title: In vivo biocompatibility and biodegradation of 3D-printed porous scaffolds based on a hydroxyl-functionalized poly(ε-caprolactone).
abstract: The aim of this study was to evaluate the in vivo biodegradation and biocompatibility of three-dimensional (3D) scaffolds based on a hydroxyl-functionalized polyester (poly(hydroxymethylglycolide-co-ε-caprolactone), PHMGCL), which has enhanced hydrophilicity, increased degradation rate, and improved cell-material interactions as compared to its counterpart poly(ε-caprolactone), PCL. In this study, 3D scaffolds based on this polymer (PHMGCL, HMG:CL 8:92) were prepared by means of fiber deposition (melt-plotting). The biodegradation and tissue biocompatibility of PHMGCL and PCL scaffolds after subcutaneous implantation in Balb/c mice were investigated. At 4 and 12 weeks post implantation, the scaffolds were retrieved and evaluated for extent of degradation by measuring the residual weight of the scaffolds, thermal properties (DSC), and morphology (SEM) whereas the polymer was analyzed for both its composition ((1)H NMR) and molecular weight (GPC). The scaffolds with infiltrated tissues were harvested, fixed, stained and histologically analyzed. The in vitro enzymatic degradation of these scaffolds was also investigated in lipase solutions. It was shown that PHMGCL 3D-scaffolds lost more than 60% of their weight within 3 months of implantation while PCL scaffolds showed no weight loss in this time frame. The molecular weight (M(w)) of PHMGCL decreased from 46.9 kDa before implantation to 23.2 kDa after 3 months of implantation, while the molecular weight of PCL was unchanged in this period. (1)H NMR analysis showed that the degradation of PHMGCL was characterized by a loss of HMG units. In vitro enzymatic degradation showed that PHMGCL scaffolds were degraded within 50 h, while the degradation time for PCL scaffolds of similar structure was 72 h. A normal foreign body response to both scaffold types characterized by the presence of macrophages, lymphocytes, and fibrosis was observed with a more rapid onset in PHMGCL scaffolds. The extent of tissue-scaffold interactions as well as vascularization was shown to be higher for PHMGCL scaffolds compared to PCL ones. Therefore, the fast degradable PHMGCL which showed good biocompatibility is a promising biomaterial for tissue engineering applications.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3508 TB Utrecht, The Netherlands.
authors.forename: Hajar
authors.initials: H
authors.lastname: Seyednejad
authors.forename: Debby
authors.initials: D
authors.lastname: Gawlitta
authors.forename: Raoul V
authors.initials: RV
authors.lastname: Kuiper
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
authors.forename: Tina
authors.initials: T
authors.lastname: Vermonden
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001673:Biodegradation, Environmental / Q000187:drug effects; D005260:Female; D006900:Hydroxylation / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D008049:Lipase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*; D016062:Porosity / Q000187:drug effects; D019919:Prosthesis Implantation; D040521:Subcutaneous Tissue / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000199:Actins; D001672:Biocompatible Materials; D011091:Polyesters; C544013:alpha-smooth muscle actin, mouse; C016240:polycaprolactone; D008049:Lipase