Tailoring supramolecular glycosaminoglycan-based hydrogels to guide cell behavior

Project Description: 

Biomaterials for tissue engineering are designed to promote the formation of functional tissues to replace lost or damaged tissues. Despite significant progress in biomaterials design and synthesis, the resulting engineered  tissues  are  functionally  inferior  to  native  tissues.  This  is  largely  because  of  the  inability  to recapitulate  the  dynamic  and  complex  nature  of  the  extracellular matrix  (ECM)  that  surrounds  cells  in tissues. ECM composition varies depending on the specific tissue and is remodeled and reorganized over time  during  homeostasis  and  in  response  to  major  events,  such  as  injury  or  disease.  Specifically, glycosaminoglycans   (GAGs)  are  important  ECM  biomolecules  that  exist  in  varying  compositions  indifferent  tissues.  The GAG  chemistry  and  concentration  is modified  at  different  times  by  cellGmediated processes to regulate cellGcell and cellGECM interactions. The overall goal of the proposed BDSI project is to develop supramolecular GAGGbased hydrogels with tunable properties to influence cell behavior. The fundamental hypothesis of the proposed research is that modifying hydrogel composition will significantly affect both materials properties and cell behavior. 


The  proposed  research  plan  for  the  BDSI  summer  program  focuses  on  developing  strategies  to  tune GAGGbased  hydrogel  properties  and  investigate  human  mesenchymal  stem  cells   (hMSCs)  response.  This  project  is  an  expansion  of  previous  results  and  ongoing  work  where  we  have  successfully synthesized GAGGpeptide molecules  that  selfGassemble  into  hydrogels.  The  plan  includes  synthesis  of selfGassembling  GAGGpeptide  molecules,  materials  characterization  of  GAGGpeptide  hydrogels,  and  in vitro experiments with hMSCs encapsulated within the hydrogels. The data resulting from this work will beused to inform future hydrogel formulations and provide key preliminary results necessary for competitive external funding opportunities. 


This  interdisciplinary  project  involves  a  combination  of  chemistry,  materials  science  and  engineering, bioengineering, and cell biology. Two GAG molecules, hyaluronic acid (HA) and chondroitin sulfate  (CS), will be modified with wellGestablished βGsheetGforming peptides to create GAGGpeptide hybrid molecules that crossGlink into a supramolecular hydrogel. The degree of peptide conjugation will be varied to create hydrogels  with  a  range  of mechanical  properties.  Notably,  the  modular  design  of  these  GAGGpeptide molecules  allows  coGassembly  at  desired  ratios  to  create multiGGAG  hydrogels.  This  also  allows  us  to form hydrogels with matching mechanical properties but different biochemical compositions to decouple how  mechanical  and  biochemical  cues  influence  hMSC  behaviour.  In  addition,  the  nonGcovalent crosslinking  introduces  selfGhealing  properties  that  enable  the  recovery  of mechanical  porperties  after large strains for injectable, minimally invasive delivery important for clinical translation. 


Materials  characterization  techniques  will  be  used  to  verify  GAGGpeptide  synthesis  steps  and  assess hydrogel formation, mechanical properties, βGsheet formation, and selfGhealing capacity. A subset of the hydrogel  groups  for  in# vitro  studies  will  be  selected  based  on  matching  mechanical  properties  or biochemical compositions. Human MSCs will be encapsulated within the hydrogels, and a wide range of biological techniques will be used to observe cell behavior in response to the different properties. For the 2017 BDSI Summer Program, we have identified the following key aims: 


Aim)1: Synthesize and characterize singleGGAG hydrogels

Aim)2: Synthesize and characterize multiGGAG hydrogels

 Aim)3: Investigate the effect of hydrogel properties hMSC behavior


During  the  course  of  this  summer  project,  BDSI  students  will  gain  a  wide  range  of  different interdisciplinary  skills  including:  synthesizing  and  characterizing  hydrogelsU  culturing,  monitoring,  and analyzing cellsU designing experimentsU adapting and optimizing protocolsU and improving written and oral communication. Students will also learn how to search and critically review scientific literature related to this project and biomaterials as a whole. 


Project Year: 


Team Leaders: 

Lesley Chow, Ph.D. - Materials Science & Engineering
Sabrina Jedlicka, Ph.D. - Materials Science & Engineering

Graduate Students: 

Swetha Chandrasekar
Hafiz (Dammy) Busari

Undergraduate Students: 

Matthew Green
Ashlinn Sweeney
Xinmeng Qiao
Claire Ternes