{"id":{"repo_id":"rice","oai_identifier":"oai:repository.rice.edu:1911/70319"},"canonical_url":"https://search.dev.ndltd.org/etd/rice/oai:repository.rice.edu:1911/70319","repository":{"repo_id":"rice","name":"Rice University","base_url":"https://repository.rice.edu/server/oai/request"},"display":{"title":"Modulation of Chondrogenic and Osteogenic Differentiation of Mesenchymal Stem Cells through Signals in the Extracellular Microenvironment","abstract":"Damage to synovial joints results in osteochondral defects that only heal with inferior fibrous repair tissue. Since mesenchymal stem cells (MSCs) play a vital role in the natural development, maintenance, and repair of cartilage and bone, tissue engineering strategies to enhance functional regeneration by modulating MSC differentiation are a promising alternative to the limitations and potential complications associated with current conventional therapies. In this work, signals present in the native microenvironment were utilized in fabricating polymer/extracellular matrix composite scaffolds to guide chondrogenic and osteogenic differentiation. In an osteochondral defect environment, interactions exist between bone marrow cell populations. Although MSCs have been extensively utilized for their ability to support hematopoietic stem and progenitor cells (HSPCs), the role of HSPCs in regulating the osteogenic differentiation of MSCs in the bone marrow niche is not well understood, and thus was explored via direct contact co-culture. HSPCs in a low dose with sustained osteogenic induction by dexamethasone accelerated osteogenesis and enhanced mineral deposition, whereas the lack of induction signals affected the spatial distribution of cell populations and minerals. Thus, HSPCs presumably play an active role in modulating the development and maintenance of the osteogenic niche. Since physical signals affect cellular activity, flow perfusion culture was employed to deposit mineralized extracellular matrix (ECM) with different maturity and composition on electrospun poly([varepsilon]-caprolactone) (PCL) microfibers in fabricating mineralized PCL/ECM composite scaffolds. The presence of mineralized matrix induced the osteogenic differentiation of MSCs even in the absence of dexamethasone, and a more mature matrix with higher quantities of collagen and minerals improved osteogenesis by accelerating alkaline phosphatase expression and matrix mineralization. To determine whether PCL/ECM scaffolds can be applied to support the chondrogenic differentiation of MSCs, cartilaginous PCL/ECM composite scaffolds were fabricated. The presence of cartilaginous matrix reduced fibroblastic phenotype and in combination with transforming growth factor-β1 (TGF-β1), further promoted chondrogenesis as evident in elevated levels of glycosaminoglycan synthetic activity. While further investigation is necessary to optimize and test these scaffolds to induce the regeneration of cartilage and bone, this work demonstrates the importance of harnessing signals present in the native microenvironment to modulate chondrogenic and osteogenic differentiation.","abstract_html":"Damage to synovial joints results in osteochondral defects that only heal with inferior fibrous repair tissue. Since mesenchymal stem cells (MSCs) play a vital role in the natural development, maintenance, and repair of cartilage and bone, tissue engineering strategies to enhance functional regeneration by modulating MSC differentiation are a promising alternative to the limitations and potential complications associated with current conventional therapies. In this work, signals present in the native microenvironment were utilized in fabricating polymer/extracellular matrix composite scaffolds to guide chondrogenic and osteogenic differentiation. In an osteochondral defect environment, interactions exist between bone marrow cell populations. Although MSCs have been extensively utilized for their ability to support hematopoietic stem and progenitor cells (HSPCs), the role of HSPCs in regulating the osteogenic differentiation of MSCs in the bone marrow niche is not well understood, and thus was explored via direct contact co-culture. HSPCs in a low dose with sustained osteogenic induction by dexamethasone accelerated osteogenesis and enhanced mineral deposition, whereas the lack of induction signals affected the spatial distribution of cell populations and minerals. Thus, HSPCs presumably play an active role in modulating the development and maintenance of the osteogenic niche. Since physical signals affect cellular activity, flow perfusion culture was employed to deposit mineralized extracellular matrix (ECM) with different maturity and composition on electrospun poly([varepsilon]-caprolactone) (PCL) microfibers in fabricating mineralized PCL/ECM composite scaffolds. The presence of mineralized matrix induced the osteogenic differentiation of MSCs even in the absence of dexamethasone, and a more mature matrix with higher quantities of collagen and minerals improved osteogenesis by accelerating alkaline phosphatase expression and matrix mineralization. To determine whether PCL/ECM scaffolds can be applied to support the chondrogenic differentiation of MSCs, cartilaginous PCL/ECM composite scaffolds were fabricated. The presence of cartilaginous matrix reduced fibroblastic phenotype and in combination with transforming growth factor-β1 (TGF-β1), further promoted chondrogenesis as evident in elevated levels of glycosaminoglycan synthetic activity. While further investigation is necessary to optimize and test these scaffolds to induce the regeneration of cartilage and bone, this work demonstrates the importance of harnessing signals present in the native microenvironment to modulate chondrogenic and osteogenic differentiation.","abstract_has_math":false,"creators":["Liao, Jiehong"],"institution":"Rice University","degree_name":"Doctor of Philosophy","degree_level":"Doctoral","degree_discipline":"Engineering","degree_department":null,"school":null,"contributors":[],"advisors":["Mikos, Antonios G."],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011","date_published":"2011","updated_at":"2026-07-24T04:10:39Z","subjects":["Applied sciences","Tissue engineering","Stem cells","Extracellular matrix","Electrospinning","Biomedical engineering"],"languages":["eng"],"rights":["Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1911/70319","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Mikos, Antonios G."]},{"key":"dc:creator","label":"Author","values":["Liao, Jiehong"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2013-03-08T00:35:55Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2013-03-08T00:35:55Z"]},{"key":"dc:date.issued","label":"Date","values":["2011"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Rice University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Applied sciences","Tissue engineering","Stem cells","Extracellular matrix","Electrospinning","Biomedical engineering"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright is held by the author, unless otherwise indicated. 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In this work, signals present in the native microenvironment were utilized in fabricating polymer/extracellular matrix composite scaffolds to guide chondrogenic and osteogenic differentiation. In an osteochondral defect environment, interactions exist between bone marrow cell populations. Although MSCs have been extensively utilized for their ability to support hematopoietic stem and progenitor cells (HSPCs), the role of HSPCs in regulating the osteogenic differentiation of MSCs in the bone marrow niche is not well understood, and thus was explored via direct contact co-culture. HSPCs in a low dose with sustained osteogenic induction by dexamethasone accelerated osteogenesis and enhanced mineral deposition, whereas the lack of induction signals affected the spatial distribution of cell populations and minerals. Thus, HSPCs presumably play an active role in modulating the development and maintenance of the osteogenic niche. Since physical signals affect cellular activity, flow perfusion culture was employed to deposit mineralized extracellular matrix (ECM) with different maturity and composition on electrospun poly([varepsilon]-caprolactone) (PCL) microfibers in fabricating mineralized PCL/ECM composite scaffolds. The presence of mineralized matrix induced the osteogenic differentiation of MSCs even in the absence of dexamethasone, and a more mature matrix with higher quantities of collagen and minerals improved osteogenesis by accelerating alkaline phosphatase expression and matrix mineralization. To determine whether PCL/ECM scaffolds can be applied to support the chondrogenic differentiation of MSCs, cartilaginous PCL/ECM composite scaffolds were fabricated. The presence of cartilaginous matrix reduced fibroblastic phenotype and in combination with transforming growth factor-β1 (TGF-β1), further promoted chondrogenesis as evident in elevated levels of glycosaminoglycan synthetic activity. While further investigation is necessary to optimize and test these scaffolds to induce the regeneration of cartilage and bone, this work demonstrates the importance of harnessing signals present in the native microenvironment to modulate chondrogenic and osteogenic differentiation."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Modulation of Chondrogenic and Osteogenic Differentiation of Mesenchymal Stem Cells through Signals in the Extracellular Microenvironment"]}]}],"canonical_facts":{"dc:contributor.advisor":["Mikos, Antonios G."],"dc:creator":["Liao, Jiehong"],"dc:date.accessioned":["2013-03-08T00:35:55Z"],"dc:date.available":["2013-03-08T00:35:55Z"],"dc:date.issued":["2011"],"dc:description.abstract":["Damage to synovial joints results in osteochondral defects that only heal with inferior fibrous repair tissue. Since mesenchymal stem cells (MSCs) play a vital role in the natural development, maintenance, and repair of cartilage and bone, tissue engineering strategies to enhance functional regeneration by modulating MSC differentiation are a promising alternative to the limitations and potential complications associated with current conventional therapies. In this work, signals present in the native microenvironment were utilized in fabricating polymer/extracellular matrix composite scaffolds to guide chondrogenic and osteogenic differentiation. In an osteochondral defect environment, interactions exist between bone marrow cell populations. Although MSCs have been extensively utilized for their ability to support hematopoietic stem and progenitor cells (HSPCs), the role of HSPCs in regulating the osteogenic differentiation of MSCs in the bone marrow niche is not well understood, and thus was explored via direct contact co-culture. HSPCs in a low dose with sustained osteogenic induction by dexamethasone accelerated osteogenesis and enhanced mineral deposition, whereas the lack of induction signals affected the spatial distribution of cell populations and minerals. Thus, HSPCs presumably play an active role in modulating the development and maintenance of the osteogenic niche. Since physical signals affect cellular activity, flow perfusion culture was employed to deposit mineralized extracellular matrix (ECM) with different maturity and composition on electrospun poly([varepsilon]-caprolactone) (PCL) microfibers in fabricating mineralized PCL/ECM composite scaffolds. The presence of mineralized matrix induced the osteogenic differentiation of MSCs even in the absence of dexamethasone, and a more mature matrix with higher quantities of collagen and minerals improved osteogenesis by accelerating alkaline phosphatase expression and matrix mineralization. To determine whether PCL/ECM scaffolds can be applied to support the chondrogenic differentiation of MSCs, cartilaginous PCL/ECM composite scaffolds were fabricated. The presence of cartilaginous matrix reduced fibroblastic phenotype and in combination with transforming growth factor-β1 (TGF-β1), further promoted chondrogenesis as evident in elevated levels of glycosaminoglycan synthetic activity. While further investigation is necessary to optimize and test these scaffolds to induce the regeneration of cartilage and bone, this work demonstrates the importance of harnessing signals present in the native microenvironment to modulate chondrogenic and osteogenic differentiation."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/1911/70319"],"dc:language.iso":["eng"],"dc:rights":["Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder."],"dc:subject":["Applied sciences","Tissue engineering","Stem cells","Extracellular matrix","Electrospinning","Biomedical engineering"],"dc:title":["Modulation of Chondrogenic and Osteogenic Differentiation of Mesenchymal Stem Cells through Signals in the Extracellular Microenvironment"],"dc:type":["Thesis"],"thesis:degree_discipline":["Engineering"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Rice University"]},"updated_at":"2026-07-24T04:10:39Z"}