Abstract
In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing.
Highlights
Bone tissue is composed of specialized cells embedded in an extracellular matrix, which represents a hierarchical network assembled from two major components, collagen type I fibrils and hydroxyapatite nanocrystals, distributed along the collagen fibrils [1].Materials 2019, 12, 3105; doi:10.3390/ma12193105 www.mdpi.com/journal/materialsWhile the cortical bone bears an anisotropic microstructure, the trabecular bone features isotropic structural properties [2].Failure of the reparative process of bone tissue is a major clinical problem
The rhBMP–2 was produced inside modified Escherichia coli bacteria and purified according to previously published protocols [21]
The elementary composition of the resulting bone scaffolds was analyzed by Energy Dispersive
Summary
Bone tissue is composed of specialized cells (osteoblasts and osteocytes) embedded in an extracellular matrix, which represents a hierarchical network assembled from two major components, collagen type I fibrils and hydroxyapatite nanocrystals, distributed along the collagen fibrils [1]. Failure of the reparative process of bone tissue is a major clinical problem. Anatomical location of the fractured bone, and associated comorbidities of the patient may interfere with the normal process of repair, resulting in fracture nonunion, delayed union, or malunion. Fracture nonunion is a cause of chronic pain and disability, while being associated with increased healthcare cost and loss of working days [3]. The gold standard for the treatment of non-unions is based on the use of bone autografts, but supply is limited and allograft substitutes lack osteoinductive and osteogenic properties [4]
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