Rare Metals

, Volume 34, Issue 3, pp 143–155 | Cite as

Regenerative engineering and bionic limbs

  • Roshan James
  • Cato T. LaurencinEmail author


Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counseling. There is no prosthesis that allows the amputees near normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities, and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material, and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feedback to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits, and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past 30 years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feedback will be the important goals in regenerative engineering over the next two decades.


Bionic Electrical stimulation Regenerative engineering Muscle Nerve Prosthetic 



Authors gratefully acknowledge funding from the Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences. Authors also acknowledge the funding from National Science Foundation Award (Nos. IIP-1311907, IIP-1355327 and EFRI-1332329). Dr. Laurencin was the recipient of the Presidential Faculty Fellowship Award from President William Clinton and the Presidential Award for Excellence in Science, Mathematics, and Engineering Mentorship from President Barack Obama. Dr. Laurencin is the recipient of the NIH Director’s Pioneer Award (No. 1DP1AR068147-01).

Conflict of interest

C.T. Laurencin discloses a financial interest (stock and consulting agreement) in Soft Tissue Regeneration Incorporated, Natural Polymer Devices Incorporated and Novartis International AG. The author (C.T. Laurencin) also discloses receiving royalties from Globus Medical Inc. R.J. declares no conflict of interest.


  1. [1]
    Pidcoke HF, Aden JK, Mora AG, Borgman MA, Spinella PC, Dubick MA, Blackbourne LH, Cap AP. Ten-year analysis of transfusion in operation iraqi freedom and operation enduring freedom: increased plasma and platelet use correlates with improved survival. J Trauma Acute Care Surg. 2012;73(S5):S445.CrossRefGoogle Scholar
  2. [2]
    Paulus N, Jacobs M, Greiner A. Primary and secondary amputation in critical limb ischemia patients: different aspects. Acta Chir Belg. 2012;112(4):251.Google Scholar
  3. [3]
    Laurencin CT, Khan Y. Regenerative engineering. Sci Transl Med. 2012;4(160):160ed9.Google Scholar
  4. [4]
    Krueger CA, Wenke JC, Ficke JR. Ten years at war: comprehensive analysis of amputation trends. J Trauma Acute Care Surg. 2012;73(6 Suppl 5):S438.CrossRefGoogle Scholar
  5. [5]
    Jones WS, Patel MR, Dai D, Subherwal S, Stafford J, Calhoun S, Peterson ED. Temporal trends and geographic variation of lower-extremity amputation in patients with peripheral artery disease: results from U.S. Medicare 2000–2008. J Am Coll Cardiol. 2012;60(21):2230.CrossRefGoogle Scholar
  6. [6]
    Hammarlund CS, Carlstrom M, Melchior R, Persson BM. Prevalence of back pain, its effect on functional ability and health-related quality of life in lower limb amputees secondary to trauma or tumour: a comparison across three levels of amputation. Prosthet Orthot Int. 2011;35(1):97.CrossRefGoogle Scholar
  7. [7]
    Miyajima S, Shirai A, Yamamoto S, Okada N, Matsushita T. Risk factors for major limb amputations in diabetic foot gangrene patients. Diabetes Res Clin Pract. 2006;71(3):272.CrossRefGoogle Scholar
  8. [8]
    Zlotolow DA, Kozin SH. Advances in upper extremity prosthetics. Hand Clin. 2012;28(4):587.CrossRefGoogle Scholar
  9. [9]
    Yang WM, Shalumon KT, Tang X, Ramos DM, Laurencin CT, Kumbar SG. Optimization of Bioactive Polymer–Ceramic Nanocomposite Scaffolds for Bone Regenerative Engineering, in American Association for Dental Research/International Association for Dental Research. Charlotte, NC: International Association for Dental Research; 2014. 593.Google Scholar
  10. [10]
    James R, Daley GQ, Laurencin CT. Regenerative engineering: materials, mimicry, and manipulations to promote cell and tissue growth. Sharp PA, Langer R editors. National Academy of Engineering - The Bridge: The Convergence of Engineering and the Life Sciences. 2013; 43(3):8.Google Scholar
  11. [11]
    Peach MS, Roshan J, Udaya ST, Meng D, Nicole LM, Harry RA, Cato TL, Sangamesh GK. Polyphosphazene functionalized polyester fiber matrices for tendon tissue engineering: in vitro evaluation with human mesenchymal stem cells. Biomed Mater. 2012;7(4):045016.CrossRefGoogle Scholar
  12. [12]
    Kumbar SG, Toti US, Deng M, James R, Laurencin CT, Aravamudhan A, Harmon M, Ramos DM. Novel mechanically competent polysaccharide scaffolds for bone tissue engineering. Biomed Mater. 2011;6(6):065005.CrossRefGoogle Scholar
  13. [13]
    James R, Toti US, Laurencin CT, Kumbar SG. Electrospun nanofibrous scaffolds for engineering soft connective tissues. Methods Mol Biol (Clifton, N.J.). 2011;726:243.CrossRefGoogle Scholar
  14. [14]
    James R, Kumbar SG, Laurencin CT, Balian G, Chhabra AB. Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems. Biomed Mater. 2011;6(2):025011.CrossRefGoogle Scholar
  15. [15]
    Jiang T, Khan Y, Nair LS, Abdel-Fattah WI, Laurencin CT. Functionalization of chitosan/poly(lactic acid–glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering. J Biomed Mater Res A. 2010;93(3):1193.Google Scholar
  16. [16]
    Deng M, Nair LS, Nukavarapu SP, Kumbar SG, Jiang T, Weikel AL, Krogman NR, Allcock HR, Laurencin CT. In situ porous structures: a unique polymer erosion mechanism in biodegradable dipeptide-based polyphosphazene and polyester blends producing matrices for regenerative engineering. Adv Funct Mater. 2010;20(17):2794.CrossRefGoogle Scholar
  17. [17]
    Kumbar SG, James R, Nukavarapu SP, Laurencin CT. Electrospun nanofiber scaffolds: engineering soft tissues. Biomed Mater (Bristol, England). 2008;3(3):034002.CrossRefGoogle Scholar
  18. [18]
    Laurencin CT, Khan Y. Regenerative engineering. Sci Transl Med. 2012;4(160):160ed9.Google Scholar
  19. [19]
    Lake C, Dodson R. Progressive upper limb prosthetics. Phys Med Rehabil Clin N Am. 2006;17(1):49.CrossRefGoogle Scholar
  20. [20]
    González-Fernández M. Development of upper limb prostheses: current progress and areas for growth. Arch Phys Med Rehabil. 2014;95(6):1013.CrossRefGoogle Scholar
  21. [21]
    Mourino V, Cattalini JP, Boccaccini AR. Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments. J R Soc Interface. 2012;9(68):401.CrossRefGoogle Scholar
  22. [22]
    Gerard C, Bordeleau LJ, Barralet J, Doillon CJ. The stimulation of angiogenesis and collagen deposition by copper. Biomaterials. 2010;31(5):824.CrossRefGoogle Scholar
  23. [23]
    Taylor A. Therapeutic uses of trace elements. Clin Endocrinol Metab. 1985;14(3):703.CrossRefGoogle Scholar
  24. [24]
    Schultz AE, Kuiken TA. Neural interfaces for control of upper limb prostheses: the state of the art and future possibilities. PM&R. 2011;3(1):55.CrossRefGoogle Scholar
  25. [25]
    Alley R, Sears H. Powered Upper Limb Prosthetics in Adults, in Powered Upper Limb Prostheses. New York: Springer; 2004. 117.Google Scholar
  26. [26]
    Jones L, Davidson J. Save that arm: a study of problems in the remaining arm of unilateral upper limb amputees. Prosthet Orthot Int. 1999;23(1):55.Google Scholar
  27. [27]
    Spiegel SR. Adult Myoelectric Upper-Limb Prosthetic Training, in Comprehensive Management of the Upper-Limb Amputee. New York: Springer; 1989. 60.Google Scholar
  28. [28]
    Biddiss EA, Chau TT. Upper limb prosthesis use and abandonment: a survey of the last 25 years. Prosthet Orthot Int. 2007;31(3):236.CrossRefGoogle Scholar
  29. [29]
    Biddiss E, Chau T. Upper-limb prosthetics: critical factors in device abandonment. Am J Phys Med Rehabil. 2007;86(12):977.CrossRefGoogle Scholar
  30. [30]
    Agnew SP, Ko J, De La Garza M, Kuiken T, Dumanian G. Limb transplantation and targeted reinnervation: a practical comparison. J Reconstr Microsurg. 2012;28(1):63.CrossRefGoogle Scholar
  31. [31]
    Kuiken TA, Li G, Lock BA, Lipschutz RD, Miller LA, Stubblefield KA, Englehart KB. Targeted muscle reinnervation for real-time myoelectric control of multifunction artificial arms. JAMA. 2009;301(6):619.CrossRefGoogle Scholar
  32. [32]
    Kuiken T. Targeted reinnervation for improved prosthetic function. Phys Med Rehabil Clin N Am. 2006;17(1):1.CrossRefGoogle Scholar
  33. [33]
    Kaufman CL, Breidenbach W. World experience after more than a decade of clinical hand transplantation: update from the Louisville hand transplant program. Hand Clin. 2011;27(4):417.CrossRefGoogle Scholar
  34. [34]
    Petruzzo P, Lanzetta M, Dubernard JM, Landin L, Cavadas P, Margreiter R, Schneeberger S, Breidenbach W, Kaufman C, Jablecki J, Schuind F, Dumontier C. The international registry on hand and composite tissue transplantation. Transplantation. 2010;90(12):1590.CrossRefGoogle Scholar
  35. [35]
    Chung KC, Oda T, Saddawi-Konefka D, Shauver MJ. An economic analysis of hand transplantation in the United States. Plast Reconstr Surg. 2010;125(2):589.CrossRefGoogle Scholar
  36. [36]
    Jones NF, Schneeberger S. Arm transplantation: prospects and visions. Transplant Proc. 2009;41(2):476.CrossRefGoogle Scholar
  37. [37]
    Petruzzo P, Lanzetta M, Dubernard JM, Margreiter R, Schuind F, Breidenbach W, Nolli R, Schneeberger S, van Holder C, Kaufman C, Jablecki J, Landin L, Cavadas P. The international registry on hand and composite tissue transplantation. Transplantation. 2008;86(4):487.CrossRefGoogle Scholar
  38. [38]
    Agnew SP, Ko J, De La Garza M, Kuiken T, Dumanian G. Limb transplantation and targeted reinnervation: a practical comparison. J Reconstr Microsurg. 2012;28(01):63.CrossRefGoogle Scholar
  39. [39]
    Kuiken TA, Dumanian GA, Lipschutz RD, Miller LA, Stubblefield KA. The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthet Orthot Int. 2004;28(3):245.Google Scholar
  40. [40]
    Kuiken T. Targeted reinnervation for improved prosthetic function. Phys Med Rehabil Clin N Am. 2006;17(1):1.CrossRefGoogle Scholar
  41. [41]
    Gutmann E. The reinnervation of muscle by sensory nerve fibres. J Anat. 1945;79:1.Google Scholar
  42. [42]
    Kuiken TA, Marasco PD, Lock BA, Harden RN, Dewald JP. Redirection of cutaneous sensation from the hand to the chest skin of human amputees with targeted reinnervation. Proc Natl Acad Sci USA. 2007;104(50):20061.CrossRefGoogle Scholar
  43. [43]
    Sensinger JW, Schultz AE, Kuiken TA. Examination of force discrimination in human upper limb amputees with reinnervated limb sensation following peripheral nerve transfer. IEEE Trans Neural Syst Rehabil Eng. 2009;17(5):438.CrossRefGoogle Scholar
  44. [44]
    Dhillon GS, Lawrence SM, Hutchinson DT, Horch KW. Residual function in peripheral nerve stumps of amputees: implications for neural control of artificial limbs. J Hand Surg Am. 2004;29(4):605.CrossRefGoogle Scholar
  45. [45]
    Hudson TW, Evans GR, Schmidt CE. Engineering strategies for peripheral nerve repair. Orthop Clin N Am. 2000;31(3):485.CrossRefGoogle Scholar
  46. [46]
    Edell DJ. A peripheral nerve information transducer for amputees: long-term multichannel recordings from rabbit peripheral nerves. IEEE Trans Biomed Eng. 1986;33(2):203.CrossRefGoogle Scholar
  47. [47]
    Hoffer JA, Loeb GE. Implantable electrical and mechanical interfaces with nerve and muscle. Ann Biomed Eng. 1980;8(4–6):351.CrossRefGoogle Scholar
  48. [48]
    De Luca CJ. Control of upper-limb prostheses: a case for neuroelectric control. J Med Eng Technol. 1978;2(2):57.CrossRefGoogle Scholar
  49. [49]
    Jia X, Koenig MA, Zhang X, Zhang J, Chen T, Chen Z. Residual motor signal in long-term human severed peripheral nerves and feasibility of neural signal-controlled artificial limb. J Hand Surg Am. 2007;32(5):657.CrossRefGoogle Scholar
  50. [50]
    Dhillon GS, Horch KW. Direct neural sensory feedback and control of a prosthetic arm. IEEE Trans Neural Syst Rehabil Eng. 2005;13(4):468.CrossRefGoogle Scholar
  51. [51]
    Margalit E, Maia M, Weiland JD, Greenberg RJ, Fujii GY, Torres G, Piyathaisere DV, O’Hearn TM, Liu W, Lazzi G. Retinal prosthesis for the blind. Surv Ophthalmol. 2002;47(4):335.CrossRefGoogle Scholar
  52. [52]
    Miranda PC, Sampaio AL, Lopes RA, Ramos Venosa A, de Oliveira CA. Hearing preservation in cochlear implant surgery. Int. J Otolaryngol. 2014;2014:468515.Google Scholar
  53. [53]
    Navarro X, Krueger TB, Lago N, Micera S, Stieglitz T, Dario P. A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems. J Peripher Nerv Syst. 2005;10(3):229.CrossRefGoogle Scholar
  54. [54]
    Leventhal DK, Durand DM. Chronic measurement of the stimulation selectivity of the flat interface nerve electrode. IEEE Trans Biomed Eng. 2004;51(9):1649.CrossRefGoogle Scholar
  55. [55]
    Foldes EL, Ackermann DM, Bhadra N, Kilgore KL, Bhadra N. Design, fabrication and evaluation of a conforming circumpolar peripheral nerve cuff electrode for acute experimental use. J Neurosci Methods. 2011;196(1):31.CrossRefGoogle Scholar
  56. [56]
    Burridge J, Haugland M, Larsen B, Pickering RM, Svaneborg N, Iversen HK, Christensen PB, Haase J, Brennum J, Sinkjaer T. Phase II trial to evaluate the ActiGait implanted drop-foot stimulator in established hemiplegia. J Rehabil Med. 2007;39(3):212.CrossRefGoogle Scholar
  57. [57]
    Ward MP, Rajdev P, Ellison C, Irazoqui PP. Toward a comparison of microelectrodes for acute and chronic recordings. Brain Res. 2009;1282:183.CrossRefGoogle Scholar
  58. [58]
    Branner A, Stein RB, Fernandez E, Aoyagi Y, Normann RA. Long-term stimulation and recording with a penetrating microelectrode array in cat sciatic nerve. IEEE Trans Biomed Eng. 2004;51(1):146.CrossRefGoogle Scholar
  59. [59]
    Lago N, Ceballos D, Rodríguez FJ, Stieglitz T, Navarro X. Long term assessment of axonal regeneration through polyimide regenerative electrodes to interface the peripheral nerve. Biomaterials. 2005;26(14):2021.CrossRefGoogle Scholar
  60. [60]
    Badia J, Boretius T, Andreu D, Azevedo-Coste C, Stieglitz T, Navarro X. Comparative analysis of transverse intrafascicular multichannel, longitudinal intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles. J Neural Eng. 2011;8(3):036023.CrossRefGoogle Scholar
  61. [61]
    Mathews KS, Wark HA, Normann RA. Assessment of rat sciatic nerve function following acute implantation of high density Utah slanted electrode array (25 electrodes/mm(2)) based on neural recordings and evoked muscle activity. Muscle Nerve. 2014;50(3):417.CrossRefGoogle Scholar
  62. [62]
    Christensen MB, Pearce SM, Ledbetter NM, Warren DJ, Clark GA, Tresco PA. The foreign body response to the Utah Slant Electrode Array in the cat sciatic nerve. Acta Biomater. 2014;10(11):4650.CrossRefGoogle Scholar
  63. [63]
    Egan J, Baker J, House P, Greger B. Detection and classification of multiple finger movements using a chronically implanted Utah Electrode Array. Conf Proc IEEE Eng Med Biol Soc. 2011;2011:7320.Google Scholar
  64. [64]
    Smith SL, Judy JW, Otis TS. An ultra small array of electrodes for stimulating multiple inputs into a single neuron. J Neurosci Methods. 2004;133(1–2):109.Google Scholar
  65. [65]
    Cottman E. Nanotextured Surfaces: New Generation Bioelectronic Interfaces for Nanomedicine (NNIN REU). Richmond, VA: Virginia Commonwealth University-Electrical Engineering Research Accomplishments; 2009. 6.Google Scholar
  66. [66]
    Moxon KA, Kalkhoran NM, Markert M, Sambito MA, McKenzie JL, Webster JT. Nanostructured surface modification of ceramic-based microelectrodes to enhance biocompatibility for a direct brain–machine interface. IEEE Trans Biomed Eng. 2004;51(6):881.CrossRefGoogle Scholar
  67. [67]
    Sharp PA, Langer R. Promoting convergence in biomedical science. Science. 2011;333(6042):527.CrossRefGoogle Scholar
  68. [68]
    Kim YH, Lee C, Ahn KM, Lee M, Kim YJ. Robust and real-time monitoring of nerve regeneration using implantable flexible microelectrode array. Biosens Bioelectron. 2009;24(7):1883.CrossRefGoogle Scholar
  69. [69]
    Garde K, Keefer E, Botterman B, Galvan P, Romero MI. Early interfaced neural activity from chronic amputated nerves. Front Neuroeng. 2009;2:5.CrossRefGoogle Scholar
  70. [70]
    Cipriani C, Antfolk C, Balkenius C, Rosen B, Lundborg G, Carrozza MC, Sebelius F. A novel concept for a prosthetic hand with a bidirectional interface: a feasibility study. IEEE Trans Biomed Eng. 2009;56(11):2739.CrossRefGoogle Scholar
  71. [71]
    Lebedev MA, Nicolelis MA. Brain–machine interfaces: past, present and future. Trends Neurosci. 2006;29(9):536.CrossRefGoogle Scholar
  72. [72]
    Chatterjee A, Aggarwal V, Ramos A, Acharya S, Thakor NV. A brain–computer interface with vibrotactile biofeedback for haptic information. J Neuroeng Rehabil. 2007;4:40.CrossRefGoogle Scholar
  73. [73]
    Peach MS, Kumbar SG, James R, Toti US, Balasubramaniam D, Deng M, Ulery B, Mazzocca AD, McCarthy MB, Morozowich NL, Allcock HR, Laurencin CT. Design and optimization of polyphosphazene functionalized fiber matrices for soft tissue regeneration. J Biomed Nanotechnol. 2012;8(1):107.CrossRefGoogle Scholar
  74. [74]
    James R. Novel tissue engineering strategies for tendon repair and regeneration, in biomedical engineering. Charlottesville: University of Virginia; 2012. 1.Google Scholar
  75. [75]
    James R, Deng M, Laurencin C, Kumbar S. Nanocomposites and bone regeneration. Front Mater Sci. 2011;5(4):342.CrossRefGoogle Scholar
  76. [76]
    Kumbar SG, Nukavarapu SP, James R, Nair LS, Laurencin CT. Electrospun poly(lactic acid-co-glycolic acid) scaffolds for skin tissue engineering. Biomaterials. 2008;29(30):4100.Google Scholar
  77. [77]
    James R, Kesturu G, Balian G, Chhabra AB. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am. 2008;33A(1):102.CrossRefGoogle Scholar
  78. [78]
    Ferrandez JM, Lorente V, de Santos D, Cuadra JM, de la Paz F, Alvarez JR, Fernandez E. Human neuroblastoma cultures for biorobotics. Conf Proc IEEE Eng Med Biol Soc. 2011;2011:6672.Google Scholar
  79. [79]
    Hampton S, King L. Healing an intractable wound using bio-electrical stimulation therapy. Br J Nurs. 2005;14(15S):S30.CrossRefGoogle Scholar
  80. [80]
    Williams HB. The value of continuous electrical muscle stimulation using a completely implantable system in the preservation of muscle function following motor nerve injury and repair: an experimental study. Microsurgery. 1996;17(11):589.CrossRefGoogle Scholar
  81. [81]
    Mercola JM, Kirsch DL. The basis for microcurrent electrical therapy in conventional medical practice. J Adv Med. 1995;8(2):107.Google Scholar
  82. [82]
    Stanish WD, Rubinovich M, Kozey J, MacGillvary G. The use of electricity in ligament and tendon repair. Physician Sportsmed. 1985;13(8):108.Google Scholar
  83. [83]
    Stanish WD, Lai A. New concepts of rehabilitation following anterior cruciate reconstruction. Clin Sports Med. 1993;12(1):25.Google Scholar
  84. [84]
    Hudlicka O, Milkiewicz M, Cotter MA, Brown MD. Hypoxia and expression of VEGF-A protein in relation to capillary growth in electrically stimulated rat and rabbit skeletal muscles. Exp Physiol. 2002;87(3):373.CrossRefGoogle Scholar
  85. [85]
    Gavin TP, Spector DA, Wagner H, Breen EC, Wagner PD. Nitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise. J Appl Physiol. 2000;88(4):1192.Google Scholar
  86. [86]
    Kanno S, Oda N, Abe M, Saito S, Hori K, Handa Y, Tabayashi K, Sato Y. Establishment of a simple and practical procedure applicable to therapeutic angiogenesis. Circulation. 1999;99(20):2682.CrossRefGoogle Scholar
  87. [87]
    Hudlicka O, Brown MD, Egginton S, Dawson JM. Effect of long-term electrical stimulation on vascular supply and fatigue in chronically ischemic muscles. J Appl Physiol. 1994;77(3):1317.Google Scholar
  88. [88]
    Kim D-H, Viventi J, Amsden JJ, Xiao J, Vigeland L, Kim Y-S, Blanco JA, Panilaitis B, Frechette ES, Contreras D, Kaplan DL, Omenetto FG, Huang Y, Hwang K-C, Zakin MR, Litt B, Rogers JA. Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. Nat Mater. 2010;9(6):511.CrossRefGoogle Scholar
  89. [89]
    Vepari C, Kaplan DL. Silk as a biomaterial. Prog Polym Sci. 2007;32(8):991.CrossRefGoogle Scholar
  90. [90]
    Tao H, Kaplan DL, Omenetto FG. Silk materials—a road to sustainable high technology. Adv Mater. 2012;24(21):2824.CrossRefGoogle Scholar
  91. [91]
    Kim DH, Kim YS, Amsden J, Panilaitis B, Kaplan DL, Omenetto FG, Zakin MR, Rogers JA. Silicon electronics on silk as a path to bioresorbable, implantable devices. Appl Phys Lett. 2009;95(13):133701.CrossRefGoogle Scholar
  92. [92]
    Tsioris K, Tao H, Liu M, Hopwood JA, Kaplan DL, Averitt RD, Omenetto FG. Rapid transfer-based micropatterning and dry etching of silk microstructures. Adv Mater. 2011;23(17):2015.CrossRefGoogle Scholar
  93. [93]
    Tao H, Siebert SM, Brenckle MA, Averitt RD, Cronin-Golomb M, Kaplan DL, Omenetto FG. Gold nanoparticle-doped biocompatible silk films as a path to implantable thermo-electrically wireless powering devices. Appl Phys Lett. 2010;97(12):123702.CrossRefGoogle Scholar
  94. [94]
    Dickinson MH, Farley CT, Full RJ, Koehl MA, Kram R, Lehman S. How animals move: an integrative view. Science. 2000;288(5463):100.CrossRefGoogle Scholar
  95. [95]
    Feinberg AW, Feigel A, Shevkoplyas SS, Sheehy S, Whitesides GM, Parker KK. Muscular thin films for building actuators and powering devices. Science. 2007;317(5843):1366.CrossRefGoogle Scholar
  96. [96]
    Sakar MS, Neal D, Boudou T, Borochin MA, Li Y, Weiss R, Kamm RD, Chen CS, Asada HH. Formation and optogenetic control of engineered 3D skeletal muscle bioactuators. Lab Chip. 2012;12(23):4976.CrossRefGoogle Scholar
  97. [97]
    Selimovic S, Dokmeci MR, Khademhosseini A. Research highlights. Lab Chip. 2012;12(24):5127.CrossRefGoogle Scholar
  98. [98]
    Byl NN, McKenzie A, Wong T, West J, Hunt TK. Incisional wound healing: a controlled study of low and high dose ultrasound. J Orthop Sports Phys Ther. 1993;18(5):619.CrossRefGoogle Scholar
  99. [99]
    Byl NN, McKenzie AL, West JM, Whitney J, Hunt T, Scheuenstuhl H. Low-dose ultrasound effects on wound healing: a controlled study with Yucatan pigs. Arch Phys Med Rehabil. 1992;73(7):656.Google Scholar
  100. [100]
    Crisci AR, Ferreira AL. Low-intensity pulsed ultrasound accelerates the regeneration of the sciatic nerve after neurotomy in rats. Ultrasound Med Biol. 2002;28(10):1335.CrossRefGoogle Scholar
  101. [101]
    Chang CJ. SH Hsu, The effects of low-intensity ultrasound on peripheral nerve regeneration in poly(dl-lactic acid-co-glycolic acid) conduits seeded with Schwann cells. Ultrasound Med Biol. 2004;30(8):1079.Google Scholar
  102. [102]
    Schofer MD, Block JE, Aigner J, Schmelz A. Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial. BMC Musculoskelet Disord. 2010;11:229.CrossRefGoogle Scholar
  103. [103]
    Patino O, Grana D, Bolgiani A, Prezzavento G, Mino J, Merlo A, Benaim F. Pulsed electromagnetic fields in experimental cutaneous wound healing in rats. J Burn Care Res. 1996;17(6):528.CrossRefGoogle Scholar
  104. [104]
    Shi HF, Xiong J, Chen YX, Wang JF, Qiu XS, Wang YH, Qiu Y. Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: a prospective randomized controlled study. BMC Musculoskelet Disord. 2013;14:35.CrossRefGoogle Scholar

Copyright information

© The Nonferrous Metals Society of China and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Institute for Regenerative EngineeringUniversity of Connecticut Health CenterFarmingtonUSA
  2. 2.Raymond and Beverly Sackler Center for Biological, Physical and Engineering SciencesUniversity of Connecticut Health CenterFarmingtonUSA
  3. 3.Department of Orthopaedic SurgeryUniversity of Connecticut Health CenterFarmingtonUSA
  4. 4.Connecticut Institute for Clinical and Translational ScienceFarmingtonUSA
  5. 5.Department of Chemical, Materials and Biomolecular EngineeringUniversity of ConnecticutStorrsUSA

Personalised recommendations