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Cartilage tissue engineering: current scenario and challenges

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Review Article Adv. Mat. Lett. 2011, 2(2), 90-99 ADVANCED MATERIALS Letters<br />

more proteins that can stick to cells to enhance cellscaffold<br />

interaction.<br />

8. Obstacles <strong>and</strong> future perspectives in cartilage<br />

regeneration<br />

A number of obstacles in the way of optimal cartilage<br />

repair remain to be surmounted. These hurdles are<br />

associated with the three cornerstones of cartilage <strong>tissue</strong><br />

<strong>engineering</strong>: cells, scaffold <strong>and</strong> growth factors. The major<br />

challenging issues associated with cartilage <strong>tissue</strong><br />

<strong>engineering</strong> are summarised in Fig. 11. The key cell related<br />

issue is how to enhance chondrogenesis, <strong>and</strong> how<br />

biophysical, chemical <strong>and</strong> mechanical stimuli can be<br />

introduced within the cells to promote chondrogenesis.<br />

Major scaffold related issue includes the fabrication of<br />

scaffold in such a way that can exactly mimic the natural<br />

environment of the <strong>tissue</strong>. As far as growth factors are<br />

concerned, very little is known about the sequences <strong>and</strong><br />

concentrations of growth factors for which cartilage<br />

regeneration is optimized.<br />

Although cartilage regeneration is complex <strong>and</strong> affected<br />

by multiple growth factors which are released in a wellorchestrated<br />

manner, but most of the studies involved use<br />

of single growth factor. A little number of systems have<br />

been developed been developed that allow the biphasic<br />

release of dual growth factors. An example is the<br />

encapsulation of IGF-1 in gelatin spheres that are then<br />

suspended in oligo[poly(ethylene glycol) fumarate]<br />

scaffolds containing TGF-1.This system provides a fast<br />

release of TGF-1 <strong>and</strong> a more sustained delivery of IGF-1<br />

to promote cartilage repair [56]. Dual growth factor<br />

releasing alginate based nanoparticle/hydrogel system was<br />

recently used to deliver BMP-7 <strong>and</strong> TGFβ-2 to promote<br />

Fig. 11. Major challenging issues in cartilage <strong>tissue</strong> <strong>engineering</strong>.<br />

chondrogenesis in MSCs [57]. Thus, there is a need to<br />

focus on the study of releasing multiple growth factors at a<br />

time, to favour the production of more natural cartilage<br />

<strong>tissue</strong>.<br />

Furthermore, it should be kept in mind that most of the<br />

studies in cartilage <strong>tissue</strong> <strong>engineering</strong> were performed using<br />

mostly young adult <strong>and</strong> even fetal animal cells, <strong>and</strong> not with<br />

cells from elderly osteoarthritis patients. Therefore,<br />

extensive research on using the cells from elderly<br />

osteoarthritis patients will be needed to extend the results<br />

for treating human cartilage defects.<br />

The final <strong>and</strong> probably most difficult problem is how to<br />

translate the results of in vitro <strong>and</strong> animal studies into<br />

clinical application <strong>and</strong> thereby introduction to market. To<br />

date, a large number of new cartilage products <strong>and</strong> growth<br />

factor carrier materials have been developed, but only few<br />

of them are approved for use in patients. Some of the major<br />

reasons for the small numbers of approved products<br />

include, hurdles posed by the cost of development, cost of<br />

goods, manufacturing scale-up, sterility <strong>and</strong> patent issues.<br />

In addition, there are many regulatory hurdles, including<br />

quality control <strong>and</strong> quality assurance for consistent<br />

manufacturing, comparability studies required for<br />

component <strong>and</strong> process changes, establishment of shipping<br />

<strong>and</strong> storage conditions, <strong>and</strong> appropriate shelf life [58].<br />

Already existing as well as new cartilage <strong>engineering</strong><br />

products should be approved by the government<br />

organizations so that they can be easily available for<br />

clinical applications. Most importantly, major efforts are<br />

needed to move the obtained results in laboratory towards<br />

the application for treating human cartilage defects [58].<br />

This can be solved, to certain extent, by making the cost<br />

effective <strong>tissue</strong> engineered products. Moreover, the <strong>tissue</strong><br />

engineered solution for cartilage repair must involve<br />

minimal donor site morbidity <strong>and</strong> should be free of any<br />

Adv. Mat. Lett. 2011, 2(2), 90-99 Copyright © 2011 VBRI press. 97

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