Osteoinductive 3D Printed Scaffold Healed 5 cm Segmental Bone Defects in the Ovine Metatarsus

Abstract Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in the sheep metatarsus. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

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Osteoinductive 3D printed scaffold healed 5 cm segmental bone defects in the ovine metatarsus

Scientific Reports ◽

10.1038/s41598-021-86210-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yunzhi Peter Yang ◽

Kevin M. Labus ◽

Benjamin C. Gadomski ◽

Arnaud Bruyas ◽

Jeremiah Easley ◽

...

Keyword(s):

Bone Regeneration ◽

Large Scale ◽

Composite Scaffold ◽

Bone Grafts ◽

Bone Defects ◽

Collagen Sponge ◽

Bone Morphogenetic Protein 2 ◽

3D Printed ◽

Autologous Bone ◽

Autologous Bone Grafts

AbstractAutologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

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Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs

Injury ◽

10.1016/j.injury.2009.12.005 ◽

2010 ◽

Vol 41 (7) ◽

pp. 717-723 ◽

Cited By ~ 44

Author(s):

M. Hakimi ◽

P. Jungbluth ◽

M. Sager ◽

M. Betsch ◽

M. Herten ◽

...

Keyword(s):

Platelet Rich Plasma ◽

Bone Grafts ◽

Bone Defects ◽

Long Bone ◽

Combined Use ◽

Autologous Bone ◽

Autologous Bone Grafts ◽

Mini Pigs

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Hydrogels that allow and facilitate bone repair, remodeling, and regeneration

Journal of Materials Chemistry B ◽

10.1039/c5tb01043h ◽

2015 ◽

Vol 3 (40) ◽

pp. 7818-7830 ◽

Cited By ~ 41

Author(s):

Aaron R. Short ◽

Deepthi Koralla ◽

Ameya Deshmukh ◽

Benjamin Wissel ◽

Benjamin Stocker ◽

...

Keyword(s):

Gold Standard ◽

Bone Repair ◽

Standard Treatment ◽

Bone Grafts ◽

Bone Defects ◽

Surgical Reconstruction ◽

Congenital Deformity ◽

Bone Stock ◽

Autologous Bone ◽

Autologous Bone Grafts

Bone defects can originate from a variety of causes, including trauma, cancer, congenital deformity, and surgical reconstruction. Success of the current “gold standard” treatment (i.e., autologous bone grafts) is greatly influenced by insufficient or inappropriate bone stock.

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Bone Morphogenetic Protein-2 Incorporated Beta-Tricalcium Phosphate Enhanced Bone Regeneration of Critical-Sized Bone Defects in Rats

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.782.283 ◽

2018 ◽

Vol 782 ◽

pp. 283-288 ◽

Cited By ~ 1

Author(s):

Ling Fei Wei ◽

Gang Wu ◽

Li Quan Deng ◽

Yue Lian Liu

Keyword(s):

Bone Regeneration ◽

Bone Morphogenetic Protein ◽

Tricalcium Phosphate ◽

Histopathological Examination ◽

Bone Defects ◽

Biological Evaluation ◽

Bone Morphogenetic Protein 2 ◽

Beta Tricalcium Phosphate ◽

Morphogenetic Protein ◽

Autologous Bone

Although preclinical and clinical studies have shown the benefits of bone morphogenetic protein-2 (BMP2) in bone regeneration, there are increasing concerns about its side effects. These are mainly due to the high dosage of BMP2 which is necessary to obtain the desired clinical results. Previously our group has developed a novel controlled-release delivery system; the biomimetic calcium phosphate coating incorporated with BMP2. It can be used at much lower concentrations of BMP2 than those used in the commercially available product and still produce similar biological effects. In this study, we made a primarily biological evaluation of BMP2 incorporated beta-tricalcium phosphate (β-TCP) for bone regeneration in critical-sized bone defects. Critical-sized calvarial defects were created in rats. They were divided into four groups as follows: (1) empty defects (control), (2) defects filled with β-TCP, (3) defects filled with BMP2 incorporated β-TCP, (4) defects filled with autologous bone. Eight weeks after the operation, the efficiency of the materials was evaluated using histology and histomorphometry. Moreover, the safety of the materials was evaluated using routine blood examination, blood biochemistry examination and histopathological examination of viscera. BMP2 incorporated β-TCP demonstrated an efficiency of bone regeneration that was comparable with autologous bone, with the highest levels of new bone formation (38.3±8.4 mm3 versus 30.1±9.9 mm3, p < 0.05). All clinical lab index of blood in these four groups were within the normal range. Moreover, no change related to the treatment was noted in the histopathological examination of viscera. The results from the present study demonstrated that BMP2 incorporated β-TCP could be a promising substitute for autologous bone used for bone regeneration. Future clinical trials and preclinical trials with large animal models are necessary to investigate the safety and efficacy of BMP2 incorporated β-TCP.

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Treatment of Bone Defects Produced by Lower Molar Extraction Using Ultrasound-Harvested Autologous Bone Grafts

Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.joms.2006.09.019 ◽

2008 ◽

Vol 66 (1) ◽

pp. 189-192 ◽

Cited By ~ 2

Author(s):

Miguel Penarrocha ◽

Dolores Gomez ◽

Berta Garcia ◽

Jose Vicente Bagan

Keyword(s):

Bone Grafts ◽

Bone Defects ◽

Autologous Bone ◽

Autologous Bone Grafts ◽

Lower Molar ◽

Molar Extraction

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Inductive biomaterials for bone regeneration

Journal of Materials Research ◽

10.1557/jmr.2017.39 ◽

2017 ◽

Vol 32 (6) ◽

pp. 1047-1060 ◽

Cited By ~ 6

Author(s):

Rafid Kasir ◽

Varadraj N. Vernekar ◽

Cato T. Laurencin

Keyword(s):

Bone Regeneration ◽

Disease Transmission ◽

Bone Growth ◽

Bone Defects ◽

The Other ◽

Risk Of Disease ◽

Autologous Bone ◽

Materials Used ◽

Autologous Bone Grafts ◽

Induce Bone Formation

Inductive biomaterials are sought as alternatives to traditional materials used to treat bone defects. Traditional materials include autologous bone grafts that must be obtained surgically, and allografts that carry the risk of disease transmission and infection. Whereas the use of growth factors to stimulate bone growth has seen considerable advances, their efficacy is usually limited to supra-physiological doses with considerable side effects. On the other hand, certain biomaterials have an intrinsic ability to stimulate bone regeneration in lieu of growth factor use, and their use in repairing bone defects as well as improving the osteointegration of implants has been promising. These materials known as osteoinductive biomaterials include ceramics, metals, polymers, and composites of these materials. In this review, we examine the relevant properties of these different materials in their ability to induce bone formation.

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Autologous bone grafts with MSCs or FGF-2 accelerate bone union in large bone defects

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-016-0442-6 ◽

2016 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Hiroaki Murakami ◽

Tomoyuki Nakasa ◽

Masakazu Ishikawa ◽

Nobuo Adachi ◽

Mitsuo Ochi

Keyword(s):

Bone Grafts ◽

Bone Defects ◽

Bone Union ◽

Autologous Bone ◽

Autologous Bone Grafts ◽

Large Bone ◽

Large Bone Defects

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Does the Use of Laser Photobiomodulation, Bone Morphogenetic Proteins, and Guided Bone Regeneration Improve the Outcome of Autologous Bone Grafts? An in Vivo Study in a Rodent Model

Photomedicine and Laser Surgery ◽

10.1089/pho.2007.2172 ◽

2008 ◽

Vol 26 (4) ◽

pp. 371-377 ◽

Cited By ~ 50

Author(s):

Cristian S. Torres ◽

Jean N. dos Santos ◽

Juliana S.C. Monteiro ◽

Paulla G.M. Amorim ◽

Antonio L.B. Pinheiro

Keyword(s):

Bone Regeneration ◽

Bone Morphogenetic Proteins ◽

Bone Grafts ◽

Guided Bone Regeneration ◽

Rodent Model ◽

In Vivo Study ◽

Autologous Bone ◽

Autologous Bone Grafts

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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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