Low Dose BMP2-Doped Calcium Phosphate Graft Promotes Bone Defect Healing in a Large Animal Model

Background: Bone grafts are in high demand due to the increase in the cases of bone defects mainly caused by trauma, old age, and disease-related bone damages. Tissue-engineered calcium phosphate (CaP) biomaterials match the major inorganic contents of bone, thereby could be the potential bone graft substitute. However, CaP-bone grafts lack the osteoinductivity that is vital for effective bone regeneration. In this study, we aimed to test the bone defect healing potential of biomimetically fabricated low dose BMP2-doped CaP (BMP2.BioCaP) grafts in a large animal model.Methods: Low dose BMP2 was doped internally (BMP2-int.BioCaP) or on the surface of CaP (BMP2-sur.BioCaP) grafts during the fabrication process. Our previous study showed the robust bone regenerative potential of BMP2-int.BioCaP and BMP2-sur.BioCaP grafts in the rat ectopic model. In this study, we investigated the bone defect healing potential of BMP2.BioCaP grafts in sheep humerus/femoral defects, as well as compared with that of autologous bone graft and clinically used deproteinized bovine bone (DBB) xenograft.Results: Different ways of BMP2 doping did not affect the surface morphology and degradation properties of the graft materials. Micro-CT and histology results showed robustly higher bone defect-healing potential of the BMP2.BioCaP grafts compared to clinically used DBB grafts. The bone defect healing potential of BMP2.BioCaP grafts was as effective as that of the autologous bone graft. Although, BMP2-int.BioCaP doped half the amount of BMP2 compared to BMP2-sur.BioCaP, its' bone defect healing potential was even robust. The BMP2.BioCaP grafts showed less immunogenicity compared to BioCaP or DBB grafts. The volume density of blood vessel-like and bone marrow-like structures in both BMP2.BioCaP graft groups were in a similar extent to the autologous group. Meticulous observation of higher magnification histological images showed active bone regeneration and remodeling during bone defect healing in BMP2.BioCaP graft groups.Conclusion: The robust bone regenerative potential of BMP2.BioCaP grafts in the ectopic model and in-situ bone defects in small and large animals warrant the pre-clinical studies on large animal critical-sized segmental bone defects.

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Reconstruction of the glenoid using autologous bone-graft and the SMR Axioma TT metal-backed prosthesis

The Bone & Joint Journal ◽

10.1302/0301-620x.100b12.bjj-2018-0494.r1 ◽

2018 ◽

Vol 100-B (12) ◽

pp. 1609-1617 ◽

Cited By ~ 9

Author(s):

A. M. Malhas ◽

J. Granville-Chapman ◽

P. M. Robinson ◽

S. Brookes-Fazakerley ◽

M. Walton ◽

...

Keyword(s):

Bone Graft ◽

Reliable Method ◽

Titanium Surface ◽

Bone Defects ◽

Autologous Bone Graft ◽

Short Term ◽

Bone Deficiency ◽

Autologous Bone ◽

Shoulder Arthroplasties

Aims We present our experience of using a metal-backed prosthesis and autologous bone graft to treat gross glenoid bone deficiency. Patients and Methods A prospective cohort study of the first 45 shoulder arthroplasties using the SMR Axioma Trabecular Titanium (TT) metal-backed glenoid with autologous bone graft. Between May 2013 and December 2014, 45 shoulder arthroplasties were carried out in 44 patients with a mean age of 64 years (35 to 89). The indications were 23 complex primary arthroplasties, 12 to revise a hemiarthroplasty or resurfacing, five for aseptic loosening of the glenoid, and five for infection. Results Of the 45 patients, 16 had anatomical shoulder arthroplasties (ASA) and 29 had reverse shoulder arthroplasties (RSA). Postoperatively, 43/45 patients had a CT scan. In 41 of 43 patients (95%), the glenoid peg achieved > 50% integration. In 40 of 43 cases (93%), the graft was fully or partially integrated. There were seven revisions (16%) but only four (9%) required a change of baseplate. Four (25%) of the 16 ASAs were revised for instability or cuff failure. At two-year radiological follow-up, five of the 41 cases (11%) showed some evidence of lucent lines. Conclusion The use of a metal baseplate with a trabecular titanium surface in conjunction with autologous bone graft is a reliable method of addressing glenoid bone defects in primary and revision RSA setting in the short term. ASAs have a higher rate of complications with this technique.

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Autologous bone marrow clot as an alternative to autograft for bone defect healing

Bone and Joint Research ◽

10.1302/2046-3758.83.bjr-2018-0096.r1 ◽

2019 ◽

Vol 8 (3) ◽

pp. 107-117 ◽

Cited By ~ 8

Author(s):

Z. X. H. Lim ◽

B. Rai ◽

T. C. Tan ◽

A. K. Ramruttun ◽

J. H. Hui ◽

...

Keyword(s):

Bone Marrow ◽

Bone Defect ◽

Autologous Bone Marrow ◽

Defect Healing ◽

Bone Defect Healing ◽

Autologous Bone

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Critical Size Bone Defect Healing Using Collagen–Calcium Phosphate Bone Graft Materials

PLoS ONE ◽

10.1371/journal.pone.0168883 ◽

2017 ◽

Vol 12 (1) ◽

pp. e0168883 ◽

Cited By ~ 18

Author(s):

William Robert Walsh ◽

Rema A. Oliver ◽

Chris Christou ◽

Vedran Lovric ◽

Emma Rose Walsh ◽

...

Keyword(s):

Calcium Phosphate ◽

Bone Graft ◽

Bone Defect ◽

Critical Size ◽

Defect Healing ◽

Bone Defect Healing

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Bone morphogenetic protein 2-induced cellular chemotaxis drives tissue patterning during critical-sized bone defect healing: an in silico study

Biomechanics and Modeling in Mechanobiology ◽

10.1007/s10237-021-01466-0 ◽

2021 ◽

Author(s):

Edoardo Borgiani ◽

Georg N. Duda ◽

Bettina M. Willie ◽

Sara Checa

Keyword(s):

Bone Tissue ◽

Bone Defect ◽

Computer Model ◽

In Silico ◽

Bone Defects ◽

Bone Morphogenetic Protein 2 ◽

Defect Healing ◽

Tissue Patterning ◽

Bone Defect Healing

AbstractCritical-sized bone defects are critical healing conditions that, if left untreated, often lead to non-unions. To reduce the risk, critical-sized bone defects are often treated with recombinant human BMP-2. Although enhanced bone tissue formation is observed when BMP-2 is administered locally to the defect, spatial and temporal distribution of callus tissue often differs from that found during regular bone healing or in defects treated differently. How this altered tissue patterning due to BMP-2 treatment is linked to mechano-biological principles at the cellular scale remains largely unknown. In this study, the mechano-biological regulation of BMP-2-treated critical-sized bone defect healing was investigated using a multiphysics multiscale in silico approach. Finite element and agent-based modeling techniques were combined to simulate healing within a critical-sized bone defect (5 mm) in a rat femur. Computer model predictions were compared to in vivo microCT data outcome of bone tissue patterning at 2, 4, and 6 weeks postoperation. In vivo, BMP-2 treatment led to complete healing through periosteal bone bridging already after 2 weeks postoperation. Computer model simulations showed that the BMP-2 specific tissue patterning can be explained by the migration of mesenchymal stromal cells to regions with a specific concentration of BMP-2 (chemotaxis). This study shows how computational modeling can help us to further understand the mechanisms behind treatment effects on compromised healing conditions as well as to optimize future treatment strategies.

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Bilateral total knee replacement in severe knee osteoarthritis with large bone defect using autologous bone graft augmentation

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v15i1.1266 ◽

2016 ◽

Vol 15 (1) ◽

Author(s):

Mohd Shahidan Noor Rahin ◽

Khairul Nizam Siron ◽

Ed Simor Khan Mor Japar Khan ◽

Ahmad Hafiz Zulkifly ◽

Nik Fatmy Nik Najmy

Keyword(s):

Bone Graft ◽

Bone Defect ◽

Knee Replacement ◽

Radiological Finding ◽

Varus Deformity ◽

Autologous Bone Graft ◽

Left Knee ◽

Range Of Movement ◽

Bilateral Knee ◽

Autologous Bone

40 years old malay gentleman with underlying gout presenting with severe pain in both knees for 10 years, analgesic dependant and wheelchair ambulation. Examination of right knee shows fixed flexion at 10 degrees, range of movement 10-100 degree flexion, lateral collateral laxity and varus deformity. Left knee had fixed flexion at 10 degrees, range of movement 5-100 degree and varus deformity. Blood investigation showed uric acid. X-ray of bilateral knee showed severe tricompartmental arthritis with large medial tibial defect. The patient has undergone bilateral knee replacement in 5 months interval started with left knee. Surgical technique is the same for both knees, intraoperative shows a large posteromedial bone defect. We used 5mm metal augmentation on the right knee, but due to limited financial resources, we have to use the bone graft from the osteotomized bone for the augmentation on the left side. The bone augmentation was fixed with cancellous screw. The patient was referred to physiotherapy for range of motion exercises. 1 year post operatively patient able to ambulate without aid. Pain score improved. The patient does not require analgesia. Functional and knee score is excellent. Range of movement, bilateral knee are 0-100 degree. Radiological finding shows no evidence of construct failure in both metal block and bone graft construct. Severe arthritis with bone defect is common due to late presentation. Using autologous bone graft can provide good result as using expensive meta block for reconstruction.

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Reconstructing Bone with Natural Bone Graft: A Review of In Vivo Studies in Bone Defect Animal Model

Nanomaterials ◽

10.3390/nano8120999 ◽

2018 ◽

Vol 8 (12) ◽

pp. 999 ◽

Cited By ~ 10

Author(s):

Mengying Liu ◽

Yonggang Lv

Keyword(s):

Bone Graft ◽

Bone Defect ◽

Bone Structure ◽

Demineralized Bone Matrix ◽

Bone Matrix ◽

Bone Defects ◽

Autologous Bone Graft ◽

In Vivo Studies ◽

Natural Bone

Bone defects caused by fracture, disease or congenital defect remains a medically important problem to be solved. Bone tissue engineering (BTE) is a promising approach by providing scaffolds to guide and support the treatment of bone defects. However, the autologous bone graft has many defects such as limited sources and long surgical procedures. Therefore, xenograft bone graft is considered as one of the best substitutions and has been effectively used in clinical practice. Due to better preserved natural bone structure, suitable mechanical properties, low immunogenicity, good osteoinductivity and osteoconductivity in natural bone graft, decellularized and demineralized bone matrix (DBM) scaffolds were selected and discussed in the present review. In vivo animal models provide a complex physiological environment for understanding and evaluating material properties and provide important reference data for clinical trials. The purpose of this review is to outline the in vivo bone regeneration and remodeling capabilities of decellularized and DBM scaffolds in bone defect models to better evaluate the potential of these two types of scaffolds in BTE. Taking into account the limitations of the state-of-the-art technology, the results of the animal bone defect model also provide important information for future design of natural bone composite scaffolds.

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