A growth-accommodating implant for paediatric applications

Abstract

Medical implants of fixed size cannot accommodate normal tissue growth in children and often require eventual replacement or—in some cases—removal, leading to repeated interventions, increased complication rates and worse outcomes. Implants that can correct anatomical deformities and accommodate tissue growth remain an unmet need. Here, we report the design and use of a growth-accommodating device for paediatric applications that consists of a biodegradable core and a tubular braided sleeve, with inversely related sleeve length and diameter. The biodegradable core constrains the diameter of the sleeve, and gradual core degradation following implantation enables sleeve and overall device elongation to accommodate tissue growth. By means of mathematical modelling and ex vivo experiments using harvested swine hearts, we demonstrate the predictability and tunability of the behaviour of the device for disease- and patient-specific needs. We also used the rat tibia and the piglet heart valve as two models of tissue growth to demonstrate that polymer degradation enables device expansion and growth accommodation in vivo.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Growth-accommodating device concept—accelerated degradation model of biaxially braided sleeve and biodegradable core.
Fig. 2: Biaxially braided sleeve, inner polymer and overall device characterization.
Fig. 3: Growing rat musculoskeletal model demonstrating growth restriction with a fixed-size implant and growth accommodation with an autonomously elongating implant.
Fig. 4: Growing piglet heart valve proof-of-concept—exploring the use of a growth-accommodating annuloplasty device in a dynamic cardiovascular environment.

References

  1. 1.

    HCUP Kids’ Inpatient Database. Healthcare Cost and Utilization Project (Agency for Healthcare Research and Quality, 2012); https://hcupnet.ahrq.gov

  2. 2.

    Lam, S., Kuether, J., Fong, A. & Reid, R. Cranioplasty for large-sized calvarial defects in the pediatric population: a review. Craniomaxillofac. Trauma Reconstr. 8, 159–170 (2015).

    Article  PubMed  Google Scholar 

  3. 3.

    Kaza, E. et al. Changes in left atrioventricular valve geometry after surgical repair of complete atrioventricular canal. J. Thorac. Cardiovasc. Surg. 143, 1117–1124 (2012).

    Article  PubMed  Google Scholar 

  4. 4.

    Honjo, O., Mertens, L. & Van Arsdell, G. S. Atrioventricular valve repair in patients with single-ventricle physiology: mechanisms, techniques of repair, and clinical outcomes. Semin. Thorac. Cardiovasc. Surg. Pediatr. Card. Surg. Annu. 14, 75–84 (2011).

    Article  PubMed  Google Scholar 

  5. 5.

    Chavaud, S. et al. Reconstructive surgery in congenital mitral valve insufficiency (Carpentier’s techniques): long-term results. J. Thorac. Cardiovasc. Surg. 115, 84–93 (1998).

    Article  Google Scholar 

  6. 6.

    Dearani, J. A. et al. Anatomic repair of Ebstein’s malformation: lessons learned with Cone reconstruction. Ann. Thorac. Surg. 95, 220–228 (2013).

    Article  PubMed  Google Scholar 

  7. 7.

    Doty, D. B. & Doty, J. R. Cardiac Surgery: Operative Technique (Elsevier, Philadelphia, PA, 2012).

  8. 8.

    Parolari, A., Barili, F., Pilozzi, A. & Pacini, D. Ring or suture annuloplasty for tricuspid regurgitation? A meta-analysis review. Ann. Thorac. Surg. 98, 2255–2263 (2014).

    Article  PubMed  Google Scholar 

  9. 9.

    Tang, G. H. et al. Tricuspid valve repair with an annuloplasty ring results in improved long-term outcomes. Circulation 114, 1577–1581 (2006).

    Article  Google Scholar 

  10. 10.

    Choi, J. B., Kim, K. H., Kim, M. H. & Kim, W. H. Mitral valve re-repair in an adolescent patient with prosthetic ring endocarditis: posterior leaflet augmentation and posterior strip annuloplasty. J. Card. Surg. 27, 560–562 (2012).

    Article  PubMed  Google Scholar 

  11. 11.

    Jonas, R. A. Comprehensive Surgical Management of Congenital Heart Disease (CRC Press, New York, NY, 2014).

  12. 12.

    Kalangos, A. et al. Annuloplasty for valve repair with a new biodegradable ring: an experimental study. J. Heart Valve Dis. 15, 783–790 (2006).

    PubMed  Google Scholar 

  13. 13.

    Bautista-Hernandez, V. et al. Atrioventricular valve annular remodeling with a bioabsorbable ring in young children. J. Am. Coll. Cardiol. 60, 2255–2260 (2012).

    Article  Google Scholar 

  14. 14.

    Lee, T. M. et al. Risk factor analysis for second-stage palliation of single ventricle anatomy. Ann. Thorac. Surg. 93, 614–619 (2012).

    Article  PubMed  Google Scholar 

  15. 15.

    Friend, L. & Widmann, R. F. Advances in management of limb length discrepancy and lower limb deformity. Curr. Opin. Pediatr. 20, 46–51 (2008).

    Article  PubMed  Google Scholar 

  16. 16.

    Goldman, V. & Green, D. W. Advances in growth plate modulation for lower extremity malalignment (knock knees and bow legs). Curr. Opin. Pediatr. 22, 47–53 (2010).

    Article  PubMed  Google Scholar 

  17. 17.

    Boero, S., Michelis, M. B. & Riganti, S. Use of the eight-plate for angular correction of knee deformities due to idiopathic and pathologic physis: initiating treatment according to etiology. J. Child. Orthop. 5, 209–216 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Stevens, P. M. Guided growth: 1933 to the present. Strat. Traum. Limb Recon. 1, 29–35 (2006).

    Article  Google Scholar 

  19. 19.

    Burnette, J. B. et al. Incidence of inpatient surgeries in children and young adults with childhood orthopedic diagnoses. J. Pediatr. Orthop. 24, 738–741 (2004).

    Article  PubMed  Google Scholar 

  20. 20.

    Sturm, P. F., Anadio, J. M. & Dede, O. Recent advances in the management of early onset scoliosis. Orhop. Clin. N. Am. 45, 501–514 (2014).

    Article  Google Scholar 

  21. 21.

    Betz, R. R. et al. Vertebral body stapling: a fusionless treatment option for a growing child with moderate idiopathic scoliosis. Spine 35, 169–176 (2010).

    Article  PubMed  Google Scholar 

  22. 22.

    Samdani, A. F. et al. Anterior vertebral body tethering for immature adolescent scoliosis: on year results on the first 32 patients. Eur. Spine J. 24, 1533–1539 (2015).

    Article  PubMed  Google Scholar 

  23. 23.

    Daerden, F. & Lefeber, D. Pneumatic artificial muscles: actuators for robotics and automation. Eur. J. Mech. Environ. Eng. 47, 11–21 (2002).

    Google Scholar 

  24. 24.

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

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Doumit, M., Fahim, A. & Munro, M. Analytical modeling and experimental validation of the braided pneumatic muscle. IEEE Trans. Robot. 25, 1282–1291 (2009).

    Article  Google Scholar 

  26. 26.

    Wang, Y., Kim, Y. M. & Langer, R. Technical note: in vivo degradation characteristics of poly(glycerol sebacate). J. Biomed. Mater. Res. 66A, 192–197 (2003).

    CAS  Article  Google Scholar 

  27. 27.

    Pomerantseva, I. et al. Degradation behavior of poly(glycerol sebacate). J. Biomed. Mater. Res. 91A, 1038–1047 (2009).

    CAS  Article  Google Scholar 

  28. 28.

    Stokes, I. A. F., Aronsson, D. D., Dimock, A. N., Cortright, V. & Beck, S. Endochondral growth in growth plates of three species at two anatomical locations modulated by mechanical compression and tension. J. Orthop. Res. 24, 1327–1334 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Sundback, C. A. et al. Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material. Biomaterials 26, 5454–5464 (2005).

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Greenwald, D., Shumway, S., Albear, P. & Gottlieb, L. Mechanical comparison of 10 suture materials before and after in vivo incubation. J. Surg. Res. 56, 372–377 (1995).

    Article  Google Scholar 

  31. 31.

    Bylski-Austrow, D. I., Wall, E. J., Rupert, M. P., Roy, D. R. & Crawford, A. H. Growth plate forces in the adolescent human knee: a radiographic and mechanical study of epiphyseal staples. J. Pediatr. Orthop. 21, 817–823 (2001).

    CAS  PubMed  Google Scholar 

  32. 32.

    Siefert, A. W. et al. In-vivo mitral annuloplasty ring transducer: implications for implantation and annular downsizing. J. Biomech. 46, 2550–2553 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Sun, Z. et al. Glycolic acid modulates the mechanical property and degradation of poly(glycerol, sebacate, glycolic acid). J. Biomed. Mater. Res. A 92A, 332–339 (2010).

    CAS  Article  Google Scholar 

  34. 34.

    Colan, S. D. The why and how of Z scores. J. Am. Soc. Echocardiogr. 25, 1–2 (2013).

    Google Scholar 

  35. 35.

    Dimeglio, A. & Canavese, F. The growing spine: how spinal deformities influence normal spine and thoracic cage growth. Eur. Spine J. 21, 64–70 (2012).

    Article  PubMed  Google Scholar 

  36. 36.

    Wolford, L. M., Movahed, R. & Perez, D. E. A classification system for conditions causing condylar hyperplasia. J. Oral Maxillofac. Surg. 72, 567–595 (2014).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Animal Research Children’s Hospital staff (A. Nedder (head veterinarian) and veterinary technicians) and the Boston Children’s Hospital perfusion team for their overwhelming support and assistance in this project. This work was also supported by the National Institutes of Health (grant GM086433 to J.M.K.) and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education of Korea (2012R1A6A3A03041166) and the Korea Institute for Advancement of Technology (N0002123) to Y.L.

Author information

Affiliations

Authors

Contributions

E.N.F and Y.L. designed and performed the experiments, analysed the data and wrote the manuscript. E.D.O. contributed to the design of the experiments. N.V.V., S.S. and I.F. contributed to the design and performance of the experiments and to the analysis of the data. D.P., P.E.H., H.Y., A.G. and V.A. contributed to the design of the experiments. G.M. contributed to the analysis of the data. P.J.d.N. and J.M.K. contributed to the experimental design and manuscript preparation and supervised the overall project. All authors read and edited the manuscript.

Corresponding authors

Correspondence to Jeffrey M. Karp or Pedro J. del Nido.

Ethics declarations

Competing interests

E.N.F., Y.L., E.D.O., N.V.V., D.P., P.E.H., H.Y., V.A., J.M.K. and P.J.d.N. have a provisional patent application entitled ‘Autonomously growing implantable device’ (USSN 62/295,768).

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

41551_2017_142_MOESM3_ESM.mov

Representative video of a growth-accommodating annuloplasty ring in an ex vivo swine-heart preparation. The video is en face view of the tricuspid valve, with the ring in place. 100× normal speed

Supplementary Information

Supplementary figures, tables and methods.

Life Sciences Reporting Summary

Supplementary Video 1

Representative video of a growth-accommodating annuloplasty ring in an ex vivo swine-heart preparation. The video is en face view of the tricuspid valve, with the ring in place. 100× normal speed

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Feins, E.N., Lee, Y., O’Cearbhaill, E.D. et al. A growth-accommodating implant for paediatric applications. Nat Biomed Eng 1, 818–825 (2017). https://doi.org/10.1038/s41551-017-0142-5

Download citation

Further reading