Anisotropic Cryostructured Collagen Scaffolds for Efficient Delivery of RhBMP–2 and Enhanced Bone Regeneration

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.

Spatio-temporal characterization of fracture healing patterns and assessment of biomaterials by time-lapsed in vivo micro-computed tomography

“…Although periosteal bone formation was more pronounced in the collagen group, the fracture healing outcome was not different between groups. This is in line with previous bone defect studies in different rodent models (loaded and non-loaded bones) reporting no significant effect of collagen scaffolds on bone regeneration with incomplete bone union or non-unions at the study end 30,31 . Similarly, in large animal models collagen scaffolds either failed to prevent non-unions 32 or to restore the mechanical bone properties 33 .…”

In situ mineralized PLGA/zwitterionic hydrogel composite scaffold enables high-efficiency rhBMP-2 release for critical-sized bone healing

“…S4 and Table S1†). 10,20,44,64–80 In our previous study, we developed a novel zwitterionic PLGA/PSBMA composite scaffold that enables robust functional healing of critical-sized bone defects with an ultralow rhBMP-2 dose of 400 ng per scaffold. 44 Given the improved in vitro sustained release of rhBMP-2 and the enhanced osteoinductivity observed on the m-PLGA/PSBMA scaffold vs. the PLGA/PSBMA scaffold, dosages of rhBMP-2 ranging from 0 to 450 ng per scaffold were applied on the m-PLGA/PSBMA composite scaffolds in the current study (Fig.…”

Long-Term Changes in Adipose Tissue in the Newly Formed Bone Induced by Recombinant Human BMP-2 In Vivo

“…Various scaffolds, such as collagen sponges, hydroxyapatite, and demineralized bovine bone, have been used as rhBMP-2 carriers [ 29 , 30 ]. In our previous in vivo study, rhBMP-2 was used with different forms of bone scaffolds, including particle- and block-type bovine bone, and adipose tissue and new bone formation were compared between the two groups [ 15 ].…”