Tunable Hydrogel-Polyester Combination Scaffolds for Tissue Engineering Purposes

Jasper Van Hoorick Peter Dubruel Sandra Van Vlierberghe
Gummibeertjes tegen rugpijn.  InleidingChronische rugklachten, wat nu? Geraak je ervan verlost, of blijven ze de rest van je leven hangen? Een struikelblok dat de geneeskunde nog niet volledig heeft weten weg te werken. Maar mocht je het kapotte onderdeel nu eens simpelweg kunnen vervangen door een gloednieuw wisselstuk, net als bij een auto?

Tunable Hydrogel-Polyester Combination Scaffolds for Tissue Engineering Purposes

Gummibeertjes tegen rugpijn. 

 

Inleiding

Chronische rugklachten, wat nu? Geraak je ervan verlost, of blijven ze de rest van je leven hangen? Een struikelblok dat de geneeskunde nog niet volledig heeft weten weg te werken. Maar mocht je het kapotte onderdeel nu eens simpelweg kunnen vervangen door een gloednieuw wisselstuk, net als bij een auto?  Kan een combinatie van 3D printen en gelatine, de grondstof van gummibeertjes, de oplossing bieden om wisselstukken te generen uit lichaamseigen cellen?

 

Rugklachten

Rugpijn is in België, en bij uitbreiding in de Westerse wereld, één van de belangrijkste chronische lichamelijke aandoeningen. Ondanks het feit dat de specifieke oorzaken vaak onduidelijk zijn, heeft men reeds kunnen aantonen dat het dikwijls een gevolg is van degenererende tussenwervelschijven. Dit zijn de “scharnieren” tussen de verschillende ruggenwervels, die beweging van de ruggengraat mogelijk maken en tegelijkertijd de schokken in onze rug opvangen. Ze bestaan uit drie kenmerkende onderdelen: een gelatineuze kern  (nucleus pulposus) omgeven door een cilinder bestaande uit vezelig kraakbeen (annulus fibrosus) die samen tussen twee kraakbeen eindplaten liggen. De kern fungeert als de schokdemper, terwijl de cilinder eerder de zijwaartse krachten op de ruggengraat opvangt. De eindplaten vormen de verbinding met de ruggenwervels.Naarmate je ouder wordt, kunnen verschillende zaken optreden die tot specifieke rugklachten kunnen leiden. Enerzijds kan de hoeveelheid water in de kern gaan afnemen waardoor de tussenwervelschijf zal verdunnen. Hierdoor zal het absorptievermogen van de tussenwervelschijf sterk afnemen en  de bewegingsvrijheid van de ruggenwervels verminderen. Een ander veel voorkomend probleem is de vorming van scheurtjes in de cilinder. Hierdoor kan de zachtere kern gedeeltelijk naar buiten worden geduwd, met een uitstulping of hernia tot gevolg. Wanneer deze bult druk op de rugzenuw uitoefent kan dit leiden tot chronische rugpijn. De meest courante behandeling bestaat momenteel uit injecties in de kern om deze te doen krimpen waardoor de bult terug naar binnen gezogen wordt en de rugpijn vervolgens afneemt of zelfs verdwijnt. Ondanks succes in pijnbestrijding vormen deze behandelingen echter geen duurzame oplossing voor het probleem. Na verloop van tijd dient de beschadigde tussenwervelschijf immers dikwijls geblokkeerd te worden met vijzen, waardoor de beweeglijkheid van de ruggengraat nog verder zal afnemen en de overige tussenwervelschijven zwaarder belast worden.

 

Duurzame oplossing

Om het probleem op lange termijn te behandelen zou men de beschadigde tussenwervelschijven moeten vervangen. Dit kan op twee manieren: enerzijds kan een volledig synthetische prothese ingebouwd worden die de functies van de tussenwervelschijf overneemt. Anderzijds kan toevlucht gezocht worden in regeneratieve geneeskunde waarbij nieuwe tussenwervelschijven gekweekt worden uit lichaamseigen cellen.  Het gebruik van prothesen lijkt de eenvoudigste methode, maar heeft enkele problemen waaronder povere aanhechting aan de ruggenwervels, verre van optimale mechanische eigenschappen en de vorming van vijlsel bij veelvuldige beweging. De duurzaamste oplossing lijkt dus te liggen in de regeneratieve geneeskunde, waarbij de aandacht in het onderzoek vooral ging naar de ontwikkeling van geschikte weefseldragers voor het kweken van nieuwe tussenwervelschijven met behulp van stamcellen.

 

Onderdeel kapot, wisselstuk klaar?

Opdat een succesvol wisselstuk terug kan ´groeien´ is het belangrijk dat de cellen voldoende plaats krijgen om te kweken, er voldoende transport van voedingstoffen en afvalstoffen is en dat het wisselstuk uiteindelijk de juiste vorm aanneemt. Om hieraan tegemoet te komen, wordt gebruik gemaakt van biodegradeerbare poreuze draagstructuren. Deze dragers zullen na implantatie geleidelijk aan afgebroken worden, terwijl de afgezette cellen zullen groeien en delen. Hierdoor zullen op termijn enkel lichaamseigen cellen achterblijven zonder een spoor van het implantaat. Het is belangrijk dat de drager tijdens dit proces voldoende mechanische eigenschappen van de te vervangen tussenwervelschijf kan nabootsen totdat het gevormde weefsel sterk genoeg is om deze taak over te nemen. Naast biodegradeerbaar moeten de ´mallen´ ook biocompatibel zijn om interactie met de cellen mogelijk te maken en geen aanleiding te geven tot ongunstige reacties van het immuunsysteem. Verder dienen deze structuren poreus te zijn om voldoende transport van voedings- en afvalstoffen van en naar het groeiende weefsel te verzekeren. 

 

Toegepaste bouwstenen

Om aan bovenvermelde zaken te voldoen werd in de studie gebruik gemaakt van twee materialen in combinatie met 3D-printen om de porositeit en morfologie van de implantaten te verzekeren. Enerzijds werd gelatine aangewend, vanwege zijn gunstige bio-compatibiliteit en mechanische gelijkheid aan de nucleus pulposus.  Gelatine is een hydrogel materiaal, een moleculair netwerk dat grote hoeveelheden water kan opnemen (zoals bijvoorbeeld contactlenzen). Het vormt echter een fysisch netwerk dat zal oplossen bij lichaamstemperatuur, waardoor het noodzakelijk is om gelatine chemisch te modificeren en op die manier een onoplosbaar chemisch netwerk te verkrijgen alvorens dit te gebruiken in het lichaam. Deze modificatie is gebeurd door het inbouwen van actieve groepen (methacrylaten en methacrylamides) op de verschillende gelatineketens, die onder invloed van licht met elkaar kunnen reageren en zo een chemisch netwerk zullen vormen. De studie heeft ook aangetoond dat de mechanische eigenschappen van het ontwikkelde gelatinederivaat gecontroleerd kunnen worden door het aantal ingebouwde groepen te variëren, waardoor de mechanische eigenschappen van het te vervangen weefsel zeer dicht benaderd kunnen worden. Naast gelatine werd ook gebruik gemaakt van een biodegradeerbaar polyester (polymelkzuur), verwerkt via 3D printen, om de vorm en mechanische stijfheid (noodzakelijk voor de annulus fibrosus) aan de drager toe te kennen. Het 3D printen biedt een zeer groot potentieel in de regeneratieve geneeskunde, aangezien dit toelaat om nagenoeg perfecte kopieën van beschadigd weefsel te produceren via modellen verkregen via bijvoorbeeld MRI scans.

 

Eerste resultaten

De eerste celtesten op een combinatie van gelatine met polyesters voor weefselregeneratie waren reeds veelbelovend. Zo bleken deze materialen voldoende bio-interactief om het kweken van cellen toe te laten. Bovendien heeft het onderzoek aangetoond dat het mogelijk is om het gelatinenetwerk pas te vormen nadat de cellen reeds in de oplossing gebracht werden, waardoor deze beter verdeeld kunnen worden binnenin de drager. Ook werd het potentieel aangetoond van op maat gemaakte 3D structuren die kunnen leiden tot patiënt-specifieke, lichaamseigen wisselstukken voor verschillende aandoeningen. Op dit moment is de finale toepassing echter nog toekomstmuziek en dient er nog heel wat onderzoek verricht te worden alvorens het kan aangewend worden in de geneeskunde. Een kleine stap dichter bij de (her)maakbare mens... 

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Universiteit of Hogeschool
Master of Science: Chemistry
Publicatiejaar
2014
Kernwoorden
@JasVanHoorick
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