Type I diabetes mellitus (T1DM) is an autoimmune disease caused by auto-reactive T-cell-mediated destruction of insulin-producing β-cells. Effective encapsulation strategies can protect the transplanted islets from direct attack by host immune cells while maintaining insulin secretion. To achieve this goal, I have developed a hydrogel conformal coating using a visible light-mediated interfacial thiol-ene photopolymerization. Unlike conventional chain-growth visible light polymerizations, no additional cytotoxic co-initiator or co-monomer was required in thiol-ene gelation scheme for rapid gelation. More importantly, islets coated with thiol-ene gel maintained their viability and function in vitro. In addition to microencapsulate β-cells, the second objective of my dissertation focuses on developing a macroencapsulation technique using thiol-ene hydrogel with bioactivity and anti-inflammatory property. While islet transplantation holds potential in permanently reversing T1DM, this procedure initiates a cascade of inflammatory processes. To address this issue, we have developed thiol-ene hydrogel crosslinked by thiolated β-cyclodextrin (βCD). The conjugation of amphiphilic βCD affords enhanced loading and prolonged release of curcumin, an anti-inflammatory drug candidate but with poor water solubility. In addition, bioactive peptide such laminin-derived peptide flanked with two cysteine residues could be readily incorporated through orthogonal crosslinking, thus mimicking extracellular microenvironment in the pancreatic islets. Finally, in order to provide coated β-cells with an ideal biomechanical microenvironment, it is essential to identify a suitable gel stiffness to support the viability and functions of β-cells. To this end, a thiol-allylether hydrogel with on-demand tunable matrix stiffness was developed. Specifically, host molecule βCD was immobilized in the hydrogel network to provide binding sites for soluble guest molecule poly(ethylene glycol)-adamantane. Gel stiffness was tuned through introducing reversible host-guest interactions. After in situ stiffening of the cell-laden hydrogel, the encapsulated β-cells showed increased in insulin mRNA expression, suggesting the profound impact of matrix stiffness on pancreatic β-cell fate.
","abstract_html":"<p>Type I diabetes mellitus (T1DM) is an autoimmune disease caused by auto-reactive T-cell-mediated destruction of insulin-producing β-cells. Effective encapsulation strategies can protect the transplanted islets from direct attack by host immune cells while maintaining insulin secretion. To achieve this goal, I have developed a hydrogel conformal coating using a visible light-mediated interfacial thiol-ene photopolymerization. Unlike conventional chain-growth visible light polymerizations, no additional cytotoxic co-initiator or co-monomer was required in thiol-ene gelation scheme for rapid gelation. More importantly, islets coated with thiol-ene gel maintained their viability and function <em>in vitro</em>. In addition to microencapsulate β-cells, the second objective of my dissertation focuses on developing a macroencapsulation technique using thiol-ene hydrogel with bioactivity and anti-inflammatory property. While islet transplantation holds potential in permanently reversing T1DM, this procedure initiates a cascade of inflammatory processes. To address this issue, we have developed thiol-ene hydrogel crosslinked by thiolated β-cyclodextrin (βCD). The conjugation of amphiphilic βCD affords enhanced loading and prolonged release of curcumin, an anti-inflammatory drug candidate but with poor water solubility. In addition, bioactive peptide such laminin-derived peptide flanked with two cysteine residues could be readily incorporated through orthogonal crosslinking, thus mimicking extracellular microenvironment in the pancreatic islets. Finally, in order to provide coated β-cells with an ideal biomechanical microenvironment, it is essential to identify a suitable gel stiffness to support the viability and functions of β-cells. To this end, a thiol-allylether hydrogel with on-demand tunable matrix stiffness was developed. Specifically, host molecule βCD was immobilized in the hydrogel network to provide binding sites for soluble guest molecule poly(ethylene glycol)-adamantane. Gel stiffness was tuned through introducing reversible host-guest interactions. After <em>in situ</em> stiffening of the cell-laden hydrogel, the encapsulated β-cells showed increased in insulin mRNA expression, suggesting the profound impact of matrix stiffness on pancreatic β-cell fate.</p>","abstract_has_math":false,"creators":["Shih, Han"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Engineering","degree_department":null,"school":null,"contributors":["Chien-Chi Lin","Raghu Mirmira","Alyssa Panitch","Dong Xie"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-08-01T07:00:00Z","date_published":"2016-08-01T07:00:00Z","updated_at":"2026-07-24T03:54:02Z","subjects":["Applied sciences","Hydrogel","Islets","Macroencapsulation","Microencapsulation","Photopolymerization","Thiol-ene","Biomedical Engineering and Bioengineering"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://docs.lib.purdue.edu/open_access_dissertations/846","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chien-Chi Lin","Raghu Mirmira","Alyssa Panitch","Dong Xie"]},{"key":"dc:creator","label":"Author","values":["Shih, Han"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Applied sciences","Hydrogel","Islets","Macroencapsulation","Microencapsulation","Photopolymerization","Thiol-ene","Biomedical Engineering and Bioengineering"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://docs.lib.purdue.edu/open_access_dissertations/846"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Type I diabetes mellitus (T1DM) is an autoimmune disease caused by auto-reactive T-cell-mediated destruction of insulin-producing β-cells. Effective encapsulation strategies can protect the transplanted islets from direct attack by host immune cells while maintaining insulin secretion. To achieve this goal, I have developed a hydrogel conformal coating using a visible light-mediated interfacial thiol-ene photopolymerization. Unlike conventional chain-growth visible light polymerizations, no additional cytotoxic co-initiator or co-monomer was required in thiol-ene gelation scheme for rapid gelation. More importantly, islets coated with thiol-ene gel maintained their viability and function in vitro. In addition to microencapsulate β-cells, the second objective of my dissertation focuses on developing a macroencapsulation technique using thiol-ene hydrogel with bioactivity and anti-inflammatory property. While islet transplantation holds potential in permanently reversing T1DM, this procedure initiates a cascade of inflammatory processes. To address this issue, we have developed thiol-ene hydrogel crosslinked by thiolated β-cyclodextrin (βCD). The conjugation of amphiphilic βCD affords enhanced loading and prolonged release of curcumin, an anti-inflammatory drug candidate but with poor water solubility. In addition, bioactive peptide such laminin-derived peptide flanked with two cysteine residues could be readily incorporated through orthogonal crosslinking, thus mimicking extracellular microenvironment in the pancreatic islets. Finally, in order to provide coated β-cells with an ideal biomechanical microenvironment, it is essential to identify a suitable gel stiffness to support the viability and functions of β-cells. To this end, a thiol-allylether hydrogel with on-demand tunable matrix stiffness was developed. Specifically, host molecule βCD was immobilized in the hydrogel network to provide binding sites for soluble guest molecule poly(ethylene glycol)-adamantane. Gel stiffness was tuned through introducing reversible host-guest interactions. After in situ stiffening of the cell-laden hydrogel, the encapsulated β-cells showed increased in insulin mRNA expression, suggesting the profound impact of matrix stiffness on pancreatic β-cell fate.
"]},{"key":"dc:title","label":"Title","values":["Development of orthogonally crosslinked thiol-ene hydrogels for encapsulation of pancreatic beta-cells"]}]}],"canonical_facts":{"dc:contributor":["Chien-Chi Lin","Raghu Mirmira","Alyssa Panitch","Dong Xie"],"dc:creator":["Shih, Han"],"dc:description.abstract":["Type I diabetes mellitus (T1DM) is an autoimmune disease caused by auto-reactive T-cell-mediated destruction of insulin-producing β-cells. Effective encapsulation strategies can protect the transplanted islets from direct attack by host immune cells while maintaining insulin secretion. To achieve this goal, I have developed a hydrogel conformal coating using a visible light-mediated interfacial thiol-ene photopolymerization. Unlike conventional chain-growth visible light polymerizations, no additional cytotoxic co-initiator or co-monomer was required in thiol-ene gelation scheme for rapid gelation. More importantly, islets coated with thiol-ene gel maintained their viability and function in vitro. In addition to microencapsulate β-cells, the second objective of my dissertation focuses on developing a macroencapsulation technique using thiol-ene hydrogel with bioactivity and anti-inflammatory property. While islet transplantation holds potential in permanently reversing T1DM, this procedure initiates a cascade of inflammatory processes. To address this issue, we have developed thiol-ene hydrogel crosslinked by thiolated β-cyclodextrin (βCD). The conjugation of amphiphilic βCD affords enhanced loading and prolonged release of curcumin, an anti-inflammatory drug candidate but with poor water solubility. In addition, bioactive peptide such laminin-derived peptide flanked with two cysteine residues could be readily incorporated through orthogonal crosslinking, thus mimicking extracellular microenvironment in the pancreatic islets. Finally, in order to provide coated β-cells with an ideal biomechanical microenvironment, it is essential to identify a suitable gel stiffness to support the viability and functions of β-cells. To this end, a thiol-allylether hydrogel with on-demand tunable matrix stiffness was developed. Specifically, host molecule βCD was immobilized in the hydrogel network to provide binding sites for soluble guest molecule poly(ethylene glycol)-adamantane. Gel stiffness was tuned through introducing reversible host-guest interactions. After in situ stiffening of the cell-laden hydrogel, the encapsulated β-cells showed increased in insulin mRNA expression, suggesting the profound impact of matrix stiffness on pancreatic β-cell fate.
"],"dc:identifier":["https://docs.lib.purdue.edu/open_access_dissertations/846"],"dc:subject":["Applied sciences","Hydrogel","Islets","Macroencapsulation","Microencapsulation","Photopolymerization","Thiol-ene","Biomedical Engineering and Bioengineering"],"dc:title":["Development of orthogonally crosslinked thiol-ene hydrogels for encapsulation of pancreatic beta-cells"],"thesis:degree_discipline":["Biomedical Engineering"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:54:02Z"}