Download PROJECT BRIEFS – POST DOCTORAL FELLOWSHIP APPLICATION

PROJECT BRIEFS – POST DOCTORAL FELLOWSHIP APPLICATION
– January 2017
NRC Biomaterials and Drug Delivery
Project 1:
Development of bio-inspired marine eel fish mucus derived hydrogel scaffolds for
cartilage tissue engineering
Duration: 24 months
Research Proposal Abstract
Moray eels are very common around Mauritius and the Seychelles. Morays cover their body surface by
protective mucus made up of glycoprotein called mucin to maintain smooth and scale less skin. They
have much thicker skin and high densities of goblet cells in the epidermis that allows mucus to be
produced at a higher rate than in other species. Mucus has regenerative capacity and helps to heal the
wounds when attacked by predators. A special class of glycoproteins and proteoglycans, is a main
component in hyaline cartilage. Its biomechanical role is to provide compressive properties to the tissue.
When cartilage is damaged as a result of traumatic rupture, patients experience severe pain as bones begin
to grind against each other. Further, there are several diseases associated with cartilage that includes
osteoarthritis, poly-chondritis, such pathological conditions can lead to loss and dysfunction of cartilage
tissue over time.
This research proposal aims at developing a less expensive bio-inspired hydrogel scaffold from fish
mucus gel. The glycoprotein rich mucus gel, may easily mimic cartilage tissue and help to repair and
reconstruction of cartilage tissues. The fish mucus derived hydrogel may act as excellent bioactive
interface while promoting tissue regeneration. The present investigation is designed to apply a threedimensional (3D) biomimetic hydrogel scaffold culture platform to systematically examine cartilage
regeneration potential of cartilage precursors and chondrocytes.
In addition, the FM hydrogel (Fish Mucus Hydrogel) could be potential cell delivery systems for cartilage
repair in vivo. The specific objectives of this proposal are to:
 Collect and purify the fish mucus from marine eel fish to prepare the hydrogel scaffold.
 Characterize the FM hydrogel by scanning electron microscopy for porosity, elasticity, swelling
ratio, electrical conductivity and rational degradable time that creates a suitable environment for
the regeneration of cartilage.
 To determine the cytotoxicity and biocompatibility of FM hydrogel scaffolds at in-vivo level.
 To study the effect of FM hydrogel scaffold on cartilage cell proliferation toward regeneration of
tissue using gene and protein expression studies.
 To implant the FM hydrogel scaffold into full-thickness cartilage defect in a rabbit model to
evaluate the regeneration of cartilage tissue.
Research work related to preparation of hydrogel scaffold and characterization will be conducted at
CBBR. All in vivo testing will be carried out at an Indian institution.
PROJECT BRIEFS – POST DOCTORAL FELLOWSHIP APPLICATION
– January 2017
NRC Biomaterials and Drug Delivery
Project 2:
Assessing the in vitro and in vivo efficacy of multiple anti-cancer loaded nanomicelles
and nanovesicles on breast cancer/obesity and pancreatic cancer mice models
Duration: 24 months
Research Proposal Abstract
Breast cancer is increasingly affecting women in Mauritius. While surgery and breast ablation remains the
major practice in Mauritius, new emerging nanochemotherapy treatment worldwide offers some hope to
patients for some type of breast cancer. Obesity has been associated with increased incidence and
mortality of breast cancer. While the precise correlation between obesity and breast cancer remains to be
determined, recent studies suggest that adipose tissue and adipose stem cells influence breast cancer
tumorigenesis and tumor progression. At present, seven ongoing randomized trials are evaluating the
influence of weight loss interventions on cancer end points (five in breast cancer, one in ovarian cancer,
and one in endometrial cancer). Pancreatic ductal adenocarcinoma (PDAC) is fatal with poor prognosis
and a median survival rate of 4-6 months and a 1-year survival rate of around 18% for all stages of the
disease. The PDAC problematic is centered on the fact that it is one of the most stroma-rich cancers with
a majority of the tumor volume consisting of the stroma/desmoplastic reaction to the cancer. This renders
PDAC resistant to chemotherapy. Combination of 5-fluorouracil (5-FU), leucovorin, irinotecan
hydrochloride and oxaliplatin (FOLFIRINOX) proved superior but at the cost of substantial toxicity. The
use of nanodrug delivery has been identified as a new avenue for PDAC cure as it could help overcome
the dense stromal barrier and increase drug bioavailability at the tumour site.
Nanotherapeutics could offer enhanced benefits over conventional chemotherapy and opens up new
perspectives for research and innovation. Recently Nab-Paclitaxel-Gemcitabine combination has been
approved for patients with metastatic pancreatic cancer with reduced toxicity and improved survival rate.
Nab-Paclitaxel is a nanoformulation using albumin to encapsulate the anti-cancer drug paclitaxel. We
have developed in-house nanocarriers and demonstrated their safety. These nanocarriers can encapsulate a
range of drugs either singly or in dual combination. CBBR has developed expertise in the combination of
drugs/bioactive molecules into nanoparticles that shows enhanced efficacy at in vitro level.
The proposed research aims at:
(i) optimizing the nanoformulations developed so far.
(ii) moving a step further into animal studies to test the efficacy of drug-loaded nanoparticles for cancer
treatment.
All nanoparticle synthesis and their drug loading will be done at CBBR. In vitro studies will be carried
out at CBBR. Animal studies will be conducted at the Centre for Nanotechnology and Advanced
Biomaterials (CeNTAB) in India and will be funded under the Research Collaborative Agreement
between MRC and CeNTAB. All prior Ethics Committee approval will be sought by CeNTAB before
engaging into animal studies.
PROJECT BRIEFS – POST DOCTORAL FELLOWSHIP APPLICATION
– January 2017
NRC Biomaterials and Drug Delivery
Project 3:
Assessment of the in vivo (mice model) performance of electrospun PHBV copolymer
or PHBV-natural polymer blends for skin tissue engineering and bone tissue engineering.
Duration: 24 months
Research Proposal Abstract
Skin tissue engineering for wound healing requires a biomimetic scaffold that provides a physical,
chemical, and biological environment to guide cells toward regeneration. The nanofibrous architecture
provided by electrospun scaffolds, as well as the ability to tailor their surface chemistry and offer
controlled delivery of bioactive agents, makes them a promising candidate for skin replacements. A range
of success in skin regeneration has been shown in vitro and in vivo in animal models using electrospun
scaffolds. Most animal trials have shown accelerated wound healing compared to negative controls or
commercially available treatments. This is true despite a range of structural, chemical, and biological
properties of the scaffolds. However, a closer look reveals that not all scaffolds performed equally in
terms of the biology of the regenerated tissue. The biological indicators of complete and proper wound
healing included control of collagen synthesis (type I and type III), minimal wound contraction, complete
re-epithelialization, vascularization, and formation of appendanges including hair follicles and sweat
glands. Successful skin tissue engineering requires a combination of appropriate materials, mechanical
properties, structure, and biological stimuli.
The Centre for Nanotechnology and Advanced Biomaterials (CeNTAB) in India has developed
nanoscaffolds based on polyhydroxybutyrate (PHB) or poly(hydroxybutyrate-co-valerate) (PHBV) for
skin regeneration in the presence of biological stimuli such as angiogenic growth factors. The Centre for
Biomedical and Biomaterials Research (CBBR) has developed nanoscaffolds which combine biosynthetic polymers (such as PHB or PHBV) or synthetic polymers such as polydioxanone/polymethyl
dioxanone with locally available natural polymers and has shown their in vitro efficacy towards fibroblast
cells and osteoblast cells.
The proposed research aims at moving a step further into animal studies to:
(i) test the efficacy of nanoscaffolds engineered under the NRC program for skin regeneration on mice
model. This research addresses the important problem of wound healing particularly in diabetic patients
where wounds remain in a prolonged state of inflammation. A first series of tests on mice will compare
the efficacy of the acellular scaffold alone (without cells) against a control with no scaffold. The next
series of tests will investigate the efficacy of wound healing on mice with a cell-seeded scaffold with and
without biological stimuli such as growth factors.
(ii) test the efficacy of the scaffolds for bone regeneration. Nanoscaffolds based on synthetic and natural
polymers developed at CBBR has proved to be quite interesting here too in enhancing biomineralization
and osteoblast growth.
All scaffolds will be prepared at CBBR. Animal studies will be conducted at CeNTAB and will be funded
under the Research Collaborative Agreement between MRC and CeNTAB. All prior Ethics Committee
approval will be sought by CeNTAB before engaging into animal studies.