Reduction of Inflammatory Reaction of Poly(D,L-Lactic-Co-Glycolic Acid) Using Demineralized Bone Particles

Abstract

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.

Thrombotic responses to coronary stents, bioresorbable scaffolds and the Kounis hypersensitivity-associated acute thrombotic syndrome

“…Specifically, during poly-L-lactic-acid (L-lactic-coglycolic acid) degradation, acidic degradation products such as lactic and glycolic acid accumulate and decrease the pH in the surrounding tissue. This can trigger inflammatory and foreign body reactions in vivo (55,56). Indeed, local foreign-body reactions (57), synovitis (58) especially in orthopedics and hypersensitivity reactions (59) have been associated with the use of poly (D,L-lactic-co-glycolic) acid.…”

Recent Advances in Biodegradable Metals for Medical Sutures: A Critical Review

“…Later on, the development of discharging sinuses and severe osteoarthritis could be observed. Debris of PLGA (black arrows in Figure 1 B) massively attracted macrophages and multinucleated giant cells (white arrows in Figure 1 B) and lead to the formation of a foreign body granuloma in a study by Yoon et al [ 105 ] Within a study by Onuki et al [ 106 ] multiple foreign body responses to PVA/PLGA microsphere composites (asterisk in Figure 1 The different effects on the surrounding tissue from different polymers was described in studies by Van der Giessen et al [ 27 ] and Tsuji et al [ 107 ] Van der Giessen et al [ 27 ] investigated the tissue response of fi ve different polymers (PGLA, PCL, PHBV, POE and PEO/PBTP) in coronary arteries of pigs. At four weeks post-surgery, they found distinct infl ammatory reactions in the tissue surrounding the polymer, along with signs of aneurysms and necrosis.…”

“…Reprinted with permission. [ 105 ] Copyright 2008, Mary Ann Liebert, Inc. C) Formation of mixed infl ammatory cells (black arrow) and zones of mineralization (yellow box) around degrading PVA/PLGA microsphere composites (asterisk) 60 days after implantation in subcutaneous tissue. Reprinted with permission .…”

Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine

“…71 A similar reduction in the degree of fibrous tissue formation around PLGA scaffold implants was observed when aciddemineralized bone particles were embedded in scaffolds designed for bone tissue regeneration. 72 These demineralized bone particles are known to contain a complex collection of proteins, including matrix collagen, bone morphogenetic protein, and other factors, and the precise signals from these particles involved in mitigating fibrous tissue formation in this instance remain unknown. In a more targeted strategy, van Putten et al impregnated cross-linked collagen scaffolds with recombinant IL-10, one of the key cytokines involved in arresting inflammatory responses, which directly acts on macrophages, dendritic cells, and T cells.…”