The inclusion of zinc into mineralized collagen scaffolds for craniofacial bone repair applications

• Published in: Acta biomaterialia 2019-07, Vol.93, p.86-96
• Main Authors: Tiffany, Aleczandria S., Gray, Danielle L., Woods, Toby J., Subedi, Kiran, Harley, Brendan A.C.
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Biocompatibility; Biomaterials; Biomedical materials; Bone; Bone growth; Bone healing; Bone implants; Bone Regeneration; Calcification, Physiologic; Cells, Cultured; Collagen; Collagen - chemistry; Collagen scaffold; Compression; Compression tests; Differentiation (biology); Facial Injuries - metabolism; Facial Injuries - pathology; Facial Injuries - therapy; Glycosaminoglycans; In vivo methods and tests; Inductively coupled plasma mass spectrometry; Kinetics; Mass spectrometry; Mass spectroscopy; Materials Testing; Mechanical properties; Mechanical tests; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Mineral; Mineralization; Modulus of elasticity; Morphology; Osteogenesis; Regeneration; Regeneration (physiology); Scaffolds; Scanning electron microscopy; Scanning transmission electron microscopy; Stem cell transplantation; Stem cells; Surgical implants; Swine; Tissue engineering; Tissue Scaffolds - chemistry; Trace elements; X-ray diffraction; Zinc; Zinc - chemistry; Zinc sulfate
• ISSN: 1742-7061; 1878-7568; 1878-7568
• DOI: 10.1016/j.actbio.2019.05.031

[Display omitted] Implant osteoinduction and subsequent osteogenic activity are critical events that need improvement for regenerative healing of large craniofacial bone defects. Here we describe the augmentation of the mineral content of a class of mineralized collagen scaffolds under development for craniomaxillofacial bone regeneration via the inclusion of zinc ions to promote osteogenesis in vitro. Zinc is an essential trace element in skeletal tissue and bone, with soluble zinc being shown to promote osteogenic differentiation of porcine adipose derived stem cells. We report the development of a new class of zinc functionalized scaffolds fabricated by adding zinc sulfate to a mineralized collagen-glycosaminoglycan precursor suspension that was then freeze dried to form a porous biomaterial. We report analysis of zinc functionalized scaffolds via imaging (scanning electron microscopy), mechanical testing (compression), and compositional (X-ray diffraction, inductively coupled plasma mass spectrometry) analyses. Notably, zinc-functionalized scaffolds display morphological changes to the mineral phase and altered elastic modulus without substantially altering the composition of the brushite phase or removing the micro-scale pore morphology of the scaffold. These scaffolds also display zinc release kinetics on the order of days to weeks and promote successful growth and pro-osteogenic capacity of porcine adipose derived stem cells cultured within these zinc scaffolds. Taken together, we believe that zinc functionalized scaffolds provide a unique platform to explore strategies to improve in vivo osteogenesis in craniomaxillofacial bone injuries models. Craniomaxillofacial bone defects that arise from traumatic, congenital, and post-oncologic origins cannot heal on their own and often require surgical intervention. We have developed a class of mineralized collagen scaffolds that promotes osteogenesis and bone regeneration. Here we describe the inclusion of zinc sulfate into the mineralized collagen scaffold to improve osteogenesis. Zinc functionalized scaffolds demonstrate altered crystallite microstructure but consistent Brushite chemistry, improved mechanics, and promote zinc transporter expression while supporting stem cell viability, osteogenic differentiation, and mineral biosynthesis.