Study Of Novel Reactive Polyurethanes For Bone Repair

Biomedical polyurethane has been used for treatment of bone defects since the late1950s because of its good biocompatibility, biodegradability, mechanical propertity andprocessability. However, since traditional biomedical polyurethane lacks biologicalactivity and cannot induce tissue regeneration or reconstruction in vitro or inimplantation sites, it is generally used as a carrier or support material. Physicalcomposites with active substances such as hydroxyapatite, collagen, mechanogrowthfactor (MGF), bone morphogenetic protein (BMP), can provide a certain biologicalactivity, but the active substance is released quickly so that the biological activity cannotlast for a long time. Chemical grafting is able to overcome the shortcomings of thephysical composites. Unfortunately, a serious drawback of the traditional polyurethanesis that they have no reactive groups for the chemical grafting.The purpose of this study is to design and synthesize a series of novel reactivepolyurethanes containg reactive carboxyl groups (PU-COOH_n) potentially used for bonerepair. PU-COOH_npolymers were synthesized by using a macrodiol based onpoly(DL-lactic acid) and polyethylene glycol (PDLLA-PEG400-PDLLA) as the softsegment, hexamethylene diisocyanate (HDI) as a coupling agent,2’2-dihydroxy methylpropionate (DMPA) and piperazine (PPZ) as chain extenders. ThePDLLA-PEG400-PDLLA was chosen because of its biocompatibility and highmechanical strength; HDI was used instead of aromatic isocyanates to avoid potentialcarcinogenicity; DMPA can provide reactive carboxyl groups for PU-COOH_n; PPZ wasemployed since it has been proved to improve mechanical property of PU polymers.The chemical structures and physical properties of PU-COOH_nwere characterized bymeans of FTIR, NMR, XPS and some conventional chemical analysis methods. Inaddition, the mechanical and thermal properties, hydrophilicity/hydrophobility, andshape memory properties were investigated by using tensile tests, DMA, TGA, staticwater contact angle and water uptake. Finally, the cytocompatibility of PU-COOH_npolymers was evaluated. The main research contents and conlusions were summarizedas follows:1. A series of PU-COOH_nwith different carboxyl contents were synthesized fromPDLLA-PEG400-PDLLA, HDI, DMPA, and PPZ. The molar ratios of DMPA toPDLLA-PEG400-PDLLA were varied from0.1to0.3to change carboxyl contents in PU-COOH_npolymers.①FTIR, NMR, XPS results revealed that PU-COOH_npolymers have beensuccessfully synthesized.②GPC-MALLs analysis indicated that Mnof PU-COOH_nwas slightly decreasedfrom33900to21500with the increase of DMPA from0.1to0.3.③The result from Rodamine method indicated that the carboxyl contents inPU-COOH_n were0.75wt%,0.78wt%, and0.86wt%, respectively with the increase ofDMPA from0.1to0.3.④The DSC analysis indicated that the Tgdecreased from28.5℃to26.7℃.2. The mechanical properties, shape memory properties, hydrophilic andthermostability of PU-COOH_nwere characterized by mechanical tensile test, DMA,static water contact angle, water absorption and TGA.①The hydrophilicity of PU-COOH_nwas enhanced with the increasing ofcarboxyl contents.②With the increase of DMPA from0.1to0.3, all the PU-COOH_npolymersshown good mechanical properties, and their young modulus, tensile modulus,elongation at break were668.75MPa/36.38MPa/287.18%、570.68MPa/38.75MPa/366.68%、523.40MPa/28.63MPa/301.58%, respectively.③The shape fixtion ratio and recovery ratio of all PU-COOH_npolymers weregreater than90%, demonstrating a good shape memory. The increase of hard segmentcontent raised the shape fixtion ratio while decreased the recovery ratio of PU-COOH_n.④The initial decomposition temperature of PU-COOH_nincreased from254.7℃to265.7℃and the maximum weight loss ratio reduced from99.8%to95.9%whenDMPA increased from0.1to0.3.3. The cytocompatibility of PU-COOH_nwas evaluated by investigating thecytotoxicity, adhesion and proliferation of osteoblasts, and the morphology and TNF-α,IL-1β and NO secretions of macrophages.①The toxicity levels of PU-COOH_npolymers were all fall in level0and1, whichmeans that the cytotoxicity of PU-COOH_npolymers can meet the ISO requirements forbiomedical materials.②Reduced osteobalst adhesion and proliferation, and enhanced inflammatoryresponses were observed with the increase of carboxyl contents in PU-COOH_n.