Skip to main content

Advertisement

Log in

Elastase-Sensitive Elastomeric Scaffolds with Variable Anisotropy for Soft Tissue Engineering

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

Abstract

Purpose

To develop elastase-sensitive polyurethane scaffolds that would be applicable to the engineering of mechanically active soft tissues.

Methods

A polyurethane containing an elastase-sensitive peptide sequence was processed into scaffolds by thermally induced phase separation. Processing conditions were manipulated to alter scaffold properties and anisotropy. The scaffold’s mechanical properties, degradation, and cytocompatibility using muscle-derived stem cells were characterized. Scaffold in vivo degradation was evaluated by subcutaneous implantation.

Results

When heat transfer was multidirectional, scaffolds had randomly oriented pores. Imposition of a heat transfer gradient resulted in oriented pores. Both scaffolds were flexible and relatively strong with mechanical properties dependent upon fabrication conditions such as solvent type, polymer concentration and quenching temperature. Oriented scaffolds exhibited anisotropic mechanical properties with greater tensile strength in the orientation direction. These scaffolds also supported muscle-derived stem cell growth more effectively than random scaffolds. The scaffolds expressed over 40% weight loss after 56 days in elastase containing buffer. Elastase-sensitive scaffolds were complete degraded after 8 weeks subcutaneous implantation in rats, markedly faster than similar polyurethanes that did not contain the peptide sequence.

Conclusion

The elastase-sensitive polyurethane scaffolds showed promise for application in soft tissue engineering where controlling scaffold mechanical properties and pore architecture are desirable.

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

Access this article

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

Instant access to the full article PDF.

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

References

  1. L. E. Niklason, J. Gao, W. M. Abbott, K. K. Hirschi, S. Houser, R. Marini, and R. Langer. Functional arteries grown in vitro. Science. 284:489–493 (1999).

    Article  PubMed  CAS  Google Scholar 

  2. S. P. Hoerstrup, G. Zund, R. Sodian, A. M. Schnell, J. Grunenfelder, and M. I. Turina. Tissue engineering of small caliber vascular grafts. Eur. J. Cardiothorac. Surg. 20:164–169 (2001).

    Article  PubMed  CAS  Google Scholar 

  3. A. Tiwari, H. J. Salacinski, G. Punshon, G. Hamilton, and A. M. Seifalian. Development of a hybrid cardiovascular graft using a tissue engineering approach. FASEB J. 16:791–796 (2002).

    Article  PubMed  CAS  Google Scholar 

  4. F. Opitz, K. Schenke-Layland, W. Richter, D. P. Martin, I. Degenkolbe, T. Wahlers, and U. A. Stock. Tissue engineering of ovine aortic blood vessel substitutes using applied shear stress and enzymatically derived vascular smooth muscle cells. Ann. Biomed. Eng. 32:212–222 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. J. Guan, and W. R. Wagner. Synthesis, characterization and cytocompatibility of polyurethaneurea elastomers with designed elastase sensitivity. Biomacromolecules. 6:2833–2842 (2005).

    Article  PubMed  CAS  Google Scholar 

  6. 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 

  7. 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 

  8. J. Guan, M. S. Sacks, E. J. Beckman, and W. R. Wagner. Synthesis, characterization, and cytocompatibility of elastomeric, biodegradable poly(ester-urethane)ureas based on poly(caprolactone) and putrescine. J. Biomed. Mater. Res. 61:493–503 (2002).

    Article  PubMed  CAS  Google Scholar 

  9. J. D. Fromstein, and K. A. Woodhouse. Elastomeric biodegradable polyurethane blends for soft tissue application. J. Biomater. Sci. Polymer. Ed. 13:391–406 (2002).

    Article  CAS  Google Scholar 

  10. L. Tatai, T. G. Moore, R. Adhikari, F. Malherbe, R. Jayasekara, I. Griffiths, and P. A. Gunatillake. Thermoplastic biodegradable polyurethanes: the effect of chain extender structure on properties and in-vitro degradation. Biomaterials. 28:5407–5417 (2007).

    Article  PubMed  CAS  Google Scholar 

  11. K. D. Kavlock, T. W. Pechar, J. O. Hollinger, S. A. Guelcher, and A. S. Goldstein. Synthesis and characterization of segmented poly(esterurethane urea) elastomers for bone tissue engineering. Acta Biomater. 3:475–484 (2007).

    Article  PubMed  CAS  Google Scholar 

  12. Q. Z. Chen, A. Bismarck, U. Hansen, S. Junaid, M. Q. Tran, S. E. Harding, N. N. Ali, and A. R. Boccaccini. Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue. Biomaterials. 29:47–57 (2008).

    Article  PubMed  Google Scholar 

  13. Y. Wang, G. Ameer, B. Sheppard, and R. Langer. A tough biodegradable elastomer. Nat. Biotechnol. 20:602–606 (2002).

    Article  PubMed  CAS  Google Scholar 

  14. J. Yang, A. Webb, and G. A. Ameer. Novel citric acid-based biodegradable elastomers for tissue engineering. Adv. Mater. 16:511–516 (2004).

    Article  CAS  Google Scholar 

  15. R. Murugan, and S. Ramakrishna. Design strategies of tissue engineering scaffolds with controlled fiber orientation. Tissue Eng. 13:1845–1866 (2007).

    Article  PubMed  CAS  Google Scholar 

  16. Q. P. Pham, U. Sharma, and A. G. Mikos. Electrospinning of polymeric nanofibers for tissue engineering applications: a review. Tissue Eng. 12:1197–1211 (2006).

    Article  PubMed  CAS  Google Scholar 

  17. T. Courtney, M. S. Sacks, J. J. Stankus, J. Guan, and W. R. Wagner. Design and analysis of tissue engineering scaffolds that mimic soft tissue mechanical anisotropy. Biomaterials. 27:3631–3638 (2006).

    PubMed  CAS  Google Scholar 

  18. K. Fujimoto, M. Minato, S. Miyamoto, T. Kaneko, H. Kikuchi, K. Sakai, M. Okada, and Y. Ikada. Porous polyurethane tubes as vascular graft. J. Appl. Biomater. 4:347–354 (1993).

    Article  PubMed  CAS  Google Scholar 

  19. R. P. Kowligi, W. W. von Maltzahn, and R. C. Eberhart. Fabrication and characterization of small-diameter vascular prostheses. J. Biomed. Mater. Res. 22:245–256 (1988).

    Article  PubMed  CAS  Google Scholar 

  20. K. Doi, Y. Nakayama, and T. Matsuda. Novel compliant and tissue permeable microporous polyurethane vascular prosthesis fabricated using an excimer laser ablation technique. J. Biomed. Mater. Res. 31:27–33 (1996).

    Article  PubMed  CAS  Google Scholar 

  21. S. Q. Liu, and M. Kodama. Porous polyurethane vascular prostheses with variable compliances. J. Biomed. Mater. Res. 26:1489–1494 (1992).

    Article  PubMed  CAS  Google Scholar 

  22. Y. S. Nam, and T. G. Park. Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation. J. Biomed. Mater. Res. 47:8–17 (1999).

    Article  PubMed  CAS  Google Scholar 

  23. R. Y. Zhang, and P. X. Ma. Poly(a-hydroxyl acids)/hydroxyapatite porous composites for bone-tissue engineering. I. Preparation and morphology. J. Biomed. Mater. Res. 44:446–455 (1999).

    Article  PubMed  CAS  Google Scholar 

  24. P. X. Ma, and R. Y. Zhang. Microtubular architecture of biodegradable polymer scaffolds. J. Biomed. Mater. Res. 56:469–477 (2001).

    Article  PubMed  CAS  Google Scholar 

  25. F. Yang, X. Qu, W. J. Cui, J. Z. Bei, F. Y. Yu, S. B. Lu, and S. G. Wang. Manufacturing and morphology structure of polylactide-type microtubules orientation-structured scaffolds. Biomaterials. 27:4923–4933 (2006).

    Article  PubMed  CAS  Google Scholar 

  26. A. S. Rowlands, S. A. Lim, D. Martin, and J. J. Cooper-White. Polyurethane/poly(lactic-co-glycolic) acid composite scaffolds fabricated by thermally induced phase separation. Biomaterials. 28:2109–2121 (2007).

    Article  PubMed  CAS  Google Scholar 

  27. 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 

  28. J. Guan, J. J. Stankus, and W. R. Wagner. Development of composite porous scaffolds based on collagen and biodegradable poly(ester urethane)urea. Cell Transplant. 15:S17–S27 (2006).

    Article  PubMed  Google Scholar 

  29. Y. Y. Hsu, J. D. Gresser, D. J. Trantolo, C. M. Lyons, P. R. Gangadharam, and D. L. Wise. Effect of polymer foam morphology and density on kinetics of in vitro controlled release of isoniazid from compressed foam matrices. J. Biomed. Mater. Res. 35:107–116 (1997).

    Article  PubMed  CAS  Google Scholar 

  30. Z. Qu-Petersen, B. Deasy, R. Jankowski, M. Ikezawa, J. Cummins, R. Pruchnic, J. Mytinger, B. Cao, C. Gates, A. Wernig, and J. Huard. Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. J. Cell Biol. 157:851–864 (2002).

    Article  PubMed  CAS  Google Scholar 

  31. H. Oshima, T. R. Payne, K. L. Urish, T. Sakai, Y. Ling, B. Gharaibeh, K. Tobita, B. B. Keller, J. H. Cummins, and J. Huard. Differential myocardial infarct repair with muscle stem cells compared to myoblasts. Molec. Ther. 12:1130–1141 (2005).

    Article  CAS  Google Scholar 

  32. R. V. Ulijn. Enzyme-responsive materials: a new class of smart biomaterials. J. Mater. Chem. 16:2217–2225 (2006).

    Article  CAS  Google Scholar 

  33. J. L. West, and J. A. Hubbell. Polymeric biomaterials with degradation sites for proteases involved in cell migration. Macromolecules. 32:241–244 (1999).

    Article  CAS  Google Scholar 

  34. B. K. Mann, A. S. Gobin, A. T. Tsai, R. H. Schmedlen, and J. L. West. Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. Biomaterials. 22:3045–3051 (2001).

    Article  PubMed  CAS  Google Scholar 

  35. S. Kim, E. H Chung, M. Gilbert, and K. E. Healy. Synthetic MMP-13 degradable ECMs based on poly(N-isopropylacrylamide-co-acrylic acid) semi-interpenetrating polymer networks. I. Degradation and cell migration. J. Biomed. Mater. Res. A. 75:73–88 (2005).

    PubMed  Google Scholar 

  36. S. G. Lévesque, and M. S. Shoichet. Synthesis of enzyme-degradable, peptide-cross-linked dextran hydrogels. Bioconjug. Chem. 18:874–885 (2007).

    Article  PubMed  Google Scholar 

  37. G. P. Raeber, M. P. Lutolf, and J. A. Hubbell. Mechanisms of 3-D migration and matrix remodeling of fibroblasts within artificial ECMs. Acta Biomater. 3:615–629 (2007).

    Article  PubMed  CAS  Google Scholar 

  38. A. S. Gobin, and J. L. West. Cell migration through defined, synthetic extracellular matrix analogs. FASEB J. 16:751–753 (2002).

    PubMed  CAS  Google Scholar 

  39. T. P. Kraehenbuehl, P. Zammaretti, A. J. Van der Vlies, R. G. Schoenmakers, M. P. Lutolf, M. E. Jaconi, and J. A. Hubbell. Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: systematic modulation of a synthetic cell-responsive PEG–hydrogel. Biomaterials. 29:2757–2766 (2008).

    Article  PubMed  CAS  Google Scholar 

  40. C. J. Spaans, J. H. de Groot, F. G. Dekens, and A. J. Pennings. High molecular weight polyurethanes and a polyurethane urea based on 1,4-butanediisocyanate. Polym. Bull. 41:131–138 (1998).

    Article  CAS  Google Scholar 

  41. J. Boublik, H. Park, M. Radisic, E. Tognana, F. Chen, M. Pei, G. Vunjak-Novakovic, and L. E. Freed. Mechanical properties and remodeling of hybrid cardiac constructs made from heart cells, fibrin, and biodegradable, elastomeric knitted fabric. Tissue Eng. 11:1122–1132 (2005).

    Article  PubMed  CAS  Google Scholar 

  42. K. L. Fujimoto, J. Guan, H. Oshima, T. Sakai, and W. R. Wagner. In vivo evaluation of a porous, elastic, biodegradable patch for reconstructive cardiac procedures. Ann. Thorac. Surg. 83:648–654 (2007).

    Article  PubMed  Google Scholar 

  43. K. L. Fujimoto, K. Tobita, W. D. Merryman, J. Guan, N. Momoi, D. B. Stolz, M. S. Sacks, B. B. Keller, and W. R. Wagner. An elastic, biodegradable cardiac patch induces contractile smooth muscle and improves cardiac remodeling and function in subacute myocardial infarction. J. Am. Coll. Cardiol. 49:2292–2300 (2007).

    Article  PubMed  CAS  Google Scholar 

  44. G. A. Skarja, and K. A. Woodhouse. Synthesis and characterization of degradable polyurethane elastomers containing and amino acid-based chain extender. J. Biomater. Sci. Polym. Ed. 9:271–295 (1998).

    Article  PubMed  CAS  Google Scholar 

  45. G. A. Skarja, and K.A. Woodhouse. In vitro degradation and erosion of degradable, segmented polyurethanes containing an amino acid-based chain extender. J. Biomater. Sci. Polym. Ed. 12:851–873 (2001).

    Article  PubMed  CAS  Google Scholar 

  46. J. D. Fromstein, P. W. Zandstra, C. Alperin, D. Rockwood, J. F. Rabolt, and K.A. Woodhouse. Seeding bioreactor-produced embryonic stem cell-derived cardiomyocytes on different porous, degradable, polyurethane scaffolds reveals the effect of scaffold architecture on cell morphology. Tissue Eng. Part A. 14:369–378 (2008).

    Article  PubMed  CAS  Google Scholar 

  47. D. L. Dinnes, J. P. Santerre, and R. S. Labow. Influence of biodegradable and non-biodegradable material surfaces on the differentiation of human monocyte-derived macrophages. Differentiation. 76:232–244 (2008).

    Article  PubMed  CAS  Google Scholar 

  48. L. K. Carr, D. Steele, S. Steele, D. Wagner, R. Pruchnic, R. Jankowski, J. Erickson, J. Huard, and M. B. Chancellor. 1-year follow-up of autologous muscle-derived stem cell injection pilot study to treat stress urinary incontinence. Int. Urogynecol. J. 19:881–883 (2008).

    Article  Google Scholar 

  49. T. R. Payne, H. Oshima, M. Okada, N. Momoi, K. Tobita, B. B. Keller, H. Peng, and J. Huard. A relationship between vascular endothelial growth factor, angiogenesis, and cardiac repair after muscle stem cell transplantation into ischemic hearts. J. Am. Coll. Cardiol. 50:1685–1687 (2007).

    Article  Google Scholar 

Download references

Acknowledgement

This work was supported by the National Institutes of Health (grant no. HL069368). We are grateful to the laboratory of Dr. Johnny Huard at the University of Pittsburgh for their provision of mouse muscle derived stem cells.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William R. Wagner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guan, J., Fujimoto, K.L. & Wagner, W.R. Elastase-Sensitive Elastomeric Scaffolds with Variable Anisotropy for Soft Tissue Engineering. Pharm Res 25, 2400–2412 (2008). https://doi.org/10.1007/s11095-008-9628-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-008-9628-x

KEY WORDS

Navigation