Reduction of inflammatory reaction of poly(d,l-lactic-co-glycolic Acid) using demineralized bone particles.
Poly(lactide-co-glycolic acid) (PLGA) has been widely applied to tissue engineering as a good biocompatible material because of its biodegradability and nontoxic metabolites, but how the inflammatory reaction of PLGA on the surrounding tissue in vivo is reduced has not been discussed sufficiently. We hypothesized that the cells neighboring the PLGA implant might have an inflammatory response that could be reduced by impregnating demineralized bone particles (DBPs) into the PLGA. We manufactured five different ratios of DBP/PLGA hybrid materials, with each material containing 0, 10, 20, 40, and 80 wt% of DBPs of PLGA. For biocompatibility test, NIH/3T3 mouse fibroblasts were cultured on the DBP/PLGA scaffold for 3 days. The inflammatory potential of PLGA was evaluated using messenger ribonucleic acid expression of tumor necrosis factor alpha (TNF-alpha) and interleukin 1-beta (IL-1beta) on a human acute promyelocytic leukemic cell (HL-60). The in vivo response of DBP/PLGA film was compared with that of PLGA film implanted subcutaneously; the local inflammatory response was observed according to histology. The DBP/PLGA scaffold had no adverse effect on NIH/3T3 initial cell attachment and did not affect cell viability. DBP/PLGA films, especially PLGA films containing 80% DBP, elicited a significantly lower expression of IL-1beta and TNF-alpha from HL-60 cells than PLGA film alone. In vivo, DBP/PLGA film demonstrated a more favorable tissue response profile than PLGA film, with significantly less inflammation and fibrous capsule formation as below only 20% of DBP in PLGA film during implantation. This study shows that application of DBPs reduces the fibrous tissue encapsulation and foreign body giant cell response that commonly occurs at the interface of PLGA.
Yoon
Sun Jung
SJ
BK-21 Polymer BIN Fusion Research Team, Chonbuk National University, Jeonju, Korea.
Kim
Soon Hee
SH
Ha
Hyun Jung
HJ
Ko
Youn Kyung
YK
So
Jung Won
JW
Kim
Moon Suk
MS
Yang
Young Il
YI
Khang
Gilson
G
Rhee
John M
JM
Lee
Hai Bang
HB
D000210:Acute-Phase Reaction / Q000276:immunology*; D000818:Animals; D018775:Bone Demineralization Technique; D002478:Cells, Cultured; D005355:Fibrosis / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D015743:Giant Cells, Foreign-Body / Q000166:cytology; D006016:Glycolates / Q000276:immunology*; D018922:HL-60 Cells; D006801:Humans; D020007:Implants, Experimental; D053583:Interleukin-1beta / Q000235:genetics; D019344:Lactic Acid; D008264:Macrophages / Q000166:cytology; D008422:Materials Testing; D051379:Mice; D041681:NIH 3T3 Cells; D020556:Neutrophil Infiltration; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D040521:Subcutaneous Tissue; D054457:Tissue Scaffolds; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D006016:Glycolates; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid