title: Effects of lactic acid and glycolic acid on human osteoblasts: a way to understand PLGA involvement in PLGA/calcium phosphate composite failure.
abstract: The use of degradable composite materials in orthopedics remains a field of intense research due to their ability to support new bone formation and degrade in a controlled manner, broadening their use for orthopedic applications. Poly (lactide-co-glycolide) acid (PLGA), a degradable biopolymer, is now a popular material for different orthopedic applications and is proposed for use in tissue engineering scaffolds either alone or combined with bioactive ceramics. Interference screws composed of calcium phosphates and PLGA are readily available in the market. However, some reports highlight problems of screw migration or aseptic cyst formation following screw degradation. In order to understand these phenomena and to help to improve implant formulation, we have evaluated the effects of PLGA degradation products: lactic acid and glycolic acid on human osteoblasts in vitro. Cell proliferation, differentiation, and matrix mineralization, important for bone healing were studied. It was found that the toxicity of polymer degradation products under buffering conditions was limited to high concentrations. However, non-toxic concentrations led to a decrease in cell proliferation, rapid cell differentiation, and mineralization failure. Calcium, whilst stimulating cell proliferation was not able to overcome the negative effects of high concentrations of lactic and glycolic acids on osteoblasts. These effects help to explain recently reported clinical failures of calcium phosphate/PLGA composites, but further in vitro analyses are needed to mimic the dynamic situation which occurs in the body by, for example, culture of osteoblasts with materials that have been pre-degraded to different extents and thus be able to relate these findings to the degradation studies that have been performed previously.
authors: Orthopaedic Research Unit, University of Cambridge, Cambridge, United Kingdom. fmeyer@unistra.fr
authors: Florent
authors: F
authors: Meyer
authors: John
authors: J
authors: Wardale
authors: Serena
authors: S
authors: Best
authors: Ruth
authors: R
authors: Cameron
authors: Neil
authors: N
authors: Rushton
authors: Roger
authors: R
authors: Brooks
mesh_terms: D001672:Biocompatible Materials; D002130:Calcium Phosphates / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004359:Drug Therapy, Combination; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006016:Glycolates / Q000633:toxicity*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000633:toxicity*; D016348:Osseointegration; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011474:Prosthesis Design; D011475:Prosthesis Failure; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D016326:Extracellular Matrix Proteins; D006016:Glycolates; C493709:RUNX2 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; C031149:glycolic acid; D015675:Osteocalcin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C020243:calcium phosphate