Debasish Mondal

Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges

ABSTRACT Recently, poly (є-caprolactone) (PCL) has gained a lot of attention, and shown great potential in biomedical applications. Among synthetic polymers, PCL is one of the easiest to process and manipulate into a large range of shapes and sizes due to its low melting temperature and its superior viscoelastic properties. In this review article the authors focus mainly on the properties of PCL-based biomaterials relevant to drug delivery and tissue engineering applications. The authors provide an insight into the recent developments and challenges of PCL-based biomaterials as a critical component of new therapeutic strategies for many diseases. GRAPHICAL ABSTRACT

Polycaprolactone-thiophene-conjugated carbon nanotube meshes as scaffolds for cardiac progenitor cells.

The myocardium is unable to regenerate itself after infarct, resulting in scarring and thinning of the heart wall. Our objective was to develop a patch to buttress and bypass the scarred area, while allowing regeneration by incorporated cardiac stem/progenitor cells (CPCs). Polycaprolactone (PCL) was fabricated as both sheets by solvent casting, and fibrous meshes by electrospinning, as potential patches, to determine the role of topology in proliferation and phenotypic changes to the CPCs. Thiophene-conjugated carbon nanotubes (T-CNTs) were incorporated to enhance the mechanical strength. We showed that freshly isolated CPCs from murine hearts neither attached nor spread on the PCL sheets, both with and without T-CNT. As electrospun meshes, however, both PCL and PCL/T-CNT supported CPC adhesion, proliferation, and differentiation. The incorporation of T-CNT into PCL resulted in a significant increase in mechanical strength but no morphological changes to the meshes. In turn, proliferation, but not differentiation, of CPCs into cardiomyocytes was enhanced in T-CNT containing meshes. We have shown that changing the topology of PCL, a known hydrophobic material, dramatically altered its properties, in this case, allowing CPCs to survive and differentiate. With further development, PCL/T-CNT meshes or similar patches may become a viable strategy to aid restoration of the postmyocardial infarction myocardium.

Controlled release of complexed DNA from polycaprolactone film: Comparison of lipoplex and polyplex release

This report investigates the comparative in vitro controlled release and transfection efficiencies of pDNA-lipofectamine complex (lipoplex) and pDNA-poly(ethylene imine) complex (polyplex), from a biodegradable polycaprolactone (PCL) film. The effect of molecular weight of gelatin used as a porogen on in vitro release and transfection efficiency was also studied. A sustained release profile was obtained for naked pDNA and lipoplex from polymeric films for a month, while the release of polyplexes (PEI/DNA) is simply a burst at day 5, with little or no release thereafter. The release of polyplexes from PCL films is retarded due to interaction between the polyplexes and the polymer. A high burst release was seen for naked pDNA which was suppressed in the presence of gelatin. The extent of suppression of the burst effect by gelatin increased with its molecular weight. For complexed pDNA (lipoplex), the release was slow, but could be accelerated using gelatin; again the acceleration in release is dependant on the molecular weight of the gelatin used. The addition of gelatin as a porogen has no effect on the release of polyplexes from PCL films. The bioactivity of released plasmid DNA and complexes was studied by in vitro transfection using COS-7 cells. Transfection was observed from released lipoplexes samples till day 9 from PCL film with lower MW gelatin and till day 18 in the case of PCL films with higher MW gelatin. The results also showed that the bioactivity of released lipoplexes was superior to that of the naked pDNA.

Functionalization of the Polymeric Surface with Bioceramic Nanoparticles via a Novel, Nonthermal Dip Coating Method

The only nonthermal method of depositing a bioceramic-based coating on polymeric substrates is by incubation in liquid, e.g., simulated body fluid to form an apatite-like layer. The drawbacks of this method include the long processing time, the production of low scratch resistant coating, and an end product that does not resemble the intended bioceramic composition. Techniques, such as plasma spraying and magnetron sputtering, involving high processing temperature are unsuitable for polymers, e.g., PMMA. Here, we introduce a nonthermal coating method to immobilize hydroxyapatite (HAp) and TiO2 nanoparticles on PMMA via a simple and fast dip coating method. Cavities that formed on the PMMA, induced by chloroform, appeared to trap the nanoparticles which accumulated to form layers of bioceramic coating only after 60 s. The resulting coating was hydrophilic and highly resistant to delamination. In the context of our research and to address the current clinical need, we demonstrate that the HAp-coated PMMA, which is intended to be used as a visual optic of a corneal prosthetic device, improves its bonding and biointegration with collagen, the main component of a corneal stroma. The HAp-coated PMMA resulted in better adhesion with the collagen than untreated PMMA in artificial tear fluid over 28 days. Human corneal stromal fibroblasts showed better attachment, viability, and proliferation rate on the HAp-coated PMMA than on untreated PMMA. This coating method is an innovative solution to immobilize various bioceramic nanoparticles on polymers and may be used in other biomedical implants.

Sustained release of complexed DNA from films: Study of bioactivity and intracellular tracking

Sustained DNA delivery from polymeric films provides a means for localized and prolonged gene therapy. However, in the case of bioactive molecules such as plasmid DNA (pDNA), there are limitations on the achievable release profiles as well as on the maintenance of bioactivity over time. In this report, the authors have investigated the bioactivity of the released DNA (naked and complexed with lipofectamine) from polymeric films using in vitro cell transfection of COS-7 cell lines. The polymeric system consists of a biodegradable semicrystalline polymer such as poly(ε-caprolactone) (PCL) with or without blended gelatin. Sustained release of lipoplexes and of pDNA is shown over several days. However, lipoplexes released from pure PCL films show no transfection on day 18, whereas lipoplexes released from PCL-gelatin films continue to transfect cells on day 18 of release. Confocal studies were used to determine the reasons for this difference in transfection efficiency, and it is proposed that association of the lipoplex with gelatin confers protection from degradation in the cytoplasm. The results also showed that the bioactivity of released lipoplexes was superior to that of the naked pDNA. For both naked pDNA and the lipoplexes, the presence of gelatin helped to maintain the bioactivity over several days.