Looking Ahead: The Bio-Artificial Kidney

Transcription

1 Looking Ahead: The Bio-Artificial Kidney Teja Guda, PhD Assistant Professor, Department of Biomedical Engineering Assistant Director, Center for Innovation Technology and Entrepreneurship University of Texas at San Antonio April 27 th, 2017

2 The need for alternatives Chronic Kidney Disease 11% of adults 122k people on organ transplant waitlists : 101k of them for kidneys Wait time 3.6 years 3000 new/month in 2014 Montserrat et al,2016, FEBS Journal, 283:

3 Moon et al,2016, Methods, 99: Tissue Engineered Kidneys

4 What is the dream? TED Talk in 2011 Article in 2013 Please stop with the its possible to 3D print (x) articles So what are we doing about it?

5 Where are we now? How much necessary? Getting There Waiting on it Can Do! Can Do! Murphy & Atala,2014, Nature Biotechnology, 32:773-85

6 3D Printing in Kidneys? Hollow Organs Murphy & Atala,2014, Nature Biotechnology, 32:773-85

7 Strategies going forward Decellularization - Recellularization Rat Kidney Perfused with mescs Perfusion culture for 72 Hours Lin et al,2016, Cytotherapy, 18: Bonandrini et al, 2014, Tissue Engineering A, 20:

8 Considerations Availability of donor kidneys Appropriate cell type for re-cellularization Function

9 Bio-Printing Technology : Platforms for clinical translation Bio-mimicry Patient s own cells : Reprogramming? Function?

10 Maxillofacial Injuries Multiple fragments of bone Comminuted fracture + injury Immediately post surgery

11 Follow-up What are the concerns

12 What are the steps to getting there? Materials Mechanical properties Stability Cellular migration Transport properties Nutrient supply Material: Cells Scaffold Tissue specific cells Stem cells Chemical environment Differentiation signals Degradation products Immune response Biological: Progenitor Cells Chemical: Growth Factors

13 Diseases in the cross-hairs The buzzword is immune engineering Hunt, Biotechnol Lett, 2010

14 Complexity with Kidney Architecture Location of cells Cell phenotypes: Level of differentiation Ability to regenerate Stem cell origin High degree of vascularization

15 Mini-organs? Organoids Credit: Illustration by Claire Welsh/Nature

16 Printing technology

17 Visualization for surgery planning Komai et al, 2014, Urology, 83:

18 3D printed models for Patient Education Bernhard et al, 2016, World J Urol, 34:

19 3D printed models for surgery Donor Replica Recipient Model Image Guided Laparoscopy Optical Projection Tomography Kusaka et al, 2015, Transplantation Proceedings, 47: Creating a 3D Model Ureteric Tree

20 Bio-printing Low temperature Low pressure

21 Hunt, Biotechnol Lett, 2010 So we need an ink?

22 Cell encapsulation has been around Chondrocytes in 3D culture Flat mono-layer culture Spheroidal culture Ma, JBMR-A, 2002

23 Cell encapsulation Modular microencapsulation

24 Increased level of complexity Co-culture systems Cell type A Cell type B

25 Double Encapsulation Different cells and materials in different layers Differing levels of protection

26 Luo and Chen, Soft, 2012, Really, really, really complex

27 Use of microencapsulation Tissue Organoids Personalized Medicine Disease Modeling Drug Screening Cell delivery Improve retention Improve survival Provide protection Tissue regeneration Drug delivery Maintain space Improve transport properties Moyer, Annals Plastic Surgery, 2010

28 Kidney Organoids Morizane and Bonventre, Trends in Molecular Medicine, 2017,

29 Cell encapsulation applications Chitosan based beads for cell loading with growth factor delivery A Microbeaded tubes for regeneration of tubular secretory organs C D B

30 How have we moved forward again? Use Decellularization-Recellularization to model cell function Use 3D organoids to generate differentiated cells Study personalized drug sensitivity Use for broad therapy screening Identify self-assembly potential Learn about early kidney development

31 Basu and Ludlow, 2010, Trends in Biotechnology,28: Regenerative directions

32 Pati et al, 2014, Nature Communications, 5: 3935 Finally cell printing

33 Re-introducing cells for grafting

34 Wilm et al, 2016, Current Transplant Rep, 3: Revisiting the cell side Renal Organoids: - Self Organizing - Poor filtration - Low Translation Recellularization: - Perfect architecture - Low infiltration - High Translation Bioprinting: - Matrix + Cells - Differentiation? - Low Translation

35 Mimicking morphology - Vascularization Filtration Vascularization Complex branched connected architecture Bonandrini et al, 2014, Tissue Engineering A, 20:

36 Vascularization

37 Kolesky et al, 2014, Advanced Materials, 26: Critical Importance of Vasculature Paulsen and Miller, 2015, Developmental Dynamics, 244:

38 Haman et al, 2016, Nature Scientific Reports, 6:34845 Success stories Step By Step

39 Bioprinting Renal Proximal Tubules Jennifer Lewis Group, Wyss Institute, Harvard University

40 Engineering solutions sometimes not what one expects! 3D Heart LVAD

41 Questions?