Mussel Mimetic Bioadhesive

Bioadhesives have attracted great attention as novel biomaterials due to their excellent adhesion, good biocompatibility and product diversification. Nowadays, they can replace the traditional suturing techniques and are widely used in the biomedical field. However, photopolymerization technology applied to the bioadhesives is novel research areas, which are few reports about this.Most artificial adhesives are difficult to form strong adhesion strength with matrix due to presence of humidity or body fluid, or cannot be as an ideal biomaterial because of their biotoxicity. Therefore, it is highly urgent and desirable to prepare a novel kind of bioadhesive with water-resistance adhesion and biocompatibility. Mussels are well known for their superior adhesion strength, excellent adhesion diversity, and non-immunogenicity. Nonetheless, their applications were limited by complex technology, low production and high cost through direct extraction or DNA recombinant technique. Poly(ethylene glycol)(PEG) is used in biomedical and pharmaceutical applications because of its superior hydrophilicity, good biocompatibility and no toxicity.This research was presented to prepare a kind of bioadhesive inspired by mussel through photopolymerizaiton, choosing multi-armed PEG as matrix, dopamine as object of study. The main conclusions were described as follows:1-. The photocrosslinkable PEG-triacrylate (PEG-TA) were prepared by esterification reaction, and their chemical structure was confirmed by RT-IR,1H-NMR.PEG-TA has good photopolymerizaiton property. The max conversion rate of acrylate double bonds of PEG-TA was more than90%. The swelling rate of PEG-TA had a linear relation with time and belonged to Fickian (Case I) diffusion model. PEG-TA (1500) reached swelling equilibrium within50min at37℃, and its equilibrium swelling ratio was158.41%. PEG-TA (20,000) was1308.3%and equilibrium appeared within6h. This kind of materials has excellent cell attachment and low cytotoxicity.2、Photocurable multifunctional PEG-dopamine (PEG-Dopas) was synthesized by using Michael addition reaction. Their chemical structure was confirmed by RT-IR,1H-NMR.There were obvious absorb peaks at λ=280nm of PEG-Dopas. Taken different preparation conditions, the dopamine content of PEG-Dopas distinctly changed. According to the standard absorption curve of dopamine hydrochloride in UV-Vis spectra, the dopamine content of samples could be calculated. The swelling rate of PEG-Dopas was Fickian (Case I) diffusion model. The equilibrium swelling ratio of PEG-Dopas (1500) and PEG-Dopas (20000) at PBS solution (pH7.4) were167.23%and1716.3%, respectively. The adhesive strength of PEG-Dopas (1500) was improved from0.89MPa to2.38MPa with the increase of the adhesive time from Oh to72h, and the adhesive strength of PEG-Dopas (20,000) was improved from0.34MPa to1.92MPa in the same time interval. The humid-resistant adhesion strength of PEG-Dopas (1500) was just slightly decreased less than0.01Mpa from Omin to60min. The bonding strength of PEG-TA without dopamine was tested for comparison purpose, and it was decreased obviously, which was too small to measure after60min. Average adhesion strength value of rat skin was0.05MPa. L929cells were not only attached well on the surface of PEG-Dopas but also showed the long spindle morphology which was typical of live fibroblastic cells and normal cell nucleus morphology characteristic. The results suggested that good cell viability on the PEG-Dopas gels. Results of the implantation experiment show that samples implanted were no toxic reaction for Wister rat. Pathologic observation was taken to found that there was no immunological reaction and only had short-lived snonspecific foreign body reaction in tissue around the gels. The implanted gels had good biocompatibility.3、Preparation four-armed PEG-Dopamine (qPEG-Dopas)(3000) based on the four-armed PEG. The performance of qPEG-Dopas (3000) and three-armed PEG-Dopamine (tPEG-Dopas)(3000) were compared.The max conversion rate of PEG-Quartacrylate (PEG-QA)(3000) was lower than that of PEG-Triacrylate PEG-TA(3000). Both their eventual conversion of acrylate double bonds was90%. Compared to the tPEG-Dopas (3000), the max conversion rate and eventual conversion of qPEG-Dopas (3000) was lower due to containing more content of catechol group. The equilibrium swelling ratio of PEG-QA, qPEG-Dopas were lower than that of PEG-TA and tPEG-Dopas, respectively. The adhesive strength of qPEG-Dopas was improved from0.86MPa to2.31MPa with the adhesive time from0h to72h, from0.59MPa to2.15MPa of tPEG-Dopas. After15min of UV exposur, adhesion strength of qPEG-Dopas bonding1.80mm pocrin skins was0.05MPa, and that of tPEG-Dopas was0.04MP; in addition, adhesion strength of them bonding1,20mm pocrin skins both were0.02MPa. There were lots of holes on the surface of qPEG-Dopas, but not found on PEG-QA. qPEG-Dopas were less cytotoxicity toward L929cell and had biocompatibalility. There were no inflammation, abscess and necrosis in subcutaneous tissue of Wister rat. The growth of pore, hair follicles and muscle tissue was normal. The trace amounts of macrophage were existed sporadically, which was common non-specific foreign body reaction.4、The Dopamine acrylate (DAm) and Dopamine methacrylate acid isopropyl amide (Dopa-GMA) were synthesized.DAm and Dopa-GMA had inhibition and retardation effect to photopolymerization. Particularly, the retardation effect of Dopa-GMA was obvious in the early stage. This result was opposite with our thought which bioadhesives had rapid photopolymerization. Therfore, DAm was chosen as object of our next study.5、The terpolymers which consisted of PEG-TA(1500), DAm, and NIPAAm with different molar ratio (NIPAAm-to-DAM) were prepared.Copolymer of DAm and NIPAAm had inhibition and retardation effect to photopolymerization. In addition, the conversion of the gels was obviously decreased at higher DAM concentrations. High molecular weight PEG-TA which added into the system led to the the conversion of C=C double bond increased within the same time. The swelling ratio of terpolymer was increased with increase of the NIPAAm-to-DAm molar ratio. Simultaneously, the equilibrium swelling ratio of samples at25℃was larger than that at37℃, the swelling equilibrium time at25℃was longer than at37℃. The adhesion strength of terpolymer were increased with increase of the DAm content. With increasing proportion of DAm content, the cross-link density (px) and the peak maximum of the Tg increased systematically. The cross-link density (px) was from0.25to0.48(×10-3mol/cm3). The results of MTT assays and cell attachment showed that terpolymer were biocompatible and less cytotoxicity towards the growth of L929cells. These terpolymer systems could be as a bioadhesive and applied to the biomedical field.