Guided tissue engineering for healing of cancellous and cortical bone using a combination of biomaterial based scaffolding and local bone active molecule delivery

Raina, Deepak; Qayoom, Irfan; Larsson, David; Zheng, Minghao; Kumar, Ashok; Isaksson, Hanna; Lidgren, Lars; Tägil, Magnus

doi:10.1016/j.biomaterials.2018.10.004

Cited by 68 publications

(51 citation statements)

References 37 publications

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“…In addition, a greater number of groups and specimens studied, provided they are ethically approved, can also be considered a limiting factor. We list as future studies the analysis and quantification of collagen fibers [78] and comparison between different concentrations of biopolymer in order to verify its osteogenic characteristics.…”

Section: Limitationsmentioning

confidence: 99%

Photobiomodulation Therapy Associated with Heterologous Fibrin Biopolymer and Bovine Bone Matrix Helps to Reconstruct Long Bones

et al. 2020

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Bone defects cause aesthetic and functional changes that affect the social, economic and especially the emotional life of human beings. This complication stimulates the scientific community to investigate strategies aimed at improving bone reconstruction processes using complementary therapies. Photobiomodulation therapy (PBMT) and the use of new biomaterials, including heterologous fibrin biopolymer (HFB), are included in this challenge. The objective of the present study was to evaluate the influence of photobiomodulation therapy on bone tibial reconstruction of rats with biomaterial consisting of lyophilized bovine bone matrix (BM) associated or not with heterologous fibrin biopolymer. Thirty male rats were randomly separated into three groups of 10 animals. In all animals, after the anesthetic procedure, a noncritical tibial defect of 2 mm was performed. The groups received the following treatments: Group 1: BM + PBMT, Group 2: BM + HFB and Group 3: BM + HFB + PBMT. The animals from Groups 1 and 3 were submitted to PBMT in the immediate postoperative period and every 48 h until the day of euthanasia that occurred at 14 and 42 days. Analyses by computed microtomography (µCT) and histomorphometry showed statistical difference in the percentage of bone formation between Groups 3 (BM + HB + PBMT) and 2 (BM + HFB) (26.4% ± 1.03% and 20.0% ± 1.87%, respectively) at 14 days and at 42 days (38.2% ± 1.59% and 31.6% ± 1.33%, respectively), and at 42 days there was presence of bone with mature characteristics and organized connective tissue. The µCT demonstrated BM particles filling the defect and the deposition of new bone in the superficial region, especially in the ruptured cortical. It was concluded that the association of PBMT with HFB and BM has the potential to assist in the process of reconstructing bone defects in the tibia of rats.

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Section: Limitationsmentioning

confidence: 99%

Photobiomodulation Therapy Associated with Heterologous Fibrin Biopolymer and Bovine Bone Matrix Helps to Reconstruct Long Bones

et al. 2020

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Section: Guided Bone Regeneration (Gbr) Is An Established Technique Imentioning

confidence: 99%

“…CelGro™ was shown to facilitate bridging the gap of a cortical bone defect (13) and improve vascularization (14). The induction of cortical bone regeneration was evaluated using a combination of CelGro™ and recombinant human bone morphogenic protein-2 (BMP-2), which was found to significantly improve repair of both cancellous and cortical metaphyseal defects (13). Since CelGro™ has been shown to induce cellular recruitment, upregulate proosteogenic factors at the implant site (15) (16) and promote vascularization (17), we hypothesized that CelGro™ alone, without growth factors such as BMP-2, is able to directly participate in repair of cortical defects through osseointegration property.…”

Section: Guided Bone Regeneration (Gbr) Is An Established Technique Imentioning

confidence: 99%

Collagen Membrane for Guided Cortical Bone Regeneration: Characterization, Preclinical and Proof of Concept Clinical Studies

Allan

Ruan

Landao-Bassonga

et al. 2020

Preprint

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Background: Treatment of cortical bone defects is a clinical challenge. Guided bone regeneration (GBR), commonly used in oral in maxillofacial dental surgery, may show promise for orthopedic application in repair of cortical defects. However, a limitation in the use of GBR for cortical bone defects is the lack of an ideal scaffold that provides sufficient mechanical support to bridge the cortical bone with minimal interference in the repair process. We have developed a new collagen membrane, CelGroTM, for use in GBR. We report the material characterisation of CelGroTM, and evaluate the performance of CelGroTM in translational preclinical and clinical studies. Methods: Scanning electron microscopy (SEM), micro computed tomography (micro-CT) and transmission electron microscopy (TEM) were used to examine the structural morphology of CelGroTM. Purity and biochemical composition of CelGroTM was evaluated by Western-blot, immunohistochemistry and confocal microscopy. Physical and chemical properties of CelGroTM were examined and compared with another commercially available collagen membrane. The pre-clinical evaluation was conducted using a cortical bone defect model in the New Zealand white rabbit. Cortical bone regeneration in defects of the femoral diaphysis were evaluated at 30 days and 60 days after intervention, by micro-CT and histology. A clinical study to evaluate the performance of CelGroTM in GBR for treatment of bone augmentation surrounding dental implants was also performed. The clinical outcomes were evaluated by semi quantitative tissue condition assessments and cone-beam computed tomography (CBCT) scan. Results: CelGroTM has a bilayer structure of different fibre alignment and is composed almost exclusively of type I collagen. CelGroTM was found to be completely acellular and a clinically significant xenoantigen, α -gal, was not detected. CelGroTM displayed less deformity and better mechanical strength as compared to Bio-Gide ® . In the preclinical study, CelGroTM demonstrated enhanced bone-modelling activity and cortical bone healing. Micro-CT evaluation showed early bony bridging over the defect area 30 days post-operatively, and nearly complete restoration of mature cortical bone at the bone defect site 60 days post- operatively. Histological analysis at day 60 after surgery further confirmed that CelGroTM enables bridging of the cortical bone defect by induction of newly-formed cortical bone. It appears that CelGroTM showed better cortical alignment and reduced porosity at the defect interface compared to Bio-Gide®. Owning the fact that selection of orthopedic patients with cortical bone defects is complex, we conducted the proof of concept clinical study in a total of 16 dental implants which were placed in 10 participants receiving GBR. The results showed that there were with no complications or adverse events observed. CBCT evidenced efficiency of the CelGroTM scaffold for GBR for the dental implants, showing significantly decreased 2 distance from the implant shoulder to first bone/implant contact (DIB) and increased horizontal thickness of facial bone wall (HT). Conclusion: The findings of our study demonstrate that CelGroTM is an ideal membrane for GBR not only in oral maxillofacial reconstructive surgery but also in orthopedic applications. Details of clinical trial registration: “Single centre, open-label, pilot study of Celgro(tm) collagen membrane for guided bone regeneration around exposed implants in patients undergoing dental implant surgery”; Registration ID: ACTRN12615000027516; Date of registration: 19/01/2015; URL: https://anzctr.org.au/ACTRN12615000027516.aspx

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“…Since bisphosphonates have shown to be effective, recent pre-clinical research has focused on delivering ZA systemically or locally at the desired site, primarily aimed at increasing implant anchorage with the surrounding bone (11)(12)(13). Studies have also indicated that local usage of low dose ZA in cancellous bone, such as an experimentally created metaphyseal void, surprisingly lead to improved bone formation in rodent models (14). The notion of bisphosphonates such as ZA being only anti-catabolic needs to be redefined since they also impart a dose dependent pseudo-anabolic effect on cancellous bone.…”

Section: Introductionmentioning

confidence: 99%

“…The notion of bisphosphonates such as ZA being only anti-catabolic needs to be redefined since they also impart a dose dependent pseudo-anabolic effect on cancellous bone. Several pre-clinical trials with carriers containing ZA providing controlled local delivery have shown regeneration of cancellous bone without the addition of bone morphogenic proteins (BMPs) (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Response to a Bioactive Biphasic Biomaterial in the Femoral Neck of Osteoporotic Rats

Raina

Širka

Qayoom

et al. 2020

Tissue Engineering Part A

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Osteoporosis often leads to fragility fractures of the hip resulting in impaired quality of life and increased mortality. Augmenting the proximal femur could be an attractive option for prevention of fracture or fixation device failure. We describe a tissue engineering based strategy to enhance long-term bone formation in the femoral neck of osteoporotic rats by locally delivering bioactive molecules; bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) using a calcium sulphate/hydroxyapatite (CaS/HA) biomaterial. A defect was created by reaming the femoral neck canal of osteoporotic (OVX) rats and they were treated as follows: G1. Empty, G2. CaS/HA, G3. CaS/HA + Systemic ZA, G4. CaS/HA + Local ZA and G5. CaS/HA + Local ZA + rhBMP-2. Bone formation was evaluated 6 months after treatment. Furthermore, radioactively labelled 14 C-ZA was used to study the bioavailability of ZA at the defect location, which was determined using scintillation counting. Micro-CT indicated significantly higher bone volume (BV) in groups G4 and G5 compared to the other treatment groups. This was confirmed qualitatively by histological assessment. Addition of rhBMP-2 gave no additional benefit in this model. Local delivery of ZA performed better than systemic administration of ZA. Mechanical testing showed no differences between the groups, likely reflecting that the addition of bioactive molecules had limited effect on cortical bone or the choice of mechanical testing setup was not optimal. Scintillation counting revealed higher amounts of 14 C-ZA present in the treated leg of G4 compared to its contralateral control and compared to G3 indicating that local ZA delivery can be used to achieve high local concentrations without causing a systemic effect. This long-term study shows that local delivery of ZA using a CaS/HA carrier can regenerate cancellous bone in the femoral neck canal and has clear implications for enhancing implant integration and fixation in fragile bone.

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Guided tissue engineering for healing of cancellous and cortical bone using a combination of biomaterial based scaffolding and local bone active molecule delivery

Cited by 68 publications

References 37 publications

Photobiomodulation Therapy Associated with Heterologous Fibrin Biopolymer and Bovine Bone Matrix Helps to Reconstruct Long Bones

Photobiomodulation Therapy Associated with Heterologous Fibrin Biopolymer and Bovine Bone Matrix Helps to Reconstruct Long Bones

Collagen Membrane for Guided Cortical Bone Regeneration: Characterization, Preclinical and Proof of Concept Clinical Studies

Long-Term Response to a Bioactive Biphasic Biomaterial in the Femoral Neck of Osteoporotic Rats

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