Bioactive cell-derived matrices combined with polymer mesh scaffold for osteogenesis and bone healing.
Successful bone tissue engineering generally requires an osteoconductive scaffold that consists of extracellular matrix (ECM) to mimic the natural environment. In this study, we developed a PLGA/PLA-based mesh scaffold coated with cell-derived extracellular matrix (CDM) for the delivery of bone morphogenic protein (BMP-2), and assessed the capacity of this system to provide an osteogenic microenvironment. Decellularized ECM from human lung fibroblasts (hFDM) was coated onto the surface of the polymer mesh scaffolds, upon which heparin was then conjugated onto hFDM via EDC chemistry. BMP-2 was subsequently immobilized onto the mesh scaffolds via heparin, and released at a controlled rate. Human placenta-derived mesenchymal stem cells (hPMSCs) were cultured in such scaffolds and subjected to osteogenic differentiation for 28 days in vitro. The results showed that alkaline phosphatase (ALP) activity, mineralization, and osteogenic marker expression were significantly improved with hPMSCs cultured in the hFDM-coated mesh scaffolds compared to the control and fibronectin-coated ones. In addition, a mouse ectopic and rat calvarial bone defect model was used to examine the feasibility of current platform to induce osteogenesis as well as bone regeneration. All hFDM-coated mesh groups exhibited a significant increase of newly formed bone and in particular, hFDM-coated mesh scaffold loaded with a high dose of BMP-2 exhibited a nearly complete bone defect healing as confirmed via micro-CT and histological observation. This work proposes a great potency of using hFDM (biophysical) coupled with BMP-2 (biochemical) as a promising osteogenic microenvironment for bone tissue engineering applications.
Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
In Gul
IG
Kim
Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
Mintai P
MP
Hwang
Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Dept of Biomedical Engineering, Korea University of Science and Technology, Daejeon 305-350, Republic of Korea.
Ping
P
Du
Dept of Technical Application, Korea Institute of Industrial Technology, Gyeonggi 1271-18, Republic of Korea.
Jaehoon
J
Ko
Dept of Orthopedic Surgery, Samsung Medical Center, Stem Cell and Regenerative Medicine Center, Sungkyunkwan University School of Medicine, Seoul 136-710, Republic of Korea.
Chul-won
CW
Ha
Dept of Veterinary Medicine, KonKuk University, Seoul 143-701, Republic of Korea.
Sun Hee
SH
Do
Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Dept of Biomedical Engineering, Korea University of Science and Technology, Daejeon 305-350, Republic of Korea. Electronic address: kpark@kist.re.kr.
Kwideok
K
Park
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D008819:Mice, Nude; D016348:Osseointegration / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010920:Placenta / Q000166:cytology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects / Q000473:pathology; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D055767:Immobilized Proteins; D011108:Polymers; D002118:Calcium
Bone morphogenic protein (BMP)-2; Bone tissue engineering; Cell-derived matrix; Extracellular matrix (ECM); Microenvironment; Polymer mesh scaffold