title: Improved biocompatibility of poly(lactic-co-glycolic acid) orv and poly-L-lactic acid blended with nanoparticulate amorphous calcium phosphate in vascular stent applications.
abstract: Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Zheng
authors.forename: Yujue
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Lan
authors.forename: Yongnan
authors.initials: Y
authors.lastname: Lyu
authors.forename: Gaoke
authors.initials: G
authors.lastname: Feng
authors.forename: Yipei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shizu
authors.initials: S
authors.lastname: Tagusari
authors.forename: Edward
authors.initials: E
authors.lastname: Kislauskis
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.forename: Stephen
authors.initials: S
authors.lastname: McCarthy
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
authors.forename: Roger
authors.initials: R
authors.lastname: Laham
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
authors.forename: Wei Wang
authors.initials: WW
authors.lastname: Gu
authors.forename: Tim
authors.initials: T
authors.lastname: Wu
mesh_terms: D020341:Absorbable Implants / Q000009:adverse effects*; D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D002130:Calcium Phosphates / Q000009:adverse effects* / Q000737:chemistry; D019344:Lactic Acid / Q000009:adverse effects* / Q000737:chemistry; D008297:Male; D058729:Peripheral Arterial Disease / Q000209:etiology* / Q000473:pathology; D011091:Polyesters; D011100:Polyglycolic Acid / Q000009:adverse effects* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000009:adverse effects*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015607:Stents / Q000009:adverse effects*
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); C020243:calcium phosphate