Skip to main content

Advertisement

SpringerLink
Log in

Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

  • Original Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering.

Methods

Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured.

Results

Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter.

Conclusions

Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Abbreviations

AA:

Ascorbic acid

HDIt:

Hexamethylene diisocyanate trimer

LTI:

Lysine triisocyanate

PDGF:

Platelet-derived growth factor

PEG:

Poly(ethylene glycol)

PUR:

Polyurethane

900:

900-MW trifunctional polyol of 60/30/10 ε-caprolactone/glycolide/lactide

1800:

1800-MW trifunctional polyol of 60/30/10 ε-caprolactone/glycolide/lactide

References

  1. American Academy of Orthopaedic Surgeons website (www.aaos.org).

  2. J. S. Temenoff, and A. G. Mikos. Injectable biodegradable materials for orthopedic tissue engineering. Biomaterials. 21:2405–2412 (2000).

    Article  PubMed  CAS  Google Scholar 

  3. P. Gunatillake, R. Mayadunne, R. Adhikari, and M. R. El-Gewely. Recent developments in biodegradable synthetic polymers. Biotechnol. Annu. Rev. 12:301–347 (2006)Elsevier.

    Article  PubMed  CAS  Google Scholar 

  4. S. L. Bourke, and J. Kohn. Polymers derived from the amino acid —tyrosine: polycarbonates, polyarylates and copolymers with poly(ethylene glycol). Adv. Drug Deliv. Rev. 55:447–466 (2003).

    Article  PubMed  CAS  Google Scholar 

  5. S. I. Ertel, and J. Kohn. Evaluation of a series of tyrosine-derived polycarbonates as degradable biomaterials. J. Biomed. Materi. Res. 28:919–930 (1994).

    Article  CAS  Google Scholar 

  6. C. Yu, and J. Kohn. Tyrosine-PEG-derived poly(ether carbonate)s as new biomaterials: part I: synthesis and evaluation. Biomaterials. 20:253–264 (1999).

    Article  PubMed  CAS  Google Scholar 

  7. A. D. Augst, H.-J. Kong, and D. J. Mooney. Alginate hydrogels as biomaterials. Macromol. Biosci. 6:623–633 (2006).

    Article  PubMed  CAS  Google Scholar 

  8. R. R. Chen, and D. J. Mooney. Polymeric growth factor delivery strategies for tissue engineering. Pharm. Res. 20:1103–1112 (2003).

    Article  PubMed  CAS  Google Scholar 

  9. N. Kipshidze, P. Chawla, and M. H. Keelan. Fibrin Meshwork as a Carrier for Delivery of Angiogenic Growth Factors in Patients With Ischemic Limb. Mayo Clin. Proc. 74:47–848 (1999).

    Google Scholar 

  10. V. Labhasetwar, J. Bonadio, S. Goldstein, W. Chen, and R. J. Levy. A DNA controlled-release coating for gene transfer: transfection in skeletal and cardiac muscle. J. Pharm. Sci. 87:1347–1350 (1998).

    Article  PubMed  CAS  Google Scholar 

  11. K. Mizuno, K. Yamamura, K. Yano, T. Osada, S. Saeki, N. Takimoto, T. Sakurai, and Y. Nimura. Effect of chitosan film containing basic fibroblast growth factor on wound healing in genetically diabetic mice. J. Biomed. Materi. Res. A. 64A:177–181 (2003).

    Article  CAS  Google Scholar 

  12. C. A. Simmons, E. Alsberg, S. Hsiong, W. J. Kim, and D. J. Mooney. Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. Bone. 35:562–569 (2004).

    Article  PubMed  CAS  Google Scholar 

  13. S. A. Zawko, Q. Truong, and C. E. Schmidt. Drug-binding hydrogels of hyaluronic acid functionalized with β-cyclodextrin. J. Biomed. Materi. Res. A 9999:NA (2008).

    Google Scholar 

  14. M. D. Timmer, C. G. Ambrose, and A. G. Mikos. Evaluation of thermal- and photo-crosslinked biodegradable poly(propylene fumarate)-based networks. J. Biomed. Materi. Res. A. 66A:811–818 (2003).

    Article  CAS  Google Scholar 

  15. C. W. Kim, R. Talac, L. Lu, M. J. Moore, B. L. Currier, and M. J. Yaszemski. Characterization of porous injectable poly-(propylene fumarate)-based bone graft substitute. J. Biomed. Materi. Res. A 9999:NA (2007).

    Google Scholar 

  16. J. P. Fisher, J. W. M. Vehof, D. Dean, J. P. van der Waerden, T. A. Holland, A. G. Mikos, and J. A. Jansen. Soft and hard tissue response to photocrosslinked poly(propylene fumarate) scaffolds in a rabbit model. J. Biomed. Materi. Res. 59:547–556 (2002).

    Article  CAS  Google Scholar 

  17. S. J. Peter, L. Lu, D. J. Kim, and A. G. Mikos. Marrow stromal osteoblast function on a poly(propylene fumarate)/[beta]-tricalcium phosphate biodegradable orthopaedic composite. Biomaterials. 21:1207–1213 (2000).

    Article  PubMed  CAS  Google Scholar 

  18. S. J. Peter, S. T. Miller, G. Zhu, A. W. Yasko, and A. G. Mikos. In vivo degradation of a poly(propylene fumarate)/β-tricalcium phosphate injectable composite scaffold. J. Biomed. Materi. Res. 41:1–7 (1998).

    Article  CAS  Google Scholar 

  19. M. J. Yaszemski, R. G. Payne, W. C. Hayes, R. S. Langer, T. B. Aufdemorte, and A. G. Mikos. The ingrowth of new bone tissue and initial mechanical properties of a degrading polymeric composite scaffold. Tissue Eng. 1:41–52 (1995).

    Article  CAS  Google Scholar 

  20. D. H. R. Kempen, L. Lu, C. Kim, X. Zhu, W. J. A. Dhert, B. L. Curreir, and M. J. Yaszemski. Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate). J. Biomed. Materi. Res. A. 77A:103–111 (2006).

    Article  CAS  Google Scholar 

  21. I. C. Bonzani, R. Adhikari, S. Houshyar, R. Mayadunne, P. Gunatillake, and M. M. Stevens. Synthesis of two-component injectable polyurethanes for bone tissue engineering. Biomaterials. 28:423–433 (2007).

    Article  PubMed  CAS  Google Scholar 

  22. K. Gorna, and S. Gogolewski. Preparation, degradation, and calcification of biodegradable polyurethane foams for bone graft substitutes. J. Biomed. Materi. Res. A. 67A:813–827 (2003).

    Article  CAS  Google Scholar 

  23. S. Guelcher, A. Srinivasan, A. Hafeman, K. Gallagher, J. Doctor, S. Khetan, S. McBride, and J. Hollinger. Synthesis, in vitro degradation, and mechanical properties of two-component poly(ester urethane)urea scaffolds: effects of water and polyol composition. Tissue Eng. 13:2321–2333 (2007).

    Article  PubMed  CAS  Google Scholar 

  24. J.-Y. Zhang, E. J. Beckman, J. Hu, G.-G. Yang, S. Agarwal, and J. O. Hollinger. Synthesis, biodegradability, and biocompatibility of lysine diisocyanate-glucose polymers. Tissue Eng. 8:771–785 (2002).

    Article  PubMed  CAS  Google Scholar 

  25. R. Adhikari and P. A. Gunatillake. Biodegradable polyurethane/urea compositions. (2004).

  26. M. Kitai, H. Ryuutou, T. Yahata, Y. Hara, H. Iwane, and Y. Soejima. Aliphatic triisocyanate compound, process for producing the same, and polyurethane resin made from the compound. In U. PTO (ed), Vol. 20020123644 A1 (U. PTO, ed) (2002).

  27. S. A. Guelcher, V. Patel, K. M. Gallagher, S. Connolly, J. E. Didier, J. S. Doctor, and J. O. Hollinger. Synthesis and in vitro biocompatibility of injectable polyurethane foam scaffolds. Tissue Eng. 12:1247–1259 (2006).

    Article  PubMed  CAS  Google Scholar 

  28. A. S. Sawhney, and J. A. Hubbell. Rapidly degraded terpolymers of D,L-lactide, glycolide, and ε-caprolactone with increased hydrophilicity by copolymerization with polyethers. J. Biomed. Mater. Res. 24:1397–1411 (1990).

    Article  PubMed  CAS  Google Scholar 

  29. ASTM-International. D3574–05. Standard test methods for flexible cellular materials-slab, bonded, and molded urethane foams. 08.02:360–368 (2007).

  30. G. Evans, B. Atkinson, and G. Jameson. The Jameson cell. In K. Matis (ed.), Flotation Science and Engineering, Marcel Dekker, New York, 1995, p. 353.

    Google Scholar 

  31. ASTM-International. D695–02a. Standard test method for compressive properties of rigid plastics. 14.02 (2007).

  32. G. Oertel. Polyurethane Handbook. Hanser Gardner Publications, Berlin, 1994.

    Google Scholar 

  33. R. Eriksson, T. Albrektsson, and B. Magnusson. Assessment of bone viability after heat trauma. A histological, histochemical and vital microscopic study in the rabbit. Scand. J. Plast. Reconstr. Surg. 18:261–268 (1984).

    Article  PubMed  CAS  Google Scholar 

  34. P. J. Meyer, E. Lautenschlager, and B. Moore. On the setting properties of acrylic bone cement. J. Bone Jt. Surg. 55:149–156 (1973).

    Google Scholar 

  35. J. E. Mark, E. Erman, and F. R. Eirich. Science and Technology of Rubber. Academic Press, Inc., San Diego, CA, 1994.

    Google Scholar 

  36. O. Kramer, S. Hvidt, and J. D. Ferry. Dynamic mechanical properties. In J. E. Mark, E. Erman, and F. R. Eirich (eds.), Science and Technology of Rubber, Academic Press, Inc., San Diego, CA, 1994.

    Google Scholar 

  37. S. Gogolewski, K. Gorna, and A. S. Turner. Regeneration of bicortical defects in the iliac crest of estrogen-deficient sheep, using new biodegradable polyurethane bone graft substitutes. J. Biomed. Mater. Res. A. 77A:802–810 (2006).

    Article  CAS  Google Scholar 

  38. J. Guan, K. L. Fujimoto, M. S. Sacks, and W. R. Wagner. Preparation and characterization of highly porous, biodegradable polyurethane scaffolds for soft tissue applications. Biomaterials. 26:3961–3971 (2005).

    Article  PubMed  CAS  Google Scholar 

  39. J.-Y. Zhang, E. J. Beckman, N. P. Piesco, and S. Agarwal. A new peptide-based urethane polymer: synthesis, biodegradation, and potential to support cell growth in vitro. Biomaterials. 21:1247–1258 (2000).

    Article  PubMed  CAS  Google Scholar 

  40. J. H. de Groot, R. de Vrijer, B. S. Wildeboer, C. S. Spaans, and A. J. Pennings. New biomedical polyurethane ureas with high tear strengths. Polym. Bull. 38:211–218 (1997).

    Article  Google Scholar 

  41. G. A. Skarja, and K. A. Woodhouse. Structure-property relationships of degradable polyurethane elastomers containing an amino acid-based chain extender. J. Appl. Polym. Sci. 75:1522–1534 (2000).

    Article  CAS  Google Scholar 

  42. N. Tsutsumi, S. Yoshizaki, W. Sakai, and T. Kiyotsukuri. Nonlinear optical polymers. 1. Novel network polyurethane with azobenzene dye in the main frame. Macromolecules. 28:6437–6442 (1995).

    Article  CAS  Google Scholar 

  43. S. Gogolewski, and K. Gorna. Biodegradable polyurethane cancellous bone graft substitutes in the treatment of iliac crest defects. J Biomed. Mater. Res. A. 80A:94–101 (2007).

    Article  CAS  Google Scholar 

  44. K. Gorna, and S. Gogolewski. Molecular stability, mechanical properties, surface characteristics and sterility of biodegradable polyurethanes treated with low-temperature plasma. Polym. Degrad. Stab. 79:475–485 (2003).

    Article  CAS  Google Scholar 

  45. K. Gorna, S. Polowinski, and S. Gogolewski. Synthesis and characterization of biodegradable poly(ε-caprolactone urethane)s. I. Effect of the polyol molecular weight, catalyst, and chain extender on the molecular and physical characteristics. J. Polym. Sci. A Polym. Chem. 40:156–170 (2002).

    Article  CAS  Google Scholar 

  46. J. Guan, M. S. Sacks, E. J. Beckman, and W. R. Wagner. Biodegradable poly(ether ester urethane)urea elastomers based on poly(ether ester) triblock copolymers and putrescine: synthesis, characterization and cytocompatibility. Biomaterials. 25:85–96 (2004).

    Article  PubMed  CAS  Google Scholar 

  47. P. Bruin, G. J. Veenstra, A. J. Nijenhuis, and A. J. Pennings. Design and synthesis of biodegradable poly(ester-urethane) elastomer networks composed of non-toxic building blocks. Die Makromolekulare Chemie, Rapid Commun. 9:589–594 (1988).

    Article  CAS  Google Scholar 

  48. S. L. Elliott, J. D. Fromstein, J. P. Santerre, and K. A. Woodhouse. Identification of biodegradation products formed by L-phenylalanine based segmented polyurethaneureas. J. Biomater. Sci. Polym. Ed. 13:691–711 (2002).

    Article  PubMed  CAS  Google Scholar 

  49. L. Lu, S. J. Peter, M. D. Lyman, H.-L. Lai, S. M. Leite, J. A. Tamada, S. Uyama, J. P. Vacanti, R. Langer, and A. G. Mikos. In vitro and in vivo degradation of porous poly(D-lactic-co-glycolic acid) foams. Biomaterials. 21:1837–1845 (2000).

    Article  PubMed  CAS  Google Scholar 

  50. J. Guan, J. J. Stankus, and W. R. Wagner. Biodegradable elastomeric scaffolds with basic fibroblast growth factor release. J. Control. Release. 120:70–78 (2007).

    Article  PubMed  CAS  Google Scholar 

  51. J.-Y. Zhang, B. A. Doll, E. J. Beckman, and J. O. Hollinger. A biodegradable polyurethane-ascorbic acid scaffold for bone tissue engineering. J. Biomed. Materi. Res. A. 67:389–400 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was funded by the United States Army Institute for Surgical Research (DOD-W81XWH-06–1–0654), the Orthopaedic Trauma Research Program (DOD-W81XWH-07–1–0211), Vanderbilt Skin Diseases Research Core Center (NIH-AR41943), and the Department of Veterans Affairs. The authors acknowledge Jayasri DasGupta and R. Michael Slowey for their assistance with the in vivo studies.

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, Vanderbilt University, Nashville, Tennessee, USA

    Andrea E. Hafeman, Bing Li, Katarzyna Zienkiewicz & Scott A. Guelcher

  2. Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Toshitaka Yoshii

  3. Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Jeffrey M. Davidson

  4. Research Service, VA Tennessee Valley Healthcare System, Nashville, Tennessee, USA

    Jeffrey M. Davidson

Authors
  1. Andrea E. Hafeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshitaka Yoshii
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katarzyna Zienkiewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeffrey M. Davidson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Scott A. Guelcher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott A. Guelcher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hafeman, A.E., Li, B., Yoshii, T. et al. Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration. Pharm Res 25, 2387–2399 (2008). https://doi.org/10.1007/s11095-008-9618-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-008-9618-z

Key Words

Search

Navigation