Can seaweed heal wounds without scarring? | 91TV
Transcript
- Dr Nowsheen Goonoo: Thank you, Robin, for the kind introduction. So before diving into today's topic,
- I would like to take you briefly through the research centre, and about the research
- activities that we are currently looking at. So the Centre for Biomedical and Biomaterials
- Research, CBBR was created in 2011, and in December this year it will be marking its
- ten years of existence. The main research and innovation thrust of the research centre
- is on the design and engineering of smart materials from locally available resources.
- It is also highly engaged in building intellectual capital through the training of
- postdocs and postgraduate students. It also offers consultancy services to industry
- through analytical services, and also assist them in the uptake of nanotechnology.
- The head of the Centre for Biomedical and Biomaterials Research, CBBR is Professor
- Bhaw-Luximon, who holds a personal chair in biomaterials engineering and nanomedicine. The
- research at our centre is divided into three broad categories. So we have nanofibrous scaffolds,
- hydrogels for molecule and cell encapsulation, and nanoparticle synthesis. I lead all research
- activities which is related to nanofibrous scaffolds. We also have a number of MPhil PhD
- students and postgraduate students who are working on a full-time basis at our research centre.
- Now, let us move to the main topic of today's lecture, which is the use of nanoengineered
- seaweeds for the treatment of diabetic foot ulcers. Type 2 diabetes is a worldwide problem,
- and one of the most important complications of Type 2 diabetes is diabetic foot also.
- In Africa alone, there is 19.4 million people who suffer from Type 2 diabetes,
- and out of these 19.4 million people, 2.3 million of them suffer from diabetic foot ulcers.
- Now, diabetic foot ulcers are chronic wounds that occur in the lower extremity of the limbs,
- and they are very slow healing in nature. They can take months or even years to heal,
- and in most cases they do not heal at all, leading to amputations. It is estimated that 15 per cent
- of people who suffer from diabetic foot ulcer will experience an amputation because of the slow
- healing nature of diabetic foot ulcers, and also because of the fact that they lead to amputations.
- These kind of wounds, they add significantly to the economic burden of a country. In Africa alone,
- the total economic burden due to diabetic foot ulcer is estimated to be around $11 billion.
- Commercial products which are available to treat diabetic foot ulcers are very expensive
- and on average it costs around €1000 to treat a single diabetic foot ulcer.
- Therefore, this is not affordable for the African continent and there is an urgent need to develop
- cheap and affordable materials which could be used to treat diabetic foot ulcer in Africa.
- So what we are proposing is the use of nanoengineered seaweeds to treat diabetic
- foot ulcers. More specifically, we are proposing to use nanofibers in the form of blend fibres
- consisting of a seaweed derived polymer in combination with another biodegradable polymer
- to treat these types of chronic wounds.
- Now the concept of tissue engineering to regenerate skin is a fairly
- simple concept where we need raw materials, so the raw materials are the skin cells and the scaffold.
- The skin cells are then placed onto the scaffold, and then the cell seeded scaffold
- is placed in a bioreactor, where they have the appropriate condition for them to grow
- and eventually give rise to the new tissue, which in this case will be skin.
- Now in tissue engineering, the scaffold plays a crucial role, and in fact, it is the scaffold that
- will determine whether the tissue engineering process is going to be successful or not.
- In vivo or in the human body, the cells they are located in a very complex and
- dynamic microenvironment, which is known as the extracellular matrix. The cells,
- they are constantly communicating with each other, but also with extracellular matrix components.
- The extracellular matrix it's consist mainly of proteins such as collagen and elastin,
- but also consists of specialised proteins such as glycosaminoglycans.
- The seaweed based polymers that we are looking at, their structure resembles
- closely that of the glycosaminoglycans and therefore when we are using the seaweeds,
- we are able to trick the cells into thinking that they are in their native microenvironment.
- So in the first part of our study, we fabricated blend nanofibers consisting of a seaweed based
- polymer in combination with a biodegradable polymer, which in this case is Polydioxanone,
- which is here abbreviated as PDX. We were mainly concerned with two different types of seaweeds,
- namely red seaweeds and brown seaweeds. From the red seaweeds, we extracted the polymer kappa
- carrageenan, which will be abbreviated as KCG in the next slides, and from the brown seaweeds
- we extracted fucoidan, which is abbreviated as FUC. So we basically fabricated blend nanofibers
- consisting of PDX and KCG, or PDX in combination with fucoidan, and the ratio of PDX to the seaweed
- derived polysaccharides were varied such that we had a range of different compositions.
- The blend nanofibers were characterised in depth in terms of their physicochemical properties,
- and we can see from the images on the right hand side that all the fibres that were very smooth and
- there were no surface protrusions. Now if we look closely at the scanning electron microscope image
- shown on the lower right hand side, we note the presence of a second component for the fucoidan
- containing fibre. This is very likely due to the presence of fucoidan on the surface of the fibre.
- The wound healing cascade consists of three overlapping stages, namely the inflammatory phase,
- the proliferative phase, and the remodelling phase.
- In the inflammatory phase, we're going to have an increase in blood flow
- and macrophages are going to be activated and they're going to migrate to the
- site of the wound. After the inflammatory phase, we're going to have the proliferative phase where
- we're going to have proliferation and migration of fibroblasts to the wound site. At the same time,
- we're going to have proliferation of keratinocytes to the wound site, and this is going to be
- followed by migration of endothelial cells at the injury site. The last stage of the wound healing
- process we're going to have collagen synthesis and matrix reorganisation. At the same time we're
- going to have angiogenesis which is basically the formation of new blood vessels. Also fibroblasts
- are going to be involved, so as to reduce superficial contraction and scarring in the wound.
- We therefore try to investigate the potential of the fabricated scaffolds in each of the different
- phases in the wound healing cascade. So first of all, we looked at the inflammatory phase. So we
- seeded firstly mouse macrophages on the scaffolds, and we took scanning electron microscope images
- of the cells after 48 hours. The images shown on the left hand side indicate that as we increase
- the polysaccharide content, the cells, they became more flattened in shape, and also they
- became more smooth. We analysed the cell area of the macrophages on the different scaffolds, and we
- found that as we increase the biopolymer content, the cell area was also increasing irrespective of
- whether the polysaccharide was carrageenan or fucoidan. In the next step, we stained the cells
- in terms of their nucleus and cytoskeleton. So the image on the upper right hand side shows the
- fluorescence microscope image of the macrophage cells. In blue is the nucleus, and what is stained
- in green is the cytoskeleton of the cell. We try to quantify the actin edge intensity of the cells,
- and we noted that the actin edge intensity increased as we increased the biopolymer content.
- Overall, these results indicate that both kappa carrageenan and fucoidan addition to the scaffold
- favours the polarisation of macrophages to the M2 phenotype, which is basically the pro-healing or
- anti-inflammatory phenotype. We also tried to look at the behaviour of the scaffold
- in the proliferative phase by seeding fibroblast cells on the scaffold. We tried to quantify the
- number of cells that were growing on scaffolds after seven days using MTT assay, and the graph,
- which is shown on the left hand side, gives a summary of the results that were obtained.
- So overall we could conclude that the cells proliferated very well on all scaffolds, and
- they maintained good viability. This was in line with scanning electron microscope images, where
- we could see that the cells completely covered the surface of the scaffold after seven days.
- Another aspect which is very important in the proliferative phase is the migration of cells
- so as to close the wound. We therefore carried out in vitro wound scratch
- assay to look at the migration potential of fibroblasts using the seaweed derived scaffolds.
- The image on the right hand side basically shows how the wound was closing and how
- the cells were migrating into the in vitro wound site. We found that all
- the samples, therefore the positive control TCPS, the kappa carrageenan containing scaffold
- and fucoidan containing scaffold, they all favoured migration of cells into the wound area.
- If we look closely at the three images, we can see that the fucoidan containing scaffold promoted
- the migration of fibroblasts to a much higher extent compared to the remaining two samples.
- In the remodelling phase, a very important process which occurs is angiogenesis, which is basically
- the formation of new blood vessels. For any tissue or organ to be viable, we need to have
- a good supply of blood oxygen and nutrients and also removal of waste products.
- All this happens through a good blood vessel supply. Therefore, to look at whether the
- scaffolds were promoting angiogenesis, we seeded endothelial cells on the scaffold,
- and the graph on the lower left hand side indicate that the cells proliferated very well on all the
- scaffolds. The cell number remained practically the same on all the different scaffolds,
- irrespective of the biopolymer content and on the nature of the polysaccharide. The scanning
- electron microscope image was in line with the MTT results, where we noted a very high number
- of cells on all scaffolds. If we look closer at the scanning electron microscope image,
- we noted the presence of lumens in the scaffolds. Therefore, the cells were rearranging so as to
- form lumens, and this indicates the good angiogenic potential of the scaffolds.
- We also looked at whether the scaffolds could be used to grow and to support
- the growth of induced pluripotent stem cells. So briefly, we fabricated embryoid bodies
- consisting of around 2000 induced pluripotent stem cells. So as we can see from the optical
- image on the right hand side, we note that the embryoid bodies were very uniform in shape,
- and the average diameter of each of those embryoid bodies was around 343 micrometres.
- These embryoid bodies were then seeded onto the nanofibrous scaffold, and after 24 hours
- we performed live and dead staining on the cells to see whether the cells were still viable or not.
- These are the results that were obtained after the live and dead staining. So basically all the live
- cells are stained in green and the dead cells are stained in red. Therefore, we can conclude that
- most of the cells were viable on the scaffolds, and there were very few
- dead cells on the seaweed, containing seaweed derived polysaccharide based scaffolds.
- Because the scaffolds that we are fabricating are intended for human applications,
- we have to ensure that these scaffolds are non-toxic and biocompatible. Therefore,
- we carried out in vivo biocompatibility studies where the scaffolds were implanted in Wistar
- rats. So basically what we do is that we create subcutaneous pockets on the dorsal region of
- the rats, and then we implant three layers of scaffolds in each subcutaneous pockets.
- The three layers of scaffolds were labelled as exterior, middle, and interior. So the
- interior layer of the scaffold was the layer that was in contact with the muscle layer,
- and the exterior layer of scaffold was the layer that was in contact with the skin. The rats were
- then followed over a period of four weeks, and during that time period we looked for any signs
- of inflammation such as redness or swelling, and we also note the weight of the animal.
- At the end of the study, that is, at the end of four weeks, we took out the scaffolds and we
- analysed the scaffolds under the scanning electron microscope. We found that the all three layers of
- the scaffolds were completely covered with cells, and this therefore indicates that the cells could
- easily infiltrate in between the three different layers. We also took out a piece of the tissue
- at the subcutaneous pocket side, and we analysed it in terms of histological analysis.
- The image on the upper right hand side shows that for all three scaffolds, we had
- the presence of a fibrous capsule that was formed around the scaffolds. If we look closer,
- the thickness of the fibrous capsule varied depending on the nature of the scaffold.
- Therefore, if we look at the graph on the lower right hand side,
- we can see that the fucoidan containing scaffold led to a thinner fibrous capsule
- in comparison to the kappa carrageenan containing scaffold, or the pure PDX containing scaffold.
- Therefore, overall, we can say that the incorporation of fucoidan
- leads to better in vitro and in vivo cellular response compared to kappa carrageenan.
- In the second part of this study, we fabricated a second class of blend nanofiber's still consisting
- of seaweed derived polymers, but this time in combination with another biodegradable polymer,
- namely PHBV. Now PHBV stands for polyhydroxybutyrate valerate,
- and it is a special polymer because it has piezoelectric property.
- Now, a piezoelectric material is one that produces a voltage or a current when
- subjected to an external force. When cells are seeded on a scaffold in vitro,
- the cells are going to colonise the scaffold and the cells exert a mechanical
- force on the scaffold. This leads to micro deformations, which produces piezoelectricity.
- In the human body there are different tissues which are piezoelectric in nature. These include
- bone, cartilage, ligaments, and even skin. Therefore, we hypothesise that the use of
- a piezoelectric polymer in combination with a seaweed derived polysaccharides
- are going to further improve the wound healing process and accelerate the skin regeneration.
- Therefore, to test our hypothesis, we performed in vivo wound healing studies, where we compared
- the performance of different seaweed containing scaffolds, over different time periods. So the
- wound healing study was carried out over 21 days, and we took photos of how the wounds were closing
- over time for the different scaffold groups. So scaffold one corresponds to the negative control
- and scaffold two corresponds to the positive control. Now if we look closely at the first
- two scaffolds we see that the wounds did close after 21 days, but we had the formation of a scar.
- In comparison to the scaffold treated groups, we do not see the formation of scar
- at the end of the wound healing process. If we look even closely to scaffold five,
- we see that there is no scar formation at all right at the start of day 13.
- Now after the wound closed completely, we took out a small tissue at the wound site and we performed
- histological analysis. So the tissue was stained in terms of Masson's trichrome, and we quantified
- different parameters such as the epidermis thickness, the dermis thickness, the granulation
- tissue area, as well as the global healing index. In general, a high global healing index,
- together with a small granulation tissue area corresponds to good overall healing.
- Therefore, if we look closely at the table on the right hand side, we note that scaffold five led to
- the lowest granulation tissue area and the highest global healing index, which indicates that this
- scaffold led to the best performance. Scaffold five, if we look at the table here, scaffold
- five corresponded responded to PHBV fucoidan. Therefore, the scaffold contained fucoidan in
- combination with the piezoelectric polymer, which confirms our hypothesis that fucoidan
- when in combination with a piezoelectric polymer leads to better or accelerated wound closure.
- To conclude, we successfully fabricated blend nanofibers consisting of seaweed derived polymers,
- and we showed that these blend nanofibers could promote fibroblast migration and proliferation.
- They promoted the macrophage polarisation towards the M2 phenotype and also promoted endothelial
- cell proliferation, as well as supported the growth and proliferation of induced
- pluripotent stem cells. Most importantly, in vivo wound healing studies showed that
- there were no scar formation and also the blend fibres accelerated the wound healing process,
- in contrast to the negative control or to the remaining positive samples.
- Finally, I would like to thank the head of the research centre where I work at
- and also our research group leader, and also all colleagues who work at the same research centre.
- A special thanks to the funding agencies, in particular the University of Mauritius and the
- Mauritius Research and Innovation Council, the L'Oreal-UNESCO Foundation and the Alexander von
- Humboldt Foundation for funding my postdoctoral fellowship. Of course, a special thank you to,
- CYROI, who is our close collaborator for in vivo testing.
- Sir Robin Grimes: Thank you.
- Dr Goonoo, that was really very, very interesting indeed.
- It's a little way from my personal expertise, but I am particularly interested in some of the
- nanomaterials aspects. So I'm going to start by asking a question about the morphology
- of the scaffolds and the morphology of the blood vessels that form in the last stage
- of wound healing. Is there a relationship between those different morphologies?
- Dr Nowsheen Goonoo: Yes, so thank you for the question. It's a very good question. So firstly,
- let me answer the first part of the question, which is about the morphology of the scaffolds.
- So as you have seen in the talk, the oldest scaffolds, they are blend fibres, so they are
- nanofibers in nature. The reason why we chose the nanofibrous nature of scaffold is to be able to
- mimic the native microenvironment in which cells are located. So if we recall in one of the slides,
- we saw how the extracellular matrix look like, and we see that the cells they are surrounded
- with polymer fibres. So that's why we chose a scaffold which is fibrous in nature so as
- to be able to mimic closely the microenvironment in which cells are located. Now the nanofibers,
- they are also quite interesting in the sense that they offer, for example,
- a very easy way of modifying those fibres so as to attach functional groups to them so as to make
- them more biocompatible, for example. Also using the process of electrospinning to make nanofibers,
- we can choose a wide range of polymers so that we can convert them into nanofibers.
- Another interesting aspect of nanofibers is that they are 3D in nature, and they are also porous,
- which means that they can absorb wound exudates in the case of diabetic foot ulcers.
- The second part of the question about blood vessel formation, indeed, we do observe a
- difference in terms of how the endothelial cells behave on the different scaffolds. What we noted
- was that the endothelial cells, they preferred nanofibrous scaffolds with small fibre diameters.
- So far we have only looked at 2D cell cultures, therefore, cultures, culturing the cells on the
- scaffolds in terms of a 2D nature. We have not looked at how the cells were organising in terms,
- in three dimensions. This is something that we are planning to look at in the future,
- and I'm sure that we will have very interesting results with regards to the different types of
- polysaccharides and the rearrangement of the endothelial cells on the different scaffolds.
- Sir Robin Grimes: Okay, so from my perspective, again of not being an expert here.
- So this means that these scaffolds are bioactive as well as being biocompatible. Is that right?
- Dr Nowsheen Goonoo: Yes it's correct. So those polysaccharides that we used
- like kappa carrageenan and fucoidan, they possess some special functional groups on the backbone,
- which makes them biocompatible and also bioactive. Therefore,
- the cells like those functional groups and they proliferate very well on those scaffolds. So it
- resembles, in fact, the proteins which are found in the extracellular matrix.
- Sir Robin Grimes: Okay. Ah, I think I'm starting to understand. So if we were to come back in,
- say, three, four, five years' time after this process had been used, would the original scaffold
- material then have been reabsorbed, be absorbed by the body and replaced by completely new cells, or
- will that scaffold always be there?
- Dr Nowsheen Goonoo: No. So actually the scaffolds, all the scaffolds that we are
- looking at are biodegradable, which means that they will be absorbed away over time.
- So there is something which we look at which is very important is the biodegradation rate
- of the scaffold. So in the tissue regeneration process, for example,
- in this case we are looking at skin repair of diabetic foot ulcers. It's very important to match
- the biodegradation rate of the scaffold with that of skin tissue regeneration. Therefore
- what happens is that as the new tissue is being formed, the scaffold is slowly dissolving away,
- so that at the end of the wound closing process, there is no scaffold left at
- the wound site. So it's only the tissue which is formed, the new tissue formed, which is present.
- Sir Robin Grimes: Oh, wow. So that does that mean that looking again ten years' time or something,
- that different people will get slightly different scaffolds to match their body types,
- or the way their bodies behave. Is that possible?
- Dr Nowsheen Goonoo: It actually doesn't really depend on the individual, but it depends on
- the tissue that you want to regenerate. For example, skin is going to take, let's say,
- one month to heal, but bone will take much longer.
- So we have designed scaffolds according to the tissues that we want to regenerate.
- Sir Robin Grimes: Right, okay. So you're going to be busy looking for scaffolds for a long time!
- That's really very good! Now, I know we've got a little bit of time to have a chat. And this seems
- very unfair to everybody else. I can see that there are some questions starting to come up.
- Before we go to that, I wanted to ask you a little bit about, you've talked to us about your research
- centre, and so I think I understand that, but I'm thinking perhaps about the wider networks that you
- work with, perhaps particularly in Africa. Can you tell us a little bit about those, please?
- Dr Nowsheen Goonoo: Yes. So I form part of the young affiliates of
- two African organisations, namely the African Academy of Sciences and the World Academy of
- Sciences. Now the African Academy of Sciences is a non-political and non-profit organisation,
- and its main aim is to promote or and recognise scientific excellence in Africa.
- So each year it selects through a peer review process, early career researchers, which
- it's going to integrate in its young affiliates programme. Now what happens as a young affiliate,
- is that you are able for a period of five years to receive career support and also mentorship
- from recognised researchers worldwide. You're also able to access different networking opportunities,
- which helps the early career researchers to progress in their career. The World Academy
- of Sciences, just like the African Academy of Sciences, has the same aim. In addition,
- it helps to promote north south and north north collaborations. It also offers several
- fellowships for postdocs and PhD students and also several conference, possibilities to attend
- conferences and also different prizes for PhD students and postdocs. All this is done just
- to recognise African researchers who are working in this, in science in general.
- Sir Robin Grimes: Well I think that's a really useful
- comment actually, because there's an awful lot of people listening to this,
- this evening or this morning, or wherever they are on the planet. What you've done there is given
- them some opportunities to start to develop, how to interact better and more fully with
- other people in African institutions. So I think that's a really important comment that
- you've made there. Now I wanted to go back to some of the science that you're doing, and I'm
- going to start including some sort of questions that we have. So we've got one here about how do
- you extract the polymers from the seaweed? Can you tell us a little bit about that process?
- Dr Nowsheen Goonoo: I'm sorry, can you repeat the question?
- Sir Robin Grimes: Sure. How do you extract the polymers from seaweed?
- Dr Nowsheen Goonoo: Yes. So the extraction process will depend on the polymer that we want to have at
- the end. For example, if you're starting with red seaweeds, you want to have, for example,
- kappa carrageenan. If you start with brown seaweeds, you want to have fucoidan at the end,
- so the extraction process is going to be different, but overall the process that
- we work with is using the alkali process and then precipitation and alcoholic condition.
- So it's a very simple process. The yield also is dependent on the polymer that we are
- extracting. For example, for kappa carrageenan, the yield is quite high, it's up to 70 per cent,
- but for fucoidan we have a lower yield which is less than 20 per cent sometimes.
- Sir Robin Grimes: Do you think that will impact on the industrialisation of this process?
- Dr Nowsheen Goonoo: Yes, certainly. That's why we are we have been concentrating on kappa
- carrageenan up to now. We have seen that fucoidan shows much better properties.
- So what we're trying to do now is to look at other methods of extracting fucoidan from the
- brown seaweeds. We are looking at microwave assisted extraction of fucoidan right now.
- Sir Robin Grimes: Okay, that's quite interesting. It actually follows into a question that,
- [?Jakob 0:32:32:8], has asked. The previous question was by [?Vestan 0:32:36:6] by the way.
- Jakob says here, what are your main goals with the process for the next five years?
- Dr Nowsheen Goonoo: Okay. So in terms of my goals is to optimise the extraction process so that we
- have better yields, especially for fucoidan, and to minimise the use of solvents as much
- as possible, because when we are moving up to a large scale, we want to reduce the cost as well.
- We are looking also at environmental friendly processes, which will be easy to scale up.
- As we have seen through the presentation, we have already performed animal studies. So the next
- stage will be to perform in vivo diabetic wound healing studies, because the studies that have
- shown were not diabetic wound healing studies, they were just normal wound healing studies.
- So this will be the next step. Then after the diabetic wound healing studies, we are hopefully
- looking forward to being able to carry out other clinical trials on human patients in Mauritius
- and then hopefully be able to come up with the first
- Mauritian nanotechnology product in terms of wound care for diabetics in their local continent.
- Sir Robin Grimes: Okay. That really is very, very interesting.
- I'm sorry to the people who are asking questions, I'm not doing this in a particularly good order,
- I'm afraid I apologise. I think actually [?Ilias 0:34:04:02] asked a question here which I think
- follows on very nicely to that. Is when will skin regeneration therapy be available for patients?
- Dr Nowsheen Goonoo: Actually skin regeneration therapy is already available. So we already have
- quite a few commercial products on the market. The problem with these products is that they
- are very expensive, and if we look at the African context, the cost is something which
- not everybody can afford. The second thing is that the logistics, which are involved in storing
- those products and in shipping those products to the African continent, is not something which is
- feasible for Africans. So that's why we are looking into alternatives
- to make cheaper skin regeneration products for the African continent. So the commercially available
- products right now are mainly collagen based. So that's why they are very, very expensive.
- Sir Robin Grimes: Okay. I suspect though that the range of different
- morphologies and things that you have available to you from the natural products may well
- actually make a rather better therapeutic outcome! Of course, that's what you're trying to do, isn't
- it, and also why you've got this prize. Now there is another question, and I apologise, this is from
- Susan [?Grahaf 0:35:27:7], and she said… She's thanked you for the seminar as well, I should say,
- I should say that! When the nanoengineered seaweed is made, and its [?phyllosilicates 0:35:44:9]
- used. I'm not quite sure whether or not there's a typing issue there. So if Susan would like to
- retype that if that isn't quite right, but does that make sense to you?
- Dr Nowsheen Goonoo: No, I'm sorry, I didn't quite get the question.
- Sir Robin Grimes: Oh, it's poly silicate.
- Dr Nowsheen Goonoo: Okay. No, we do not. Yes, I got it now, thank you. So
- in response to Susan's question though, we do not use any silicates in the scaffolds. It's just
- biodegradable polymers for the reason that we want the scaffold to dissolve away
- when the tissue is regenerated. So we only make use of a polyester in general to give mechanical
- strength to the scaffold. We use a polysaccharide to give this bioactive component to the scaffold.
- Sometimes we add in small amounts less than five weight percent, we add natural
- molecules to help with the different phases of the wound healing process. For example,
- we could add curcumin, for example, to help with the inflammation part,
- and we have other molecules that we are looking at to help with each aspect of the wound healing
- phase. The main component of the scaffold remain a biodegradable polyester and the polysaccharide.
- Sir Robin Grimes: Okay. It almost makes me want to ask you a question, when you first started out,
- because there's so much polymer chemistry here that you that you have your fingers on
- all that polymer chemistry. I can see you really understand it, thoroughly.
- Did you start off as a polymer chemist, or did you start off in a chemistry degree?
- Dr Nowsheen Goonoo: Yes, so I started with an undergraduate degree in chemistry,
- and then I specialised and did a postgraduate degree and studies in polymer chemistry.
- Then in my postdoctoral years, I further specialised to learn more about cell biology,
- biomaterial science, engineering, material science, and things like this.
- Sir Robin Grimes: Okay, so you came at it in that direction, thank you. So, Jeffrey Greenspan
- has asked a few questions here, and I'm going to start with this one. Do different seaweeds
- differentially promote different phases of wound healing? So I think what he's getting at here is
- such that a mixture of different seaweed extracts provide optimal wound healing.
- Dr Nowsheen Goonoo: Yes, so actually, yes. We have observed this, but not with kappa
- carrageenan and fucoidan. From the slides that I have shown, we see clearly that, for example,
- in the inflammatory phase, both polysaccharides, they do not behave in the same way. So it is very,
- very possible that for the other phases as well, the two polysaccharides behave very differently.
- We do not observe significant differences for these two polysaccharides that we have looked at.
- These were very preliminary results, we have to look into more in depth in terms of 3D
- cell cultures, especially for the proliferative and remodelling aspects.
- We are sure that this is going to be something really interesting that we need to look at.
- Sir Robin Grimes: Okay, yes. He'd asked a previous question actually, do some seaweeds
- promote one characteristic but not the other? I think you've addressed that in your answer then,
- haven't you? Now Professor [?Thun 0:39:36:1] has then asked another question about going
- back to the issue of extraction of the scaffold materials, and he's asking about the purity
- of the materials. How do you think about the different purities of your scaffold materials?
- Dr Nowsheen Goonoo: So in terms of the polyesters, we buy the polyesters. So it's over 99.9 per
- cent purity. Concerning the extracted polymers, they are also, 98 per cent to 99 per cent pure.
- Sir Robin Grimes: Oh okay. Because these are natural materials, of course,
- you must get quite a lot of variability from the different seaweeds, perhaps even across different
- periods of time. Although I guess in Mauritius you don't have very big
- changes in sea temperatures or do you, across the year?
- Dr Nowsheen Goonoo: No, we don't have big changes in temperature. During the extraction process,
- by controlling time, for example, and temperature and concentration and other things like this,
- we are able to extract a specific polymer with a specific [?molar 0:40:57:4] mass.
- Sir Robin Grimes: Actually, Connie, has asked a question here, which following on from the
- same thing. Would the seaweed type need to be adjusted for people who require or want
- skin regeneration but are using medications such as antibiotics to treat other medical problems.
- Dr Nowsheen Goonoo: In terms of adjustment, I'm not sure what
- the latter means. Actually what I want to add is that if a person is taking antibiotics,
- for example, there is the possibility of including those antibiotics in the scaffold and then having
- it released slowly over time so that the person doesn't need to take the antibiotics orally. If,
- for example, that person is taking antibiotics for an infection occurring at the wound site,
- then it's even better because the release is occurring at the local site of the infection,
- and it's going to be more optimal treatment compared to taking the antibiotics orally.
- Sir Robin Grimes: Yes, I think that's a really, really interesting point here.
- So your materials are going to have an incredible variety of different jobs to do
- for these sorts of wounds. You've talked about diabetic wounds in particular, do you see other
- types of wounds, other types of issues, being able to be addressed using these sorts of materials?
- Dr Nowsheen Goonoo: Yes. So another aspect of my research deals with the fabrication
- of scaffolds for cancer regenerative purposes. So what we mean by cancer regenerative medicine here
- is basically when we consider a solid tumour and that person has the solid tumour removed,
- there is a wound which is created there. Now we are all aware of the fact that the cancer can come
- back again. So we have recurrence and relapse. So what we are trying to do is through the design of
- those scaffolds we want to have the scaffolds to have two main purposes. So the first purpose is to
- act on the cancer cells, so that to prevent the cancer cells from growing back again
- and at the same time promote the healthy cells to grow and proliferate and close the wound.
- So what we need is therefore to have a balance in the scaffold between a promotion of healthy cells
- and killing of cancer cells. So this is something which is very, very tricky. We have been looking
- at this for over four years now, and it is something which is really complicated. Right
- now in terms of solid tumours, we are looking at pancreatic cancer and melanoma, and those we have
- been considering those polysaccharide derived scaffolds for those purposes as well, and this
- aspect is still under investigation. I can say that the results have been very interesting.
- Sir Robin Grimes: Okay, that really is interesting. So there's a difference between
- the way that a cancer cell, and a healthy cell interact with the scaffold? Any idea why?
- Dr Nowsheen Goonoo: So it has to do with the environment that the cells like, for example,
- for melanoma cells, we observed that fucoidan has a higher cytotoxicity towards melanoma cells.
- It is also cytotoxic at high doses to healthy cells. So the trick is to balance to how the
- fucoidan has the right concentration so that it is able to kill the cancer cells but not
- kill the healthy cells, and at the end help to promote the cells, to the healthy cells to grow.
- So it's having the right dose, which is the trick,
- in getting those scaffolds to work for cancer regenerative medicine.
- Sir Robin Grimes: That really is very interesting. You're not going to have a
- shortage of things to do, are you?! You really are going to be a very busy person indeed!
- Rachel McDonald has asked a question, and she said, how did the seaweed scaffolds compared
- to commercially available products, in promoting wound healing in the
- animal studies. Are the seaweed products more effective than collagen products, for example?
- Dr Nowsheen Goonoo: Yes, so this is a very good question and I must say I was expecting this
- question. So in terms of comparison of the performance, I must say that they are both,
- the performance is comparable for both commercial and our fabricated scaffolds. If we look at the
- animal studies, what we note is that the wounds treated with our fabricated scaffolds take longer
- time to heal, compared to the commercial collagen products, for example. This is not a bad thing.
- Why? Because when we look at histology images and we look at the cross-section of the tissues of the
- wound that was closed, what we note is that all the commercial product, the wound closed, but it
- was only superficial. So you have only superficial wound closure, but inside it was hollow. So there
- was still tissue which was not filled inside the wound. In comparison to the wounds which
- were treated using our fabricated scaffold. The tissue started to grow from the inside and then
- completely closed the wound. So there was no hollow space inside the wound. So one of the
- main complications or main issues that we observe with diabetic foot ulcer is that the wounds,
- once they have closed, they reopen with time. This is why it reopens with time, because the
- wound is not completely closed, it's closed only superficially. So it's very important to have the
- tissue grow from within the wound and then close also at the surface. So this is something that
- we are very happy about, that even though our scaffolds take slightly longer time to heal,
- the wound or the new tissue that is formed is much better compared to the new tissue
- that is formed using commercially available products. The second thing is that the wounds,
- when they are treated with a seaweed derived polysaccharide, they do not lead to scarring.
- This is something which nobody would like, that he's having a scar after you have a wound.
- Sir Robin Grimes: Oh, that's interesting. Oh, that is a tremendous advantage, actually.
- Okay, so Jeffrey Greenspan's come back. He's asked whether the scaffolds promote cytokine production.
- Dr Nowsheen Goonoo: Yes, they promote cytokine production, especially in the inflammatory phase.
- For example, fucoidan promotes both pro-inflammatory and anti-inflammatory
- cytokines and the same for kappa carrageenan polysaccharides, and depending on
- the concentration that the polysaccharides are being used, the concentration of cytokines that
- is going to be produced is also going to vary. If we compare, for example,
- both polysaccharides at the same concentration, we note that the fucoidan containing polysaccharide
- will cause the formation of anti-inflammatory cytokines compared to kappa carrageenan. So
- it promotes macrophages via the secretion of cytokines towards the pro-healing phenotype.
- Sir Robin Grimes: Okay, so that really is part of the advantages,
- compared to commercially available products at the moment in fact, okay, that is interesting.
- You talked a little bit about piezoelectric polymers and how
- a mechanism by which that might play a role here. I have to say, I'm quite interested in that,
- in piezoelectric materials in general terms. If you apply an external electric field, then,
- could you change or use that piezoelectric behaviour as part of the therapeutic process?
- Is there something that you could do using the piezoelectric nature of these materials?
- Dr Nowsheen Goonoo: So the goal, or the aim of using piezoelectric polymer is
- so as to not be dependent on an external electric supply or power supply. So we don't want to have,
- to add an electric current or a voltage to provide this piezoelectric property.
- So for these piezoelectric polymers, for example, if you apply this to an animal for example,
- through the motion of the animal, this is going to cause micro deformations on the scaffold,
- and this in itself is going to bring about the piezoelectricity. This is going in turn to trigger
- a cellular response and cause cell proliferation and wound closure, as we have seen over time.
- Sir Robin Grimes: Okay, but there is a possibility that if you if you did apply
- an external electric field, you could get an additional effect, in fact, on these materials.
- Dr Nowsheen Goonoo: Yes, yes. It's possible that we can have an additional effect, but this is not
- something that we are looking at because it's going to further complicate the process, and we
- want to have something which is a very simple and very easy to apply in clinical settings.
- Sir Robin Grimes: Yes, quite right, keep it simple! It's complicated enough as
- it is! John Percival's asked, how relevant is this technique to burn treatment?
- Dr Nowsheen Goonoo: It's as effective as for diabetic foot ulcers. So all the scaffolds that
- we have designed for skin regeneration can be applied for burn wounds as well,
- but we have not tested them on in vivo models yet, we have tested them only on ex vivo
- models, and so far we have seen very good results. So this is another direction in
- which we are planning to go and look at in terms of burn wounds. We are very
- happy that the results have been very positive for both burn wounds and diabetic foot ulcers as well.
- Sir Robin Grimes:
- You're doing a tremendous amount of work. Can you remind us, how big is your group now?
- Dr Nowsheen Goonoo: So the research centre that I work at, currently we are
- a total of 15 people. So we have two permanent staff, and we have ten postgraduate students,
- and three research assistants. It's not a very big group, but we're doing the best we can.
- Sir Robin Grimes: Well, you are doing very well! You just won a prize. I think that that says it
- all, does it not?! Yes, I think you must all be working every hour that it's possible to have
- created so many absolutely fascinating results. So we are actually getting towards the end of our
- time here today, so I'd like to encourage if there's anyone who wants to ask any other
- questions to quickly type away. We don't have very we don't have very long left to do that.
- Nowsheen, is there anything you wanted to say to us in these closing few minutes?
- Dr Nowsheen Goonoo: Yes. I would like to convey a message, especially to
- early career researchers and postgraduate students. I would like to say to them that
- if you want to go ahead in your career, it's very important to plan ahead, always have a
- personal development plan, and remember to update your personal development plan as you go along
- and always give yourself deadlines. That is, if you say that I want to achieve this or I want to
- improve for example my communication skills, set up a goal, have a vision first, set goals, make
- plans. Once you have made plans, assess yourself whether those plans have been successful or not
- and take the required action. So the most important thing is to always have plans ahead.
- This is also applicable to writing grants, to applying for grants, for example, applying for
- prizes, for fellowships, always have in mind what you want to have, what you want to be, where you
- want to see yourself in five years' time, and constantly review your personal development plan.
- Sir Robin Grimes: I must admit, I really admire your determination. I really, I really do. That's
- extremely good advice, it really is. I think also you're doing something that you really
- care about, and you're doing something that you are obviously absolutely fascinated with. I must
- say, I think that is also incredibly important for success because it allows you to drive to action,
- doesn't it? If you're doing something that you really, really believe in.
- Dr Nowsheen Goonoo: Absolutely. So I think that if you like what you're doing, then work is not
- really work. So it's something that you live for, actually. So it becomes your passion,
- and then you are determined to make it work, to try to find solutions. I think it's the case for
- all scientists across the world. So once you set a target, you will do your best to achieve it.
- Sir Robin Grimes: Absolutely. Well, there is no doubt whatsoever that you are achieving it.
- As we come to the end of our of our time,
- I wanted to thank you very, very much for your lecture, which which was just
- a really good example of a great lecture. I really enjoyed it very much. You fielded lots and lots of
- diverse questions. I loved your comment that, ah, that's a question I was expecting! That
- I enjoyed that very much. Thank you for really educating me as well, as I said, this is not
- an area that I was terribly familiar with and I've learned an awful lot. I think
- that's how you know it's been a great lecture, so thank you very much indeed.
- As we finish today, I also wanted to let everybody know that the next public lecture
- is the Rosalind Franklin lecture. It's going to be given by Suzanne Imber, who's a planetary
- scientist from the University of Leicester. That's going to be on the 9th of February. So
- having said that, again, Dr Goonoo, I just want to thank you for being our rising star and the first
- recipient of this prize. You've set the bar very high. So thank you very much indeed, thank you.
- Dr Nowsheen Goonoo: Thank you.
Join Dr Nowsheen Goonoo to discover how seaweed can be turned into affordable dressings for fast and scarless wound healing, especially for diabetic foot ulcers.
Type 2 diabetes is a worldwide issue leading to major complications such as diabetic foot ulcers (DFUs). The lifetime risk of developing diabetic foot ulcer (DFU) is 15% and patients have a 75% mortality rate if DFU is combined with nephropathy. In Africa, approximately 2.4 million diabetics suffer from DFUs. The main common forms of DFU treatment is surgical debridement, dressings and antibiotics therapy. DFUs add significantly to the economic burden of a country due to ulcer management, slow healing which leads to prolonged admissions and surgical interventions. As a result, there is an urgent need to reduce the healing time of DFUs, thereby reducing the number of hospital admissions and amputation rates.
Difficulties in repairing wounds related to DFUs are mainly due to wound infection, lack of extracellular matrix (ECM), and insufficient blood supply in the affected area. Current commercial products for the treatment of DFUs are very expensive and find limited applications on the African continent. In her lecture, Dr Goonoo will share her experiences on the transformation of seaweeds into affordable nanofiber-based wound dressings to promote scarless and accelerated wound healing.
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