Polydopamine-assisted osteoinductive peptide immobilization of polymer scaffolds for enhanced bone regeneration by human adipose-derived stem cells.
Immobilization of osteoinductive molecules, including growth factors or peptides, on polymer scaffolds is critical for improving stem cell-mediated bone tissue engineering. Such molecules provide osteogenesis-stimulating signals for stem cells. Typical methods used for polymeric scaffold modification (e.g., chemical conjugation or physical adsorption), however, have limitations (e.g., multistep, complicated procedures, material denaturation, batch-to-batch inconsistency, and inadequate conjugation) that diminish the overall efficiency of the process. Therefore, in this study, we report a biologically inspired strategy to prepare functional polymer scaffolds that efficiently regulate the osteogenic differentiation of human adipose-derived stem cells (hADSCs). Polymerization of dopamine (DA), a repeated motif observed in mussel adhesive protein, under alkaline pH conditions, allows for coating of a polydopamine (pDA) layer onto polymer scaffolds. Our study demonstrates that predeposition of a pDA layer facilitates highly efficient, simple immobilization of peptides derived from osteogenic growth factor (bone morphogenetic protein-2; BMP-2) on poly(lactic-co-glycolic acid) (PLGA) scaffolds via catechol chemistry. The BMP-2 peptide-immobilized PLGA scaffolds greatly enhanced in vitro osteogenic differentiation and calcium mineralization of hADSCs using either osteogenic medium or nonosteogenic medium. Furthermore, transplantation of hADSCs using pDA-BMP-2-PLGA scaffolds significantly promoted in vivo bone formation in critical-sized calvarial bone defects. Therefore, pDA-mediated catechol functionalization would be a simple and effective method for developing tissue engineering scaffolds exhibiting enhanced osteoinductivity. To the best of our knowledge, this is the first study demonstrating that pDA-mediated surface modification of polymer scaffolds potentiates the regenerative capacity of human stem cells for healing tissue defect in vivo.
Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Eunkyung
E
Ko
Kisuk
K
Yang
Jisoo
J
Shin
Seung-Woo
SW
Cho
D000273:Adipose Tissue / Q000166:cytology; D053687:Adult Stem Cells / Q000502:physiology* / Q000637:transplantation; D000595:Amino Acid Sequence; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000494:pharmacology; D001861:Bone Regeneration; D002454:Cell Differentiation; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003094:Collagen / Q000378:metabolism; D005260:Female; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010012:Osteogenesis; D053495:Osteopontin / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011859:Radiography; D044968:Regenerative Medicine; D012886:Skull / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D013499:Surface Properties
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D020099:Coated Materials, Biocompatible; D055767:Immobilized Proteins; D007211:Indoles; D010446:Peptide Fragments; D011108:Polymers; C568283:polydopamine; D053495:Osteopontin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen