Hang Lin

Assistant Professor
Assistant Professor
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Biography

Education and Training

  • Postdoctoral Associate, University of Pittsburgh School of Medicine, Pittsburgh, PA
  • Fellow, National Institutes of Health, Bethesda, MD
  • PhD, Cell Biology, Chinese Academy of Sciences, Beijing, P.R.CHINA
  • BS, Biochemistry, Nanjing University, Nanjing, P.R.CHINA

Research Interests

My research interests are to study the pathogenesis of osteoarthritis (OA) and develop disease modifying OA drugs. I am also interested in repairing articular cartilage through regenerative medicine strategy.

  1.  We have pioneered the development a human microphysiological knee joint chip, which is composed with cartilage, bone, fat pad and synovial membrane. We use this robust system to study OA pathogenesis and pain, as well as develop disease modifying OA drugs.
  2. We have for the first time applied a visible light-based stereolithographic method (VL-PSL,3D printing) to fabricate live cell-laden hydrogel scaffolds with customized geometry and internal architecture for tissue/organ regeneration. We have also developed an innovative visible light-based photo-crosslinking method to quickly fabricate hydrogel scaffolds in situ, with natural or synthesized biomaterials. We are also modifying chondroinducing medium, as well as modulating the relevant signaling pathways to induce chondrocyte, MSCs or iPSCs to regenerate hyaline cartilage for the repair of chondral injury.
  3. We are also conducting mechanistic study to understand the signaling pathways that mediate the influence of aging and mechanical overloading on chondrocyte.  

Representative Publications

  1. He Y, Makarczyk MJ, Lin H (corresponding author). Role of Mitochondria in Mediating Chondrocyte Response to Mechanical Stimuli. Life Sciences. 2020.
  2. Zhang X, Liu Y, Clark KL, Padget AM, Alexander PG, Dai J, Zhu W, Lin H (corresponding author). Mesenchymal stem cell-derived extracellular matrix (mECM): a bioactive and versatile scaffold for musculoskeletal tissue engineering. Biomedical Materials. 2020.
  3. Romero-López M, Li Z, Rhee C, Maruyama M, Pajarinen J, O'Donnell B, Lin TH, Lo CW, Hanlon J, Dubowitz R, Yao Z, Bunnell BA, Lin H, Tuan RS, Goodman SB. Macrophage Effects on Mesenchymal Stem Cell Osteogenesis in a Three-Dimensional In Vitro Bone Model. Tissue Engineering - Part A. 2020.
  4. He Y, Li Z, Alexander PG, Ocasio-Nieves BD, Yocum L, Lin H (corresponding author), Tuan RS. Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models. Biology (Basel). 2020;9(8):E194.
  5. Sun K, Lin H (co-first author), Tang Y, Xiang S, Tan J, Tuan RS, Wang B. Injectable BMP-2 gene-activated scaffold for the repair of cranial bone defect in mice. Stem Cells Translational Medicine. 2020 (In press).   
  6. Li L, Xiang S, Wang B, Lin H, Kihara S, Sun H, Alexander PG, Tuan RS. TGF-β1 plays a protective role in glucocorticoid-induced dystrophic calcification. Bone. 2020 Apr 4:115355.
  7. Shen H, Lin H, Sun AX, Song S, Wang B, Yang Y, Dai J, Tuan RS. Acceleration of chondrogenic differentiation of human mesenchymal stem cells by sustained growth factor release in 3D graphene oxide incorporated hydrogels. Acta Biomater. 2020 105:44-55.
  8. Lin Z, Li E, Li X, Del Duke CJ, Shen H, Hao T, Bunnell BA, Goodman SB, Alexander PG, Tuan RS, Lin H (corresponding author). Osteochondral Tissue Chip Derived from iPSCs: Modeling OA Pathologies and Testing Drugs. Frontiers in Bioengineering and Biotechnology. 2019, 7:411.
  9. Kuang B, Yang Y, Lin H (corresponding author). Infiltration and In-Tissue Polymerization of Photocross-Linked Hydrogel for Effective Fixation of Implants into Cartilage—An In Vitro Study. ACS Omega. 2019 4, 20, 18540-18544
  10. Yang Y, Liu Y, Lin Z, Shen He, Lucas C, Kuang B, Tuan RS, Lin H (corresponding author). Condensation-driven Chondrogenesis of Human Mesenchymal Stem Cells Within Their Own Extracellular Matrix: Formation of Cartilage with Low Hypertrophy and Physiologically Relevant Mechanical Properties. Advanced Biosystems. 2019 3(12):e1900229 (Front Cover).
  11. Lin H, Tang Y, Lozito TP, Oyster N, Wang B, Tuan RS. Efficient in vivo Bone Formation by BMP-2 Engineered Human Mesenchymal Stem Cells Encapsulated in a Projection Stereolithographically Fabricated Hydrogel Scaffold. Stem Cell Res Ther. 2019. 10(1):254.
  12. Liu Y, Kuang B, Rothrauff BB, Tuan RS, Lin H (corresponding author). Robust bone regeneration through endochondral ossification of human mesenchymal stem cells within their own extracellular matrix. Biomaterials. 2019, Jul 6;218:119336.
  13. Moncada-Saucedo NK, Marino-Martínez IA, Lara-Arias J, Romero-Díaz VJ, Camacho A, Valdés-Franco JA, Pérez-Silos V, García-Ruiz A, Lin H, Tuan RS, Ramos-Payán R, Lara-Banda M, Ortiz-Lopez R, Rojas-Martinez A, Fuentes-Mera L. A Bioactive Cartilage Graft of IGF1-Transduced Adipose Mesenchymal Stem Cells Embedded in an Alginate/Bovine Cartilage Matrix Tridimensional Scaffold. Stem Cells Int. 2019:9792369.
  14. Lin H (corresponding author), Beck AM, Shimomura K, Sohn J, Fritch MR, Deng Y, Kilroy EJ, Tang Y, Alexander PG, Tuan RS. Optimization of Photocrosslinked Gelatin/Hyaluronic Acid Hybrid Scaffold for the repair of cartilage defect. J Tissue Eng Regen Med. 2019 (Epub ahead of print).
  15. Deng Y, Lei G, Lin Z, Yang Y, Lin H (corresponding author), Tuan RS. Engineering hyaline cartilage from mesenchymal stem cells with low hypertrophy potential via modulation of culture conditions and Wnt/β-catenin pathway. Biomaterials. 2019, 192:569-578.
  16. Deng Y, Sun AX, Overholt KJ, Yu GZ, Fritch MR, Alexander PG, Shen H, Tuan RS, Lin H (corresponding author). Enhancing chondrogenesis and mechanical strength retention in physiologically relevant hydrogels with incorporation of hyaluronic acid and direct loading of TGF-β. Acta Biomater. 2019, 83:167-176.
  17. Lin H, Sohn J, Langhans MT, Shen H, Tuan RS. Bone Marrow Mesenchymal Stem Cells: Aging and Tissue Engineering Applications to Enhance Bone Healing. Biomaterials, 2018, S0142-9612(18)30447-2. 
  18. Sohn J, Lin H, Fritch MR, Tuan RS. Influence of cholesterol/caveolin-1/caveolae homeostasis on membrane properties and substrate adhesion characteristics of adult human mesenchymal stem cells. Stem Cell Res Ther. 2018, 9:86.
  19. Yang Y, Lin H (co-first author), Shen H, Wang B, Lei GH, Tuan RS. Mesenchymal Stem Cell-Derived Extracellular Matrix Enhances Chondrogenic Phenotype of and Cartilage Formation by Encapsulated Chondrocytes in vitro and in vivo. Acta Biomaterialia, 2018, 69:71-82.
  20. Shen H, Lin H, Sun AS, Song SJ, Zhang ZJ, Dai JW, Tuan RS. Chondroinductive Factor-Free Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Graphene Oxide- Incorporated Hydrogels. Journal of Materials Chemistry B, 2018, 6, 908 - 91.
  21. Lin H, Tang Y, Lozito TP, Oyster N, Kang RB, Fritch MR, Wang B, Tuan RS.  Projection Stereolithographic Fabrication of BMP-2 Gene-activated Matrix for Bone Tissue Engineering. Scientific Reports, 2017, 7, 11327.
  22. Xue J, Lin H, Bean A, Tang Y, Tan J, Tuan RS, Wang B. One-Step Fabrication of Bone Morphogenetic Protein-2 Gene Activated, Porous Poly-L-Lactide Scaffold for Bone Induction. Molecular Therapy — Methods & Clinical Developments, 2017, 7, 50-59.
  23. Sun AX, Lin H, Fritch MR, Shen H, Alexander PG, DeHart M, Tuan RS, Chondrogenesis of Human Bone Marrow Mesenchymal Stem Cells in 3-Dimensional, Photocrosslinked Hydrogel Constructs: Effect of Cell Seeding Density and Material Stiffness. Acta Biomaterialia, 2017, 58,302-11.
  24. Blair HC, Larrouture QC, Li YN, Lin H, Beer-Stoltz D, Liu L, Tuan RS, Robinson LJ, Schelsinger PH, Nelson DJ . Osteoblast Differentiation and Bone Matrix Formation In Vivo  and In Vitro. Tissue engineering-B, 2017, 23(3): 1-13.
  25. Yang G, Lin H, Rothrauff BB, Yu S, Tuan RS. (2016) Multilayered polycaprolactone/gelatin fiber-hydrogel composite for tendon tissue engineering. Acta Biomater. 15;35:68-76.
  26. Sun AX, Lin H (co-first author), Beck AM, Kilroy EJ, Tuan RS. (2015) Projection Stereolithographic Fabrication of Human Adipose Stem Cell-incorporated Biodegradable Scaffolds for Cartilage Tissue Engineering. Frontiers in Bioengineering and Biotechnology, 2015.
  27. Lin H, Lozito TP, Alexander PG, Gottardi R, Tuan RS. Stem Cell-based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β. Molecular Pharmaceutics, 2014, 11(7):2203-12.
  28. Lin H, Cheng AWM, Alexander P, Bech AM, Tuan RS. Cartilage Tissue Engineering Application of Injectable Gelatin Hydrogel with in situ Visible Light-Activated Gelation Capability in Both Air and Aqueous Solution. Tissue Engineering-A, 2014, 20 (17-18): 2402-11.
  29. Lin H, Zhang DN, Alexander P, Yang G, Tan J, Cheng AWM, Tuan RS. The Application of Visible Light-based Projection Stereolithography (VL-PSL) in Live Cell-Scaffold Fabrication with Designed Architecture. Biomaterials 2013, 34(2):331-9
  30. Lin H, Yang G, Tan J, Tuan RS. Influence of Decellularized Matrix Derived from Human Mesenchymal Stem Cells on Their Proliferation, Migration and Multi-lineage Differentiation Potential. Biomaterials 2012, 33(18):4480-9.

Pubmed link

Research Grants

Tissue Chip Modeling of Synovial Joint Pathologies: Effects of Inflammation and Adipose-Mediated Diabetic Complications
Project period: 07/01/2019-06/30/2022
Sponsor: NIH-UH3
Role: PI

Joint Pain on a Chip: Mechanistic Analysis Therapeutic Targets and an Empirical Strategy for Personalized Pain Management.
Project period: 9/01/19-08/31/2021
Sponsor: NIH-UG3
Role: MPI

Tissue Chip Modeling of Acute and Chronic Pain in Osteoarthritis  
Project period: 10/01/2020-09/30/2023
Sponsor: DoD
Role: PI

Degrees

  • PhD