Technical NoteIn situ pore formation in a polymer matrix by differential polymer degradation
Introduction
The introduction of porosity in a polymer matrix has important consequences for drug delivery and tissue engineering [1]. Several approaches have been developed to introduce porosity in a polymer matrix namely, hydrocarbon templating [2], salt leaching [3], [4], gas expansion [5], sintering [4], freeze drying [6], and free form fabrication techniques e.g., three-dimensional polymer printing [7]. All these methods strive to introduce porosity ex vivo to facilitate cell seeding and subsequent tissue development either in vitro or in vivo. However, for certain applications such as synthetic bone grafts controlled pore formation in vivo with specific tissue ingrowth could be beneficial. We present herein a potentially new paradigm for the formation of pores in a polymer matrix in situ. This approach exploits the differences in polymer properties such as molecular weight, hydrophilicity (hydrophobicity), degradation and thermal behavior (e.g., glass transition temperature) to induce preferential degradation of one phase in a biphasic polymer system. In the present study this approach has been examined in vitro using poly(α-hydroxy acids) and poly(anhydrides). As examples two different biphasic polymer systems were evaluated namely: (a) PLGA (minor phase) dispersed in a poly(anhydride) (PA) major phase and, (b) PA (minor phase) dispersed in a PA (major phase). In the former case, the differences in polymer degradation characteristics (bulk vs. surface erosion) was exploited i.e., the PLGA is expected to undergo bulk erosion and the PA surface erosion [8]. In the later case, differences in the hydrophobicity of polymers that exhibit similar erosion behavior were exploited.
Section snippets
Materials
Poly(d,l-lactic-co-glycolic acid) (P(dl)LGA, 50:50, RG502, MW 20,000, polydispersity of ∼1.5) was purchased from Boehringer Ingelheim (Indianapolis, Indiana) and used as received. Poly(anhydrides) namely: poly(bis(p-carboxy-phenoxy-propane)-co-sebacic acid) (p(CPP:SA) in molar ratio 20:80 (MW 100,000) and 80:20 (MW, ∼20,000) were synthesized as described elsewhere [9]. In addition to MW determination by gel permeation chromatography the polymer was characterized using IR, proton-NMR and
Results
The average size of the polymer microspheres was 40 μm in both the PLGA and the PA system. SEM images of the cross-section of p(CPP:SA) (80:20) wafers containing 0–75 w/w% of PLGA microspheres after 4 weeks of degradation are shown in Figs. 1A–F. A cross-section of p(CPP:SA) (80:20) containing no microspheres after 4 weeks degradation is shown in Fig. 1A. It was observed that after 4 weeks, the polymer matrix without the microspheres had undergone minimal degradation and was devoid of any pores.
Discussion
An approach to the creation of porosity in a matrix via preferential removal of a polymer phase (porogen, minor phase) as described herein is shown in Scheme 1. This approach, while being a variant of the hydrocarbon templating and salt leaching methods, differs from them in the following aspects. (1) The porogen, which is also the minor phase in a biphasic polymer system is a degradable polymer and, (2) the porosity is introduced in situ by the hydrolysis of this pore forming minor phase. The
Acknowledgments
The authors would like to thank Dr. Benjamin Wu for his assistance in obtaining the SEM images. This work was supported in part by a grant form the National Institutes of Health (R24-AI477 39-03) to VPS and R.
References (12)
- et al.
Preparation and characterization of poly(l-lactic acid) foams
Polymer
(1994) - et al.
Novel approach to fabricate porous sponges of poly(d,l-Lactic-co-glycolic acid) without the use of organic solvents
Biomaterials
(1996) Solid free form fabrication of drug delivery devices
J Controlled Rel
(1996)- et al.
Tissue engineering
Science
(1993) - et al.
Macroporous polymeric solids by hydrocarbon templating
Proc Natl Acad Sci USA
(2000) - et al.
Fabrication of biodegradable polymer scaffolds to engineer trabecular bone
J Biomat Sci Polym Ed
(1995)
Cited by (0)
- 1
Present address: Faculty of Pharmacy, University of Montreal, Montreal, H3C-3J7, Canada.