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Biomaterials as carriers for bone active molecules-An approach to create off-the-shelf bone substitutes

Author: Raina, Deepak
Publisher: Lund University: Faculty of Medicine 2018
Edition/Format:   Downloadable archival material : English
Summary:
Bone tissue is commonly transplanted during orthopedic surgeries, primarily for the management of bone defects caused by trauma or various orthopedic conditions including, but not limited to, infections and tumours. Bone grafts are a surgeon’s choice, but their associated drawbacks are paving the way for biomaterial based bone graft substitutes. Biomaterials inherently lack the ability to induce significant amount  Read more...
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Genre/Form: thesis/doccomp
info:eu-repo/semantics/doctoralThesis
text
Document Type: Archival Material
All Authors / Contributors: Raina, Deepak
OCLC Number: 1065536983
Language Note: English
Notes: application/pdf

Abstract:

Bone tissue is commonly transplanted during orthopedic surgeries, primarily for the management of bone defects caused by trauma or various orthopedic conditions including, but not limited to, infections and tumours. Bone grafts are a surgeon’s choice, but their associated drawbacks are paving the way for biomaterial based bone graft substitutes. Biomaterials inherently lack the ability to induce significant amount of bone growth due to which they may be combined with cells, biomaterials, growth factors and drugs to regenerate functional bone tissue. This thesis focused on characterizing biomaterial carriers that can locally deliver bone active molecules for bone regeneration and potentially act as an alternative to conventional bone grafting. We focused on the delivery of recombinant human bone morphogenic protein-2 (rhBMP-2) as a bone inducing anabolic growth factor. Simultaneously, we have used an osteoclast inhibiting bisphosphonate, zoledronic acid (ZA) to prevent BMP-2 induced premature bone resorption. Three different biomaterials scaffolds; a microporous calcium sulphate (CaS)/hydroxyapatite (HA), a macroporous gelatin-CaS/HA and a collagen membrane were used in distinct animal models of bone regeneration.The carrier properties of the three biomaterials in the ectopic muscle pouch model (studies 1, 4 and 5) showed that the tested materials were efficient carriers of rhBMP-2 and ZA and that co-delivery of rhBMP-2 and ZA regenerated higher volume of bone compared to rhBMP-2 alone. Studies 2& 3 show that the CaS/HA material locally delivering ZA or ZA+rhBMP-2 could be efficiently used for bone regeneration in clinically relevant bone defect models. These studies also indicated that local delivery of ZA not only has an anti-osteoclast effect but it also has an anabolic role. Study 4 compared the developed porous biomaterial with the current FDA approved collagen sponge and results indicated that the developed biomaterial outperforms the current marketed product f

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