title: In Vivo Host Response and Degradation of Copolymer Scaffolds Functionalized with Nanodiamonds and Bone Morphogenetic Protein 2.
abstract: The aim is to evaluate the effect of modifying poly[(l-lactide)-co-(ε-caprolactone)] scaffolds (PLCL) with nanodiamonds (nDP) or with nDP+physisorbed BMP-2 (nDP+BMP-2) on in vivo host tissue response and degradation. The scaffolds are implanted subcutaneously in Balb/c mice and retrieved after 1, 8, and 27 weeks. Molecular weight analysis shows that modified scaffolds degrade faster than the unmodified. Gene analysis at week 1 shows highest expression of proinflammatory markers around nDP scaffolds; although the presence of inflammatory cells and foreign body giant cells is more prominent around the PLCL. Tissue regeneration markers are highly expressed in the nDP+BMP-2 scaffolds at week 8. A fibrous capsule is detectable by week 8, thinnest around nDP scaffolds and at week 27 thickest around PLCL scaffolds. mRNA levels of ALP, COL1α2, and ANGPT1 are significantly upregulating in the nDP+BMP-2 scaffolds at week 1 with ectopic bone seen at week 8. Even when almost 90% of the scaffold is degraded at week 27, nDP are observable at implantation areas without adverse effects. In conclusion, modifying PLCL scaffolds with nDP does not aggravate the host response and physisorbed BMP-2 delivery attenuates inflammation while lowering the dose of BMP-2 to a relatively safe and economical level.
authors: Department of Clinical Dentistry, Center for Clinical Dental Research, University of Bergen, 5009, Bergen, Norway.|Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, 5020, Bergen, Norway.|Center for International Health, Department of Global Public Health and Primary Care, University of Bergen, 5009, Bergen, Norway.
authors: Salwa
authors: S
authors: Suliman
authors: Department of Fibre and Polymer Technology, KTH, Royal Institute of Technology, 10044, Stockholm, Sweden.
authors: Yang
authors: Y
authors: Sun
authors: Department of Clinical Dentistry, Center for Clinical Dental Research, University of Bergen, 5009, Bergen, Norway.
authors: Torbjorn O
authors: TO
authors: Pedersen
authors: Department of Clinical Dentistry, Center for Clinical Dental Research, University of Bergen, 5009, Bergen, Norway.
authors: Ying
authors: Y
authors: Xue
authors: Chair Tissue Engineering and Regenerative Medicine, University Hospital of Würzburg, 97070, Würzburg, Germany.|Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Translational Center "Regenerative Therapies for Oncology and Musculoskeletal Diseases"- Würzburg branch, D-97070, Würzburg, Germany.
authors: Joachim
authors: J
authors: Nickel
authors: Institute of Organic Chemistry, University of Würzburg, 97074, Würzburg, Germany.
authors: Thilo
authors: T
authors: Waag
authors: Department of Fibre and Polymer Technology, KTH, Royal Institute of Technology, 10044, Stockholm, Sweden.
authors: Anna
authors: A
authors: Finne-Wistrand
authors: DiaCoating GmbH, 6020, Innsbruck, Austria.
authors: Doris
authors: D
authors: Steinmüller-Nethl
authors: Institute of Organic Chemistry, University of Würzburg, 97074, Würzburg, Germany.
authors: Anke
authors: A
authors: Krueger
authors: Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, 5020, Bergen, Norway.|Center for International Health, Department of Global Public Health and Primary Care, University of Bergen, 5009, Bergen, Norway.|Department of Pathology, Hauekeland University Hospital, 5020, Bergen, Norway.
authors: Daniela E
authors: DE
authors: Costea
authors: Department of Clinical Dentistry, Center for Clinical Dental Research, University of Bergen, 5009, Bergen, Norway.
authors: Kamal
authors: K
authors: Mustafa
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000378:metabolism; D001861:Bone Regeneration / Q000502:physiology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000502:physiology; D018925:Chemokines / Q000172:deficiency / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D058612:Nanodiamonds / Q000737:chemistry*; D018919:Neovascularization, Physiologic; D011091:Polyesters / Q000737:chemistry*; D019736:Prostheses and Implants; D012867:Skin / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D018925:Chemokines; D016207:Cytokines; D058612:Nanodiamonds; D011091:Polyesters; C062968:lactide-caprolactone copolymer; D000469:Alkaline Phosphatase
keywords: BMP-2 delivery; biocompatibility; inflammation; tissue engineering