Table 3. Materials Design Pillar Timelines of Activities, Milestones, Metrics, and Anticipated Outcomes Goal 1.1: Selec Objectiv Objectiv Objective 1.1a tion of optimal hard e 1.1a: Design and e 1.1b: Characterize CCBSE RESmaterials as porou optimize nanoclay the scaffolds and EARCH GOALS: Materials Design Pillar s bone-mimetic scaffolds scaffolds demonstrate cancer cell growth Specific milestones Year 1 Year 2 Year 3 Year 4 Year 5 Responsible parties Activity 1: Prepare nanoclay scaffolds with amino acids for cancer cell growth Activity 2: Assist non-RU campuses involved in Activity 1 with compliance protocols Prepare scaffolds based on prior studies Assist with the initiation of conversations between non-RU faculty and RU campuses for the administration of necessary compliance protocols (IBC, MTAs) [Approved by NSF on 7/28/21] Optimize amino acid structure based on modeling, the loading amount, prepare two additional scaffolds, provide scaffolds to nanomaterials sub-group and Cellular Systems Pillar Ensure that all necessary compliance protocols are in place at the non- RU campuses [Approved by NSF on 7/28/21] Provide feedback to the Computational Approaches Pillar, optimize scaffold materials, provide the scaffolds for nanomaterials testing Ensure that all necessary compliance protocols are in place at the non- RU campuses [Approved by NSF on 7/28/21] Continue to prepare the optimized scaffold, provide them to Cellular Systems Pillar Ensure that all necessary compliance protocols are in place at the non-RU campuses [Approved by NSF on 7/28/21] Continue to prepare the optimized scaffold Ensure that all necessary compliance protocols are in place at the non-RU campuses [Approved by NSF on 7/28/21] Lead: ▇. ▇▇▇▇▇, Co-lead: ▇. ▇▇, ▇. ▇▇▇, (Computational Approaches Pillar liaison), New Hire at NDSU [Approved by NSF 9/8/21] Leads: ▇. ▇▇▇▇▇, ▇. ▇▇▇▇▇, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇ Activity 1: Mechanical Continue with Optimize scaffold Continue to prepare Continue to prepare Lead: ▇. ▇▇▇▇▇ Characterize characterization, characterization, and cancer cell the optimized the optimized Co-lead: G. the scaffolds biocompatibility optimize cell growth conditions, scaffolds with scaffolds with cancer ▇▇, ▇. ▇▇▇ and culture of testing, spheroid growth, nanomechanics cancer cells and cells and patient- (Computational breast and nanomechanics, nanomechanics patient-derived derived samples Approaches prostate metastatic samples Pillar liaison), cancer cells breast and New Hire at prostate growth NDSU [Approved by NSF 9/8/21] Goal 1.2: Selection of optimal polymeric materials as soft tissue-mimetic scaffolds • Objective 1.2a: Design and optimize soft polymeric scaffolds • Objective 1.2b: Characterize the scaffolds and demonstrate cancer cell growth Activity 1: Prepare soft Optimize the Based on the Continue to prepare Continue to prepare Lead: ▇. ▇▇▇▇▇, Prepare soft material scaffolds scaffolds by feedback from the the optimized the optimized ▇. ▇▇▇▇▇▇▇ scaffolds from from two polymers altering the Computational scaffolds, provide scaffolds, provide Co-leads: M. ▇▇▇, ▇▇▇, and polymer Approaches and scaffolds for scaffolds for ▇▇▇▇▇▇, B. PgA, composition and Cellular Systems nanomaterials nanomaterials Voels, M. characterize the molecular Pillars optimize testing and Cellular testing and Cellular ▇▇▇▇▇▇, ▇. scaffolds weights, provide scaffold materials, Systems Pillar Systems Pillar ▇▇▇▇▇▇, ▇. ▇▇▇ feedback to Computational Approaches Pillar provide scaffolds for nanomaterials testing and Cellular (Computational Approaches Pillar liaison) and scaffolds for Systems Pillar nanomaterials testing and Cellular Systems Pillar
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Sources: NSF Epscor Rii Track 1 Strategic Plan, NSF Epscor Rii Track 1 Strategic Plan
Table 3. Materials Design Pillar Timelines of Activities, Milestones, Metrics, and Anticipated Outcomes Goal 1.1: Selec Objectiv Objectiv Objective 1.1a tion of optimal hard e 1.1a: Design and e 1.1b: Characterize CCBSE RESmaterials as porou optimize nanoclay the scaffolds and EARCH GOALS: Materials Design Pillar s bone-mimetic scaffolds scaffolds demonstrate cancer cell growth Specific milestones Year 1 Year 2 Year 3 Year 4 Year 5 Responsible parties Activity 1: Prepare nanoclay scaffolds with amino acids for cancer cell growth Activity 2: Assist non-RU campuses involved in Activity 1 with compliance protocols [Metric change approved by NSF on 7/28/21] Prepare scaffolds based on prior studies Assist with the initiation of conversations between non-RU faculty and RU campuses for the administration of necessary compliance protocols (IBC, MTAs) [Approved by NSF on 7/28/21] Optimize amino acid structure based on modeling, the loading amount, prepare two additional scaffolds, provide scaffolds to nanomaterials sub-group and Cellular Systems Pillar Ensure that all necessary compliance protocols are in place at the non- RU campuses [Approved by NSF on 7/28/21] Provide feedback to the Computational Approaches Pillar, optimize scaffold materials, provide the scaffolds for nanomaterials testing Ensure that all necessary compliance protocols are in place at the non- RU campuses [Approved by NSF on 7/28/21] Continue to prepare the optimized scaffold, provide them to Cellular Systems Pillar Ensure that all necessary compliance protocols are in place at the non-RU campuses [Approved by NSF on 7/28/21] Continue to prepare the optimized scaffold Ensure that all necessary compliance protocols are in place at the non-RU campuses [Approved by NSF on 7/28/21] Lead: ▇. ▇▇▇▇▇, Co-lead: ▇. ▇▇, ▇. ▇▇▇, (Computational Approaches Pillar liaison), New Hire at NDSU [Approved Responsibility change approved by NSF 9/8/21] Leads: ▇. ▇▇▇▇▇, ▇. ▇▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇ [Responsibility change approved by NSF on 5/16/22] Activity 1: Mechanical Continue with Optimize scaffold Continue to prepare Continue to prepare Lead: ▇. ▇▇▇▇▇ Characterize characterization, characterization, and cancer cell the optimized the optimized Co-lead: G. the scaffolds biocompatibility optimize cell growth conditions, scaffolds with scaffolds with cancer ▇▇, ▇. ▇▇▇ and culture of testing, spheroid growth, nanomechanics cancer cells and cells and patient- (Computational breast and nanomechanics, nanomechanics patient-derived derived samples Approaches prostate metastatic samples Pillar liaison), cancer cells breast and New Hire at prostate growth NDSU [Approved Responsibility change approved by NSF 9/8/21] Goal 1.2: Selection of optimal polymeric materials as soft tissue-mimetic scaffolds • Objective 1.2a: Design and optimize soft polymeric scaffolds • Objective 1.2b: Characterize the scaffolds and demonstrate cancer cell growth Activity 1: Prepare soft Optimize the Based on the Continue to prepare Continue to prepare Lead: ▇. ▇▇▇▇▇, Prepare soft scaffolds from Chi, Alg, and PgA, characterize the scaffolds material scaffolds from two polymers scaffolds by altering the polymer composition and molecular weights, provide feedback to Computational Approaches Pillar and scaffolds for nanomaterials testing and Cellular feedback from the Computational Approaches and Cellular Systems Pillars optimize scaffold materials, provide scaffolds for nanomaterials testing and Cellular the optimized scaffolds, provide scaffolds for nanomaterials testing and Cellular Systems Pillar the optimized scaffolds, provide scaffolds for nanomaterials testing and Cellular Systems Pillar ▇. ▇▇▇▇▇▇▇ scaffolds from from two polymers altering the Computational scaffolds, provide scaffolds, provide Co-leads: M. ▇▇▇, ▇▇▇, and polymer Approaches and scaffolds for scaffolds for ▇▇▇▇▇▇, B. PgA, composition and Cellular Systems nanomaterials nanomaterials Voels, M. characterize the molecular Pillars optimize testing and Cellular testing and Cellular . ▇▇▇▇▇▇, ▇. scaffolds weights▇▇▇▇▇, provide scaffold materials▇. ▇▇▇▇▇▇, Systems Pillar Systems Pillar ▇. ▇▇▇▇▇▇, ▇. ▇▇▇ feedback to Computational Approaches Pillar provide scaffolds for nanomaterials testing and Cellular (Computational Approaches Pillar liaison) Systems Pillar Systems Pillar Activity 2: Assist non- RU campuses involved in Activity 1 with compliance protocols [Metric change approved by NSF on 7/28/22] Assist with the initiation of conversations between non-RU faculty and RU campuses for the administration of necessary compliance protocols (IBC, MTAs) Ensure that all necessary compliance protocols are in place at the non- RU campuses Ensure that all necessary compliance protocols are in place at the non- RU campuses Ensure that all necessary compliance protocols are in place at the non-RU campuses Ensure that all necessary compliance protocols are in place at the non-RU campuses Leads: ▇. ▇▇▇▇▇, ▇. ▇▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇ [Responsibility change approved by NSF on 5/16/22} Activity 1: Determine mechanical properties, cell viability in the scaffolds, analyze gene expression profiles Mechanical characterization, nanomechanics, biocompatibility testing, breast and prostate cancer cell growth Continue with characterization, optimize tumoroid growth, nanomechanics Optimize scaffold and cancer cell growth conditions, nanomechanics Continue to prepare the optimized scaffolds with cancer cells Continue to prepare the optimized scaffolds with cancer cells Lead: ▇. ▇▇▇▇▇ Co-lead: ▇. ▇▇, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇▇▇▇, ▇. ▇▇▇ (Computational Approaches Pillar liaison) Activity 2: Assist non-RU campuses involved in Activity 1 with compliance protocols [Metric change approved by NSF on 7/28/21] Assist with the initiation of conversations between non-RU faculty and RU campuses for the administration of necessary compliance protocols (IBC, MTAs) Ensure that all necessary compliance protocols are in place at the non- RU campuses Ensure that all necessary compliance protocols are in place at the non-RU campuses Ensure that all necessary compliance protocols are in place at the non-RU campuses Ensure that all necessary compliance protocols are in place at the non-RU campuses Leads: ▇. ▇▇▇▇▇, ▇. ▇▇▇▇▇▇▇ n, ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇ [Responsibility change approved by NSF 5/16/22 Goal 1.3: Develop a system for vascular surrogacy in 3D co-cultures • Objective 1.3a: Design and develop stimuli-responsive polymeric materials as nanocarriers • Objective 1.3b: Design and develop silicon quantum dots (QDs) and polymer-QDs hybrids for bioimaging • Objective 1.3c: Design and test polymer nanoparticles for vascular surrogacy Activity 1: Investigate pH responsive properties Identify poly(silyl ether)s as pH- responsive materials Modify and improve polymer structure and nanoparticles (NPs) properties Make light- responsive polymeric materials for controlled release and optimize NPs fabrication Prepare lanthanide binding polymeric materials and fabricate NPs Prepare multi- responsive polymeric materials and fabricate NPs Lead: G. Du Co-leads: ▇. ▇▇▇▇, ▇. ▇▇▇▇▇, B. Sui [Responsibility change approved by NSF 7/28/21] Activity 2: Test biocompatibility Fabricate and characterize NPs Test toxicity of the polymers and NPs Test the cell survival rate when the light-responsive polymer Test biocompatibility of the lanthanide binding polymer NPs Evaluate polymer- NPs biocompatibility in vitro Lead: G. Du Co-leads: ▇. ▇▇▇▇, ▇. ▇▇▇▇▇, ▇. ▇▇▇ [Responsibility change approved by NSF 7/28/21] Activity 3: Examine cell culture usage Determine optimal hard and soft scaffolds in in vitro studies Determine optimal cancer cell identification using the polymer NPs in 3D cells Image 3D hard and soft scaffolds using the prepared NPs Determine cellular applications of the NPs in soft and hard scaffolds Lead: G. Du Co-leads: ▇. ▇▇▇▇, ▇. ▇▇▇▇▇, B. Sui [Responsibility change approved by NSF 7/28/21] Activity 1: Selection of the best precursor Selection of precursors for making silicon quantum dots (QDs) Modify quantum dot surface through chemical reactions Selection of polymer to improve quantum dot’s quantum yield Making quantum dot and polymer hybrids Prepare the optimized hybrid of quantum dots- polymer in 3D scaffold Lead: ▇. ▇▇▇▇ Co-leads: ▇. ▇▇, ▇. ▇▇▇▇▇, ▇. ▇▇▇ [Responsibility change approved by NSF on 7/28/21] Activity 2: Testing feasibility Optimization of QD’s optical signals in cancer cells Test toxicity and biocompatibility of the QDs Test the selected polymers in bioimaging Test the biocompatibility of hybrids in 3D cell Culture Identification of intra cellular reactions using the hybrids in soft and hard scaffold Lead: ▇. ▇▇▇▇ Co-leads: ▇. ▇▇, ▇. ▇▇▇▇▇, B. Sui [Responsibility change approved by NSF on 7/28/21] Activity 3: Cancer cells imaging Application of the QDs in cancer cell imaging Application of the QDs for cancer cell identification Application of the polymers in cancer cell imaging Application of the hybrids in 3D cell culture Application of the hybrids in 3D cell culture Lead: ▇. ▇▇▇▇ Co-leads: ▇. ▇▇, ▇. ▇▇▇▇▇, B. Sui [Responsibility change approved by NSF on 7/28/21] Activity 1: Design, preparation, and testing of hypoxia- responsive polymer nanoparticles Synthesize a set of diblock copolymers Optimize release properties of anticancer drugs using cancer cells on hard and soft material scaffolds Select the optimal nanoparticle, demonstrate tumor targeting and tumor penetration on the hard and soft material scaffolds Determine the effects of the released drugs on the cancer cells, mechanistic studies Based on the mechanistic studies, select and demonstrate the efficacy of the optimal variant Lead: ▇. ▇▇▇▇▇▇ Co-leads: ▇. ▇▇▇▇▇▇▇, ▇. ▇▇▇▇▇, ▇. ▇▇ [Responsibility change approved by NSF on 9/8/21] Activity 2: Design, preparation, and testing of pH-responsive polymer nanoparticles Synthesize a set of triblock copolymers with conjugated anticancer drugs Optimize pH- mediated release of the anticancer drugs Select the optimal nanoparticle, demonstrate tumor targeting and penetration on the hard and soft scaffolds Mechanistic studies on the pH-triggered drug release from polymer backbone, cellular effects of the released drugs Based on the mechanistic studies, select and demonstrate the efficacy of the optimal variant Lead: ▇. ▇▇▇▇▇▇ Co-leads: ▇. ▇▇▇▇▇▇, ▇. ▇▇▇▇▇, G. Du, New Hire at NDSU [Approved by NSF 9/8/21] Objective 1.1a [Metric change approved by NSF on 9/8/21] Prepare 3 different biocompatible scaffolds Develop 2 nanoclay scaffolds incorporating the amino acids and evaluate additional one hard scaffold Select one optimal scaffold (critical) Prepare enough scaffolds for Systems the other Pillars and for Materials Design Pillar nanomaterials testing Goal 3 Prepare enough scaffolds for the other Pillars and Cellular Systems Pillarfor Materials Design Pillar Goal 3
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