bone density. At the trabecular new bone, Zn-HOOC-Si-Membranes produced the highest angiogenesis, bone thickness, connectivity, junctions and branches. Zn-HOOC-Si-Membranes enhanced biological activity, attained a balanced remodeling, and achieved the greatest regenerative efficiency after osteogenesis and angiogenesis assessments. The bone-integrated Zn-HOOC-Si-Membranes can be considered as bioactive modulators provoking a M2 macrophages (pro-healing cells) increase, being a potential biomaterial for promoting bone repair.

scholarly journals Polydopamine functionalized VEGF gene-activated 3D printed scaffolds for bone regeneration

RSC Advances ◽  
2021 ◽  
Vol 11 (22) ◽  
pp. 13282-13291
Author(s):  
Jaidev L. Chakka ◽  
Timothy Acri ◽  
Noah Z. Laird ◽  
Ling Zhong ◽  
Kyungsup Shin ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Blood Vessels ◽  
Bone Defects ◽  
Vegf Gene ◽  
3D Printed ◽  
Critical Bone Defects

Bone is a highly vascularized organ and the formation of new blood vessels is essential to regenerate large critical bone defects.

scholarly journals Analysis of the behavior of a biomaterial based on wollastonite/TCP in the implant process of an experimental model of critical bone defects

2021 ◽  
Vol 10 (7) ◽  
pp. e55110716800
Author(s):  
Mauricio Mitsuo Monção ◽  
Raísa Cavalcante Dourado ◽  
Luísa Queiroz Vasconcelos ◽  
Isabela Cerqueira Barreto ◽  
Roberto Paulo Correia de Araújo
Keyword(s):  
Experimental Model ◽  
Bone Defect ◽  
Blood Clot ◽  
Study Groups ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Control Group ◽  
Hydrophilic Behavior ◽  
Critical Bone Defects

This study analyzes the clinical, macroscopic and radiographic characteristics of a biomaterial with different proportions of wolastonite (W) and tricalcium phosphate (TCP) on bone tissue regeneration during the implantation process of an experimental model of critical bone defects. Fifteen Wistar rats were used, randomly distributed in 5 groups (n = 3), with a bone defect created on an 8.0 mm diameter calvaria. 4 groups received implants with different proportions of W%/TCP%, referred to as W20/TCP80, W40/TCP60, W60/TCP40 and W80/TCP20. The fifth control group (GC) was filled with blood clot only. Clinical evaluation was performed every 24 hours, and after 7 days, the animals were euthanized. The calvaria were dissected and analyzed macroscopically and by radiography. All study groups showed a satisfactory clinical evolution. The macroscopic analysis showed filling of the bone defect with granules surrounded by newly formed tissue, and the radiographic analysis showed different patterns of displacement of the biomaterial. The study concluded that the different proportions of W%/TCP% were well tolerated by the study groups and demonstrated biocompatibility. The enhanced hydrophilic behavior of the W40/TCP60, W60/TCP40 and W80/TCP20 groups favored the application in the experimental model in vivo.

scholarly journals Effect of CD146 on Bone Regeneration by Transplantation of Stem Cells from Human Exfoliated Deciduous Teeth into Mouse Skull Defect

2021 ◽  
Author(s):  
Kodai Rikitake ◽  
Ryo Kunimatsu ◽  
Yuki Yoshimi ◽  
Kengo Nakajima ◽  
Tomoka Hiraki ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Stem Cells ◽  
Bone Regeneration ◽  
Bone Defects ◽  
Deciduous Teeth ◽  
Regeneration Ability ◽  
Micro Computed Tomography ◽  
Heterogeneous Populations ◽  
Immunodeficient Mice ◽  
Human Exfoliated Deciduous Teeth

Abstract Stem cells from human exfoliated deciduous teeth (SHED) possess bone regeneration ability and may have therapeutic applications. CD146, a cell adhesion protein expressed by vascular endothelial cells, is involved in the osteoblastic differentiation of stem cells. However, the effect of CD146 on SHED-mediated bone regeneration in vivo remains unknown. Hence, in this study we aimed to establish efficient conditions for SHED transplantation. SHED were isolated from the pulp of an extracted deciduous tooth and cultured, and CD146-positive (CD146+) and CD146-negative (CD146−) populations were sorted. Heterogeneous populations of SHED and CD146+ and CD146– cells were transplanted into bone defects generated in the skulls of individual immunodeficient mice. Micro-computed tomography was performed immediately post-transplantation and at 4- and 8-weeks thereafter to evaluate bone regeneration. Histological and immunohistochemical assessments were also performed at 8 weeks after transplantation. Micro-computed tomography revealed bone regeneration upon transplantation with CD146+ and heterogeneous populations of SHED, particularly at 8 weeks after transplantation, with significantly higher bone regeneration observed following transplantation with CD146+ cells. Furthermore, histological and immunohistochemical assessments revealed that CD146+ cells promoted bone regeneration and angiogenesis. Therefore, transplantation of CD146+ SHED into bone defects may serve as a useful strategy for bone regeneration.

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

2015 ◽  
Vol 5 (1) ◽  
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.

scholarly journals Repair of critical-size porcine craniofacial bone defects using a collagen-polycaprolactone composite biomaterial

2021 ◽  
Author(s):  
Marley J Dewey ◽  
Derek J Milner ◽  
Daniel Weisgerber ◽  
Colleen Flanagan ◽  
Marcello Rubessa ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Fibrous Tissue ◽  
Bone Defects ◽  
Large Animal ◽  
Collagen Scaffolds ◽  
Shape Fitting ◽  
Large Animal Models ◽  
3D Printed ◽  
Mineralized Collagen

Regenerative medicine approaches for massive craniomaxillofacial bone defects face challenges associated with the scale of missing bone, the need for rapid graft-defect integration, and challenges related to inflammation and infection. Mineralized collagen scaffolds have been shown to promote mesenchymal stem cell osteogenesis due to their porous nature and material properties, but are mechanically weak, limiting surgical practicality. Previously, these scaffolds were combined with 3D-printed polycaprolactone mesh to form a scaffold-mesh composite to increase strength and promote bone formation in sub-critical sized porcine ramus defects. Here, we compare the performance of mineralized collagen-polycaprolactone composites to the polycaprolactone mesh in a critical-sized porcine ramus defect model. While there were no differences in overall healing response between groups, our data demonstrated broadly variable metrics of healing regarding new bone infiltration and fibrous tissue formation. Abscesses were present surrounding some implants and polycaprolactone polymer was still present after 9-10 months of implantation. Overall, while there was limited successful healing, with 2 of 22 implants showed substantial levels of bone regeneration, and others demonstrating some form of new bone formation, the results suggest targeted improvements to improve repair of large animal models to more accurately represent craniomaxillofacial bone healing. Notably, strategies to increase osteogenesis throughout the implant, modulate the immune system to support repair, and employ shape-fitting tactics to avoid implant micromotion and resultant fibrosis. Improvements to the mineralized collagen scaffolds involve changes in pore size and shape to increase cell migration and osteogenesis and inclusion or delivery of factors to aid vascular ingrowth and bone regeneration.

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