title: Biodegradation, biocompatibility, and osteoconduction evaluation of collagen-nanohydroxyapatite cryogels for bone tissue regeneration.
abstract: Designing biomimetic biomaterials inspired by the natural complex structure of bone and other hard tissues is still a challenge nowadays. The control of the biomineralization process onto biomaterials should be evaluated before clinical application. Aiming at bone regeneration applications, this work evaluated the in vitro biodegradation and interaction between human bone marrow stromal cells (HBMSC) cultured on different collagen/nanohydroxyapatite cryogels. Cell proliferation, differentiation, morphology, and metabolic activity were assessed through different protocols. All the biocomposite materials allowed physiologic apatite deposition after incubation in simulated body fluid and the cryogel with the highest nanoHA content showed to have the highest mechanical strength (DMA). The study clearly showed that the highest concentration of nanoHA granules on the cryogels were able to support cell type's survival, proliferation, and individual functionality in a monoculture system, for 21 days. In fact, the biocomposites were also able to differentiate HBMSCs into osteoblastic phenotype. The composites behavior was also assessed in vivo through subcutaneous and bone implantation in rats to evaluate its tissue-forming ability and degradation rate. The cryogels Coll/nanoHA (30 : 70) promoted tissue regeneration and adverse reactions were not observed on subcutaneous and bone implants. The results achieved suggest that scaffolds of Coll/nanoHA (30 : 70) should be considered promising implants for bone defects that present a grotto like appearance with a relatively small access but a wider hollow inside. This material could adjust to small dimensions and when entering into the defect, it could expand inside and remain in close contact with the defect walls, thus ensuring adequate osteoconductivity.
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|INEB - Instituto De Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180, Porto, Portugal.|Faculdade De Engenharia, Departamento De Engenharia Metalúrgica e Materiais, Universidade do Porto, Rua Dr. Roberto Frias, S/N 4200-465, Porto, Portugal.
authors.forename: Christiane Laranjo
authors.initials: CL
authors.lastname: Salgado
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|INEB - Instituto De Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180, Porto, Portugal.|Faculdade De Engenharia, Departamento De Engenharia Metalúrgica e Materiais, Universidade do Porto, Rua Dr. Roberto Frias, S/N 4200-465, Porto, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Grenho
authors.affiliation: Laboratory for Bone Metabolism and Regeneration, Faculdade De Medicina Dentária Da Universidade Do Porto (FMDUP), Rua Dr. Manuel Pereira Da Silva, 4200-393, Porto, Portugal.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Fernandes
authors.affiliation: Department of Zootechny, Center for the Study of Animal Sciences (CECA), ECAV, Universidade De Trás-os-Montes E Alto Douro, 5001-801, Vila Real, Portugal.
authors.forename: Bruno Jorge
authors.initials: BJ
authors.lastname: Colaço
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|INEB - Instituto De Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180, Porto, Portugal.|Faculdade De Engenharia, Departamento De Engenharia Metalúrgica e Materiais, Universidade do Porto, Rua Dr. Roberto Frias, S/N 4200-465, Porto, Portugal.
authors.forename: Fernando Jorge
authors.initials: FJ
authors.lastname: Monteiro
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology* / Q000648:ultrastructure; D059985:Cryogels / Q000494:pharmacology*; D017886:Durapatite / Q000494:pharmacology*; D055119:Elastic Modulus / Q000187:drug effects; D020007:Implants, Experimental; D008297:Male; D008422:Materials Testing / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D016348:Osseointegration / Q000187:drug effects*; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D059985:Cryogels; C509317:nano-hydroxyapatite-collagen; D003094:Collagen; D017886:Durapatite; D000469:Alkaline Phosphatase
keywords: biomimetic material; bone regeneration; collagen; nanohydroxyapatite