Introduction: Previously we have reported studies in a polymer blend consisting of 60 wt.% of Poly(lactide-co-glicolide) (PLGA) and 40 wt.% of natural rubber (NR) obtained from hevea brasiliensis’ latex[1],[2]. A cranial expansion spring was produced and tested in vivo with this material, with successful results[3]. PLGA is a well-recognized resorbable polymer, while NR is little researched for biomedical applications, even being described as improving angiogenesis and wound healing, which has been reported as being consequence of hevea brasiliensis’ serum content[4]. In this work the synthesis method and preliminary characterization of a tri-component material composed of the already described polymer blend and dispersed hydroxyapatite (Hap) are presented. The developed route utilizes the NR in solution in a wet chemical in situ process for Hap synthesis. In a bone repair application the angiogenic characteristics of the natural rubber would provide improved vascularization while the gradual resorption of PLGA would ensure an increasing degree of porosity while continuously provide access to the hydroxyapatite particles.
Materials and Method: Composites consisting of PLGA, NR and Hap were produced in situ with the percentages of Hap of 0 wt.%, 10 wt.%, 20 wt.% and 30 wt.%. Highly concentrated solutions of NR in THF were prepared, followed by addition of 0.5 M solutions of Ca(NO3).4H2O and 0.3 M solutions of H3PO4, both in tetrahidrofuran (THF). During the entire process NH4OH was used to maintain a pH higher than 8 in the solution to ensure formation of hydroxyapatite as the only calcium phosphate phase. After aging under agitation for 24 hours, a PLGA solution in THF was added and the mixture was dried. The produced composite was washed in deionized water overnight. The same process of synthesis was performed in absence of NR for comparison, leading to a highly agglomerated product and impossibility of production of the composites.
Results and Discussion: Phase analysis by x-ray diffraction and fourier transform infrared confirmed hydroxyapatite as the only calcium phosphate phase present. Differential scanning calorimetry has shown incomplete miscibility between NRL and PLGA and no influence of Hap in thermal properties. Scanning electron microscopy was used to evaluate the degree of agglomeration of Hap particles in the polymer matrix, showing dispersed aggregates with different sizes.
Conclusions: The developed route successfully produces PLGA/NR/Hap composites in an in situ process. NR was crucial for particle dispersion, since the process performed in absence of polymer led to agglomeration of particles. The dispersion effect over Hap could be attributed to interaction with polymer chains, or latex biomolecules, or both, but further research is needed for confirmation.
CNPq - Brasil. CAPES - Brasil.
References:
[1] Faller, G.; dos Santos, L. A.; Marques, D.; Collares, M. V., Development and testing of an absorbable spring for cranial expansion in rabbits. Journal of Cranio-Maxillofacial Surgery 2015, 43 (7), 1269-1276.
[2] Marques, D. R. ; Santos, L.A. ; Schopf, L. F. ; FRAGA, J. C. S. . Analysis of Poly(Lactic-co-Glycolic Acid)/Poly(Isoprene) Polymeric Blend for Application as Biomaterial. Polímeros (São Carlos. Online), 2014, 579-584.
[3] Kim, J. H. ; Marques, D. R. ; Faller, G. J. ; Collares, M. V. M. ; Rodriguez, R. ; Santos, L.A.; Dias, D. S. . Experimental comparative study of the histotoxicity of poly(lactic-co-glycolic acid) copolymer and poly(lactic-co-glycolic acid)-poly(isoprene) blend. Polímeros (São Carlos. Online), 2014, 24, 529-535.
[4] Mendonça, R. J.; Maurício, V. B.; de Bortolli Teixeira, L.; Lachat, J. J.; Coutinho-Netto, J., Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis. Phytotherapy Research 2010, 24 (5), 764-768.