Bone tissue engineering with a collagen–hydroxyapatite scaffold and culture expanded bone marrow stromal cells

Abstract

Osteoprogenitor cells combined with supportive biomaterials represent a promising approach to advance the standard of care for bone grafting procedures. However, this approach faces challenges, including inconsistent bone formation, cell survival in the implant, and appropriate biomaterial degradation. We have developed a collagen–hydroxyapatite (HA) scaffold that supports consistent osteogenesis by donor derived osteoprogenitors, and is more easily degraded than a pure ceramic scaffold. Herein, the material properties are characterized as well as cell attachment, viability, and progenitor distribution in vitro. Furthermore, we examined the biological performance in vivo in a critical-size mouse calvarial defect. To aid in the evaluation of the in-house collagen–HA scaffold, the in vivo performance was compared with a commercial collagen–HA scaffold (Healos®, Depuy). The in-house collagen–HA scaffold supported consistent bone formation by predominantly donor-derived osteoblasts, nearly completely filling a 3.5 mm calvarial defect with bone in all samples (n=5) after 3 weeks of implantation. In terms of bone formation and donor cell retention at 3 weeks postimplantation, no statistical difference was found between the in-house and commercial scaffold following quantitative histomorphometry. The collagen–HA scaffold presented here is an open and well-defined platform that supports robust bone formation and should facilitate the further development of collagen–hydroxyapatite biomaterials for bone tissue engineering.

Biomimetic multidirectional scaffolds for zonal osteochondral tissue engineering via a lyophilization bonding approach

“…The Volume Fraction and Anisotropy tools within the BoneJ plugin suite for ImageJ were used to determine zonal porosity and anisotropy, respectively. Zonal interconnectivity (interconnected void volume/total void volume) was determined using the Volume Fraction and 3D Objects Counter, where a sphere‐filling algorithm (Thickness, BoneJ) was applied to close pores ≤15 µm, as pores of this size do not significantly contribute to mass transport …”

Photocrosslinkable and elastomeric hydrogels for bone regeneration

“…Among these nanomaterials, nanohydroxyapatite (nHAp) has been combined with various hydrophobic polymers to fabricate nanocomposite scaffolds. Mineralized tissues such as bone are composed of inorganic mineral (nHAp ∼69 wt %) and an organic component containing predominantly collagen . Thus, nHAp has been extensively investigated for a range of biomedical applications including bone tissue engineering, dental fillers, and drug delivery .…”

Improving the permeability of lyophilized collagen–hydroxyapatite scaffolds for cell‐based bone regeneration with a gelatin porogen

“…Bone marrow osteoprogenitors can be greatly expanded in culture, improving the therapeutic potency when higher numbers of osteoprogenitors are seeded to a site of bone injury . We have developed a collagen–hydroxyapatite (HA) scaffold that is osteogenic in preclinical in vivo models of cell‐based bone repair with culture‐expanded bone marrow osteoprogenitors – . However, the cellular morphology of lyophilized collagen‐based scaffolds can sometimes result in a relatively low permeability.…”