Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The current state of scaffolds for musculoskeletal regenerative applications

Nature Reviews Rheumatology volume 11, pages 213–222 (2015)Cite this article

Subjects

Key Points

  • Scaffolds are an essential component of the tissue engineering triad concept and should provide form, fixation and function, as well as drive tissue formation

  • Natural scaffold materials are highly biocompatible, biodegradable and have multiple attachment sites for cells

  • Synthetic scaffolds can be manufactured to have highly predictive properties

  • Scaffolds for the regeneration of articular cartilage, tendon and meniscus have been investigated in many clinical trials, but there is no consensus on the best material or technique

  • Clinical study of scaffold-based bone and skeletal muscle tissue engineering has been limited by the need for vascularization and the complex physiological and biomechanical requirements of these tissues

  • The other two elements of the tissue engineering triad, cells and growth factors, have a role in the clinical application of scaffold-based musculoskeletal tissue engineering

Abstract

Musculoskeletal disease and injury are highly prevalent conditions that lead to many surgical procedures. Autologous tissue transfer, allograft transplantation and nontissue prosthetics are currently used for the surgical treatment of critical-sized defects. However, the field of tissue engineering is actively investigating tissue-replacement solutions, many of which involve 3D scaffolds. Scaffolds must provide a balance of shape, biomechanical function and biocompatibility in order to achieve tissue replacement success. Different tissues can have different requirements for success, which has led to the development of various materials with unique characteristics. Articular cartilage scaffolds have the most robust clinical experience, with many scaffolds, mostly constructed of natural materials, showing promise, but levels of success vary. Tendon scaffolds also have proven clinical applications, with human-dermis-derived scaffolds showing the most potential. Synthetic and naturally derived meniscus scaffolds have been investigated in few clinical studies, but the results are encouraging. Bone scaffolds are limited to amorphous pastes and putties, owing to difficulties achieving adequate vascularization and biomechanical optimization. The complex physiological function and vascular demands of skeletal muscle have limited the widespread clinical use of scaffolds for engineering this tissue. Continued progress in preclinical study, not only of scaffolds, but also of other facets of tissue engineering, should enable the successful translation of musculoskeletal tissue engineering solutions to the clinic.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The role of scaffolds in tissue engineering strategies.
Figure 2: Use of scaffolds in musculoskeletal repair.
Figure 3: Matrix-assisted chondrocyte implantation in cartilage repair.
Figure 4: Scaffolds used as adjuncts in cartilage repair.
Figure 5: Scaffolds for tendon repair.
Figure 6: Example of fixed-shape bone scaffold.
Figure 7: Scaffolds for meniscus repair.

Similar content being viewed by others

References

  1. United States Bone and Joint Initiative. The Burden of Musculoskeletal Diseases in the United States, 2nd edn (American Academy of Orthopaedic Surgeons, Rosemont, 2011).

  2. Gamie, Z. et al. Stem cells combined with bone graft substitutes in skeletal tissue engineering. Expert Opin. Biol. Ther. 12, 713–729 (2012).

    Article  CAS  PubMed  Google Scholar 

  3. Li, M. T., Willett, N. J., Uhrig, B. A., Guldberg, R. E. & Warren, G. L. Functional analysis of limb recovery following autograft treatment of volumetric muscle loss in the quadriceps femoris. J. Biomech. 47, 2013–2021 (2014).

    Article  PubMed  Google Scholar 

  4. Mariscalco, M. W. et al. Autograft versus nonirradiated allograft tissue for anterior cruciate ligament reconstruction: a systematic review. Am. J. Sports Med. 42, 492–499 (2014).

    Article  PubMed  Google Scholar 

  5. Shrivats, A. R., Mcdermott, M. C. & Hollinger, J. O. Bone tissue engineering: state of the union. Drug Discov. Today 19, 781–786 (2014).

    Article  CAS  PubMed  Google Scholar 

  6. Zmistowski, B., Karam, J. A., Durinka, J. B., Casper, D. S. & Parvizi, J. Periprosthetic joint infection increases the risk of one-year mortality. J. Bone Joint Surg. Am. 95, 2177–2184 (2013).

    Article  PubMed  Google Scholar 

  7. Langer, R. & Vacanti, J. P. Tissue engineering. Science 260, 920–926 (1993).

    Article  CAS  PubMed  Google Scholar 

  8. Murphy, C. M., O'Brien, F. J., Little, D. G. & Schindeler, A. Cell–scaffold interactions in the bone tissue engineering triad. Eur. Cell. Mater. 26, 120–132 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. Hollister, S. J. & Murphy, W. L. Scaffold translation: barriers between concept and clinic. Tissue Eng. Part B Rev. 17, 459–474 (2011).

    Article  PubMed Central  PubMed  Google Scholar 

  10. Scotti, C., Hirschmann, M. T., Antinolfi, P., Martin, I. & Peretti, G. M. Meniscus repair and regeneration: review on current methods and research potential. Eur. Cell. Mater. 26, 150–170 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. Behrens, P., Bitter, T., Kurz, B. & Russlies, M. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)—5-year follow-up. Knee 13, 194–202 (2006).

    Article  PubMed  Google Scholar 

  12. Ronga, M., Grassi, F. A., Manelli, A. & Bulgheroni, P. Tissue engineering techniques for the treatment of a complex knee injury. Arthroscopy 22, 576.e1–576.e3 (2006).

    Article  Google Scholar 

  13. Gigante, A. et al. Distal realignment and patellar autologous chondrocyte implantation: mid-term results in a selected population. Knee Surg. Sports Traumatol. Arthrosc. 17, 2–10 (2009).

    Article  PubMed  Google Scholar 

  14. Basad, E., Ishaque, B., Bachmann, G., Stürz, H. & Steinmeyer, J. Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: a 2-year randomised study. Knee Surg. Sports Traumatol. Arthrosc. 18, 519–527 (2010).

    Article  PubMed  Google Scholar 

  15. Macmull, S. et al. The role of autologous chondrocyte implantation in the treatment of symptomatic chondromalacia patellae. Int. Orthop. 36, 1371–1377 (2012).

    Article  PubMed Central  PubMed  Google Scholar 

  16. Bauer, S. et al. Knee joint preservation with combined neutralising high tibial osteotomy (HTO) and matrix-induced autologous chondrocyte implantation (MACI) in younger patients with medial knee osteoarthritis: a case series with prospective clinical and MRI follow-up over 5 years. Knee 19, 431–439 (2012).

    Article  CAS  PubMed  Google Scholar 

  17. Ventura, A. et al. Repair of osteochondral lesions in the knee by chondrocyte implantation using the MACI® technique. Knee Surg. Sports Traumatol. Arthrosc. 20, 121–126 (2012).

    Article  PubMed  Google Scholar 

  18. Gille, J. et al. Outcome of autologous matrix induced chondrogenesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch. Orthop. Trauma Surg. 133, 87–93 (2013).

    Article  CAS  PubMed  Google Scholar 

  19. Pascarella, A. et al. Treatment of articular cartilage lesions of the knee joint using a modified AMIC technique. Knee Surg. Sports Traumatol. Arthrosc. 18, 509–513 (2010).

    Article  PubMed  Google Scholar 

  20. Dhollander, A. A. et al. Autologous matrix-induced chondrogenesis combined with platelet-rich plasma gel: technical description and a five pilot patients report. Knee Surg. Sports Traumatol. Arthrosc. 19, 536–542 (2011).

    Article  CAS  PubMed  Google Scholar 

  21. Schiavone Panni, A., Cerciello, S. & Vasso, M. The manangement of knee cartilage defects with modified amic technique: preliminary results. Int. J. Immunopathol. Pharmacol. 24 (1 Suppl. 2), 149–152 (2011).

    Article  CAS  PubMed  Google Scholar 

  22. Kusano, T. et al. Treatment of isolated chondral and osteochondral defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Knee Surg. Sports Traumatol. Arthrosc. 20, 2109–2115 (2012).

    Article  PubMed  Google Scholar 

  23. Nehrer, S. et al. Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair. Eur. J. Radiol. 57, 3–8 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Ferruzzi, A. et al. Autologous chondrocyte implantation in the knee joint: open compared with arthroscopic technique. Comparison at a minimum follow-up of five years. J. Bone Joint Surg. Am. 90 (Suppl. 4), 90–101 (2008).

    Article  PubMed  Google Scholar 

  25. Kon, E. et al. Arthroscopic second-generation autologous chondrocyte implantation compared with microfracture for chondral lesions of the knee: prospective nonrandomized study at 5 years. Am. J. Sports Med. 37, 33–41 (2009).

    Article  PubMed  Google Scholar 

  26. Gobbi, A. et al. Patellofemoral full-thickness chondral defects treated with second-generation autologous chondrocyte implantation: results at 5 years' follow-up. Am. J. Sports Med. 37, 1083–1092 (2009).

    Article  PubMed  Google Scholar 

  27. Clar, H. et al. Matrix-assisted autologous chondrocyte implantation into a 14cm2 cartilage defect, caused by steroid-induced osteonecrosis. Knee 17, 255–257 (2010).

    Article  CAS  PubMed  Google Scholar 

  28. Kon, E. et al. Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up. Eur. J. Radiol. 79, 382–388 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Kon, E. et al. Articular cartilage treatment in high-level male soccer players: a prospective comparative study of arthroscopic second-generation autologous chondrocyte implantation versus microfracture. Am. J. Sports Med. 39, 2549–2557 (2011).

    Article  PubMed  Google Scholar 

  30. Kon, E. V. et al. Second-generation autologous chondrocyte implantation: results in patients older than 40 years. Am. J. Sports Med. 39, 1668–1675 (2011).

    Article  PubMed  Google Scholar 

  31. Filardo G. et al. Arthroscopic second generation autologous chondrocytes implantation associated with bone grafting for the treatment of knee osteochondritis dissecans: results at 6 years. Knee 19, 658–663 (2012).

    Article  PubMed  Google Scholar 

  32. Brix, M. O. et al. Treatment of full-thickness chondral defects with hyalograft C in the knee: long-term results. Am. J. Sports Med. 42, 1426–1432 (2014).

    Article  PubMed  Google Scholar 

  33. Nehrer, S., Dorotka, R., Domayer, S., Stelzeneder, D. & Kotz, R. Treatment of full-thickness chondral defects with hyalograft C in the knee: a prospective clinical case series with 2 to 7 years' follow-up. Am. J. Sports Med. 37 (Suppl. 1), 81S–87S (2009).

    Article  PubMed  Google Scholar 

  34. Filardo, G., Kon, E., Di Martino, A., Iacono, F. & Marcacci, M. Arthroscopic second-generation autologous chondrocyte implantation: a prospective 7-year follow-up study. Am. J. Sports Med. 39, 2153–2160 (2011).

    Article  PubMed  Google Scholar 

  35. Filardo, G. et al. Second-generation arthroscopic autologous chondrocyte implantation for the treatment of degenerative cartilage lesions. Knee Surg. Sports Traumatol. Arthrosc. 20, 1704–1713 (2012).

    Article  PubMed  Google Scholar 

  36. De Windt, T. S., Concaro, S., Lindahl, A., Saris, D. B. & Brittberg, M. Strategies for patient profiling in articular cartilage repair of the knee: a prospective cohort of patients treated by one experienced cartilage surgeon. Knee Surg. Sports Traumatol. Arthrosc. 20, 2225–2232 (2012).

    Article  PubMed Central  PubMed  Google Scholar 

  37. Chevrier, A., Hoemann, C. D., Sun, J. & Buschmann, M. D. Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularization and subchondral bone remodeling in drilled cartilage defects. Osteoarthritis Cartilage 15, 316–327 (2007).

    Article  CAS  PubMed  Google Scholar 

  38. Stanish, W. D. et al. Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. J. Bone Joint Surg. Am. 95, 1640–1650 (2013).

    Article  PubMed  Google Scholar 

  39. Steinwachs, M. R., Waibl, B. & Mumme, M. Arthroscopic treatment of cartilage lesions with microfracture and BST-CarGel. Arthrosc. Tech. 3, e399–e402 (2014).

    Article  PubMed Central  PubMed  Google Scholar 

  40. Ossendorf, C. et al. Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: 2-year clinical results. Arthritis Res. Ther. 9, R41 (2007).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Kreuz, P. C., Müller, S., Ossendorf, C., Kaps, C. & Erggelet, C. Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res. Ther. 11, R33 (2009).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Erggelet, C. et al. Autologous chondrocyte implantation versus ACI using 3D-bioresorbable graft for the treatment of large full-thickness cartilage lesions of the knee. Arch. Orthop. Trauma Surg. 130, 957–964 (2010).

    Article  PubMed  Google Scholar 

  43. Kreuz, P. C. et al. Repair of focal cartilage defects with scaffold-assisted autologous chondrocyte grafts: clinical and biomechanical results 48 months after transplantation. Am. J. Sports Med. 39, 1697–1705 (2011).

    Article  PubMed  Google Scholar 

  44. Zeifang, F. et al. Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: a randomized clinical trial. Am. J. Sports Med. 38, 924–933 (2010).

    Article  PubMed  Google Scholar 

  45. Nukavarapu, S. P. & Dorcemus, D. L. Osteochondral tissue engineering: current strategies and challenges. Biotechnol. Adv. 31, 706–721 (2013).

    Article  CAS  PubMed  Google Scholar 

  46. US National Institutes of Health. ClinicalTrials.gov [online], (2014).

  47. Filardo, G. et al. Osteochondral scaffold reconstruction for complex knee lesions: a comparative evaluation. Knee 20, 570–576 (2013).

    Article  CAS  PubMed  Google Scholar 

  48. Steele, J. A. et al. Combinatorial scaffold morphologies for zonal articular cartilage engineering. Acta Biomater. 10, 2065–2075 (2014).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Joshi, N., Reverte-vinaixa, M., Díaz-Ferreiro, E. W. & Domínguez-Oronoz, R. Synthetic resorbable scaffolds for the treatment of isolated patellofemoral cartilage defects in young patients: magnetic resonance imaging and clinical evaluation. Am. J. Sports Med. 40, 1289–1295 (2012).

    Article  PubMed  Google Scholar 

  50. Gott, M. et al. Tendon phenotype should dictate tissue engineering modality in tendon repair: a review. Discov. Med. 12, 75–84 (2011).

    PubMed  Google Scholar 

  51. Ricchetti, E. T., Aurora, A., Iannotti, J. P. & Derwin, K. A. Scaffold devices for rotator cuff repair. J. Shoulder Elbow Surg. 21, 251–265 (2012).

    Article  PubMed  Google Scholar 

  52. Barber, F. A., Burns, J. P., Deutsch, A., Labbé, M. R. & Litchfield, R. B. A prospective, randomized evaluation of acellular human dermal matrix augmentation for arthroscopic rotator cuff repair. Arthroscopy 28, 8–15 (2012).

    Article  PubMed  Google Scholar 

  53. Dopirak, R., Bond, J. L. & Snyder, S. J. Arthroscopic total rotator cuff replacement with an acellular human dermal allograft matrix. Int. J. Shoulder Surg. 1, 7–15 (2007).

    Article  Google Scholar 

  54. Burkhead, W. Z., Schiffern, S. C. & Krishnan, S. G. Use of GraftJacket as an augmentation for massive rotator cuff tears. Semin. Arthroplasty 18, 11–18 (2007).

    Article  Google Scholar 

  55. Bond, J. L., Dopirak, R. M., Higgins, J., Burns, J. & Snyder, S. J. Arthroscopic replacement of massive, irreparable rotator cuff tears using a GraftJacket allograft: technique and preliminary results. Arthroscopy 24, 403.e1–403.e8 (2008).

    Article  Google Scholar 

  56. Wong, I., Burns, J. & Snyder, S. Arthroscopic GraftJacket repair of rotator cuff tears. J. Shoulder Elbow Surg. 19 (2 Suppl.), 104–109 (2010).

    Article  PubMed  Google Scholar 

  57. Metcalf, M. H., Savoie, F. H. III & Kellum, B. Surgical technique for xeno-graft (SIS) augmentation of rotator-cuff repairs. Oper. Tech. Orthop. 12, 204–208 (2002).

    Article  Google Scholar 

  58. Sclamberg, S. G., Tibone, J. E., Itamura, J. M. & Kasraeian, S. Six-month magnetic resonance imaging follow-up of large and massive rotator cuff repairs reinforced with porcine small intestinal submucosa. J. Shoulder Elbow Surg. 13, 538–541 (2004).

    Article  PubMed  Google Scholar 

  59. Iannotti, J. P. et al. Porcine small intestine submucosa augmentation of surgical repair of chronic two-tendon rotator cuff tears. A randomized, controlled trial. J. Bone Joint Surg. Am. 88, 1238–1244 (2006).

    Article  PubMed  Google Scholar 

  60. Malcarney, H. L., Bonar, F. & Murrell, G. A. Early inflammatory reaction after rotator cuff repair with a porcine small intestine submucosal implant: a report of 4 cases. Am. J. Sports Med. 33, 907–911 (2005).

    Article  PubMed  Google Scholar 

  61. Walton, J. R., Bowman, N. K., Khatib, Y., Linklater, J. & Murrell, G. A. Restore orthobiologic implant: not recommended for augmentation of rotator cuff repairs. J. Bone Joint Surg. Am. 89, 786–791 (2007).

    PubMed  Google Scholar 

  62. Daly, K. A. et al. Effect of the αGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. Tissue Eng. Part A 15, 3877–3888 (2009).

    Article  CAS  PubMed  Google Scholar 

  63. Xu, H. et al. A porcine-derived acellular dermal scaffold that supports soft tissue regeneration: removal of terminal galactose-α-(1,3)-galactose and retention of matrix structure. Tissue Eng. Part A 15, 1807–1819 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Proctor, C. S. Long-term successful arthroscopic repair of large and massive rotator cuff tears with a functional and degradable reinforcement device. J. Shoulder Elbow Surg. 23, 1508–1513 (2014).

    Article  PubMed  Google Scholar 

  65. Encalada-Diaz, I. et al. Rotator cuff repair augmentation using a novel polycarbonate polyurethane patch: preliminary results at 12 months' follow-up. J. Shoulder Elbow Surg. 20, 788–794 (2011).

    Article  PubMed  Google Scholar 

  66. Zhang, X., Bogdanowicz, D., Erisken, C., Lee, N. M. & Lu, H. H. Biomimetic scaffold design for functional and integrative tendon repair. J. Shoulder Elbow Surg. 21, 266–277 (2012).

    Article  PubMed Central  PubMed  Google Scholar 

  67. Lu, H. H. & Thomopoulos, S. Functional attachment of soft tissues to bone: development, healing, and tissue engineering. Annu. Rev. Biomed. Eng. 15, 201–226 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Moffat, K. L. et al. In vitro and in vivo evaluation of a bi-phasic nanofiber scaffold for integrative rotator cuff repair [poster #482]. Transactions of Orthopeadic Research Society 2011 Annual Meeting [online], (2011).

    Google Scholar 

  69. Nguyen, L. H. et al. Vascularized bone tissue engineering: approaches for potential improvement. Tissue Eng. Part B Rev. 18, 363–382 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Oryan, A., Alidadi, S., Moshiri, A. & Maffulli, N. Bone regenerative medicine: classic options, novel strategies, and future directions. J. Orthop. Surg. Res. 9, 18 (2014).

    Article  PubMed Central  PubMed  Google Scholar 

  71. Smucker, J. D., Petersen, E. B. & Fredericks, D. C. Assessment of Mastergraft putty as a graft extender in a rabbit posterolateral fusion model. Spine (Phila. PA 1976) 37, 1017–1021 (2012).

    Article  Google Scholar 

  72. Miller, C. P. et al. The efficacies of 2 ceramic bone graft extenders for promoting spinal fusion in a rabbit bone paucity model. Spine (Phila. PA 1976) 37, 642–647 (2012).

    Article  Google Scholar 

  73. Kapur, R. A. et al. Clinical outcomes and fusion success associated with the use of BoneSave in spinal surgery. Arch. Orthop. Trauma Surg. 130, 641–647 (2010).

    Article  PubMed  Google Scholar 

  74. Blom, A. W. et al. Impaction bone grafting of the acetabulum at hip revision using a mix of bone chips and a biphasic porous ceramic bone graft substitute. Acta Orthop. 80, 150–154 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  75. Whitehouse, M. R., Dacombe, P. J., Webb, J. C. & Blom, A. W. Impaction grafting of the acetabulum with ceramic bone graft substitute mixed with femoral head allograft: high survivorship in 43 patients with a median follow-up of 7 years: a follow-up report. Acta Orthop. 84, 365–370 (2013).

    Article  PubMed Central  PubMed  Google Scholar 

  76. Burkus, J. K., Gornet, M. F., Dickman, C. A. & Zdeblick, T. A. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J. Spinal Disord. Tech. 15, 337–349 (2002).

    Article  PubMed  Google Scholar 

  77. Burkus, J. K., Transfeldt, E. E., Kitchel, S. H., Watkins, R. G. & Balderston, R. A. Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2. Spine (Phila. PA 1976) 27, 2396–2408 (2002).

    Article  Google Scholar 

  78. Govender, S. et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J. Bone Joint Surg. Am. 84, 2123–2134 (2002).

    Article  PubMed  Google Scholar 

  79. Hashmi, S., Noureldin, M. & Khan, S. N. Lessons from the infuse trials: do we need a classification of bias in scientific publications and editorials? Curr. Rev. Musculoskelet. Med. 7, 193–199 (2014).

    Article  PubMed Central  PubMed  Google Scholar 

  80. Moreau, J. L., Weir, M. D. & Xu, H. H. Self-setting collagen-calcium phosphate bone cement: mechanical and cellular properties. J. Biomed. Mater. Res. A 91, 605–613 (2009).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. van staden, A. D. & Dicks, L. M. Calcium orthophosphate-based bone cements (CPCs): applications, antibiotic release and alternatives to antibiotics. J. Appl. Biomater. Funct. Mater. 10, 2–11 (2012).

    PubMed  Google Scholar 

  82. Hollister, S. J. & Murphy, W. L. Scaffold translation: barriers between concept and clinic. Tissue Eng. Part B Rev. 17, 459–474 (2011).

    Article  PubMed Central  PubMed  Google Scholar 

  83. Quarto R et al. Repair of large bone defects with the use of autologous bone marrow stromal cells. N. Engl. J. Med. 344, 385–386 (2001).

    Article  CAS  PubMed  Google Scholar 

  84. Marcacci, M. et al. Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. Tissue Eng. 13, 947–955 (2007).

    Article  CAS  PubMed  Google Scholar 

  85. Zhang, Z. Y. et al. Neo-vascularization and bone formation mediated by fetal mesenchymal stem cell tissue-engineered bone grafts in critical-size femoral defects. Biomaterials 31, 608–620 (2010).

    Article  CAS  PubMed  Google Scholar 

  86. Wang, L. et al. Osteogenesis and angiogenesis of tissue-engineered bone constructed by prevascularized β-tricalcium phosphate scaffold and mesenchymal stem cells. Biomaterials 31, 9452–9461 (2010).

    Article  CAS  PubMed  Google Scholar 

  87. Zhao, M. et al. Repair of bone defect with vascularized tissue engineered bone graft seeded with mesenchymal stem cells in rabbits. Microsurgery 31, 130–137 (2011).

    Article  CAS  PubMed  Google Scholar 

  88. Choi, H. J. et al. Establishment of efficacy and safety assessment of human adipose tissue-derived mesenchymal stem cells (hATMSCs) in a nude rat femoral segmental defect model. J. Korean Med. Sci. 26, 482–491 (2011).

    Article  PubMed Central  PubMed  Google Scholar 

  89. Diab, T. et al. A silk hydrogel-based delivery system of bone morphogenetic protein for the treatment of large bone defects. J. Mech. Behav. Biomed. Mater. 11, 123–131 (2012).

    Article  CAS  PubMed  Google Scholar 

  90. Fan, Z. X. et al. Placenta- versus bone-marrow-derived mesenchymal cells for the repair of segmental bone defects in a rabbit model. FEBS J. 279, 2455–2465 (2012).

    Article  CAS  PubMed  Google Scholar 

  91. Hou, J. et al. Segmental bone regeneration using rhBMP-2-loaded collagen/chitosan microspheres composite scaffold in a rabbit model. Biomed. Mater. 7, 035002 (2012).

    Article  CAS  PubMed  Google Scholar 

  92. Cao, L. et al. Experimental repair of segmental bone defects in rabbits by angiopoietin-1 gene transfected MSCs seeded on porous β-TCP scaffolds. J. Biomed. Mater. Res. Part B Appl. Biomater. 100, 1229–1236 (2012).

    Article  CAS  Google Scholar 

  93. Bagher Z., Rajaei, F. & Shokrgozar, M. Comparative study of bone repair using porous hydroxyapatite/β-tricalcium phosphate and xenograft scaffold in rabbits with tibia defect. Iran Biomed. J. 16, 18–24 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  94. De Guzman, R, C, et al. Bone regeneration with BMP-2 delivered from keratose scaffolds. Biomaterials 34, 1644–1656 (2013).

    Article  CAS  PubMed  Google Scholar 

  95. Rongen, J. J., van Tienen, T. G., van Bochove, B., Grijpma, D. W. & Buma, P. Biomaterials in search of a meniscus substitute. Biomaterials 35, 3527–3540 (2014).

    Article  CAS  PubMed  Google Scholar 

  96. Stone, K. R., Steadman, J. R., Rodkey, W. G. & Li, S. T. Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data. J. Bone Joint Surg. Am. 79, 1770–1777 (1997).

    Article  CAS  PubMed  Google Scholar 

  97. Steadman, J. R. & Rodkey, W. G. Tissue-engineered collagen meniscus implants: 5- to 6-year feasibility study results. Arthroscopy 21, 515–525 (2005).

    Article  PubMed  Google Scholar 

  98. Rodkey, W. G. et al. Comparison of the collagen meniscus implant with partial meniscectomy. A prospective randomized trial. J. Bone Joint Surg. Am. 90, 1413–1426 (2008).

    Article  PubMed  Google Scholar 

  99. Bulgheroni, P. et al. Follow-up of collagen meniscus implant patients: clinical, radiological, and magnetic resonance imaging results at 5 years. Knee 17, 224–229 (2010).

    Article  PubMed  Google Scholar 

  100. Zaffagnini, S. et al. Prospective long-term outcomes of the medial collagen meniscus implant versus partial medial meniscectomy: a minimum 10-year follow-up study. Am. J. Sports Med. 39, 977–985 (2011).

    Article  PubMed  Google Scholar 

  101. Linke, R. D., Ulmer, M. &, Imhoff, A. B. Replacement of the meniscus with a collagen implant (CMI) [English, German]. Oper. Orthop. Traumatol. 18, 453–462 (2006).

    Article  PubMed  Google Scholar 

  102. Verdonk, R., Verdonk, P., Huysse, W., Forsyth, R. & Heinrichs, E. L. Tissue ingrowth after implantation of a novel, biodegradable polyurethane scaffold for treatment of partial meniscal lesions. Am. J. Sports Med. 39, 774–782 (2011).

    Article  PubMed  Google Scholar 

  103. Verdonk, P. et al. Successful treatment of painful irreparable partial meniscal defects with a polyurethane scaffold: two-year safety and clinical outcomes. Am. J. Sports Med. 40, 844–853 (2012).

    Article  PubMed  Google Scholar 

  104. Bouyarmane, H. et al. Polyurethane scaffold in lateral meniscus segmental defects: clinical outcomes at 24 months follow-up. Orthop. Traumatol. Surg. Res. 100, 153–157 (2014).

    Article  CAS  PubMed  Google Scholar 

  105. Koning, M., Harmsen, M. C., Van luyn, M. J. & Werker, P. M. Current opportunities and challenges in skeletal muscle tissue engineering. J. Tissue Eng. Regen. Med. 3, 407–415 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Mertens, J. P., Sugg, K. B., Lee, J. D. & Larkin, L. M. Engineering muscle constructs for the creation of functional engineered musculoskeletal tissue. Regen. Med. 9, 89–100 (2014).

    Article  CAS  PubMed  Google Scholar 

  107. Cittadella Vigodarzere, G. & Mantero, S. Skeletal muscle tissue engineering: strategies for volumetric constructs. Front. Physiol. 5, 362 (2014).

    Article  PubMed Central  PubMed  Google Scholar 

  108. Mase, V. J. Jr et al. Clinical application of an acellular biologic scaffold for surgical repair of a large, traumatic quadriceps femoris muscle defect. Orthopedics 33, 511 (2010).

    PubMed  Google Scholar 

  109. Sicari, B. M. et al. An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss. Sci. Transl. Med. 6, 234ra58 (2014).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  110. Hoque, M. E., Chuan, Y. L. & Pashby, I. Extrusion based rapid prototyping technique: an advanced platform for tissue engineering scaffold fabrication. Biopolymers 97, 83–93 (2012).

    Article  CAS  PubMed  Google Scholar 

  111. Rengier, F. et al. 3D printing based on imaging data: review of medical applications. Int. J. Comput. Assist. Radiol. Surg. 5, 335–341 (2010).

    Article  CAS  PubMed  Google Scholar 

  112. Ma, B., Xie, J., Jiang, J., Shuler, F. D. & Bartlett, D. E. Rational design of nanofiber scaffolds for orthopedic tissue repair and regeneration. Nanomedicine (Lond.) 8, 1459–1481 (2013).

    Article  CAS  Google Scholar 

  113. Maude, S., Ingham, E. & Aggeli, A. Biomimetic self-assembling peptides as scaffolds for soft tissue engineering. Nanomedicine (Lond.) 8, 823–847 (2013).

    Article  CAS  Google Scholar 

  114. Holzapfel, B. M. et al. How smart do biomaterials need to be? A translational science and clinical point of view. Adv. Drug Deliv. Rev. 65, 581–603 (2013).

    Article  CAS  PubMed  Google Scholar 

  115. Chen, W. et al. Human embryonic stem cell-derived mesenchymal stem cell seeding on calcium phosphate cement-chitosan-RGD scaffold for bone repair. Tissue Eng. Part A 19, 915–927 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  116. Chaisri, P., Chingsungnoen, A. & Siri, S. Repetitive Gly-Leu-Lys-Gly-Glu-Asn-Arg-Gly-Asp peptide derived from collagen and fibronectin for improving cell-scaffold interaction. Appl. Biochem. Biotechnol. http://dx.doi.org/10.1007/s12010-014-1388-y (2014).

  117. Bertassoni, L. E. et al. Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip 14, 2202–2211 (2014).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  118. Sakaguchi, K. et al. In vitro engineering of vascularized tissue surrogates. Sci. Rep. 3, 1316 (2013).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. Sekine, H. et al. In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat. Commun. 4, 1399 (2013).

    Article  CAS  PubMed  Google Scholar 

  120. Eweida, A. M. et al. Enhancing mandibular bone regeneration and perfusion via axial vascularization of scaffolds. Clin. Oral Investig. 18, 1671–1678 (2014).

    Article  PubMed  Google Scholar 

  121. Kokemüller, H. et al. En bloc prefabrication of vascularized bioartificial bone grafts in sheep and complete workflow for custom-made transplants. Int. J. Oral Maxillofac. Surg. 43, 163–172 (2014).

    Article  PubMed  Google Scholar 

  122. Kosuge, D., Khan, W. S., Haddad, B. & Marsh, D. Biomaterials and scaffolds in bone and musculoskeletal engineering. Curr. Stem Cell Res. Ther. 8, 185–191 (2013).

    Article  CAS  PubMed  Google Scholar 

  123. Rowland, C. R., Little, D. & Guilak, F. Factors influencing the long-term behavior of extracellular matrix-derived scaffolds for musculoskeletal soft tissue repair. J. Long Term Eff. Med. Implants 22, 181–193 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  124. Turner, N. J. & Badylak, S. F. Biologic scaffolds for musculotendinous tissue repair. Eur. Cell. Mater. 25, 130–143 (2013).

    Article  CAS  PubMed  Google Scholar 

  125. Chan, B. P. & Leong, K. W. Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur. Spine J. 17 (Suppl. 4), 467–479 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  126. O'Brien, F. J. Biomaterials & scaffolds for tissue engineering. Materials Today 14, 88–95 (2011).

    Article  CAS  Google Scholar 

  127. Polo-Corrales, L., Latorre-Esteves, M. & Ramirez-Vick, J. E. Scaffold design for bone regeneration. J. Nanosci. Nanotechnol. 14, 15–56 (2014).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Tevlin, R. et al. Biomaterials for craniofacial bone engineering. J. Dent. Res. 93, 1187–1195 (2014).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  129. Bobe, K. et al. In vitro and in vivo evaluation of biodegradable, open-porous scaffolds made of sintered magnesium W4 short fibres. Acta Biomater. 9, 8611–8623 (2013).

    Article  CAS  PubMed  Google Scholar 

  130. Chou, D. T. et al. Novel processing of iron-manganese alloy-based biomaterials by inkjet 3-D printing. Acta Biomater. 9, 8593–8603 (2013).

    Article  CAS  PubMed  Google Scholar 

  131. Matassi, F., Botti, A., Sirleo, L., Carulli, C. & Innocenti, M. Porous metal for orthopedics implants. Clin. Cases Miner. Bone Metab. 10, 111–115 (2013).

    PubMed Central  PubMed  Google Scholar 

  132. Brauker, J. H. et al. Neovascularization of synthetic membranes directed by membrane microarchitecture. J. Biomed. Mater. Res. 29, 1517–1524 (1995).

    Article  CAS  PubMed  Google Scholar 

  133. Klawitter, J. & Hulbert, S. F. Application of porous ceramics for the attachment of load-bearing internal orthopedic applications. J. Biomed. Mater. Res. 5, 161–229 (1971).

    Article  Google Scholar 

  134. Whang, K et al. Engineering bone regeneration with bioabsorbable scaffolds with novel microarchitecture. Tissue Eng. 5, 35–51 (1999).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery and Orthopedic Research Laboratory, Feinstein Institute for Medical Research and North Shore-LIJ Health System, 350 Community Drive, Manhasset, 11030, NY, USA

    Benjamin D. Smith & Daniel A. Grande

Authors
  1. Benjamin D. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel A. Grande
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed equally to researching data for the article, providing a substantial contribution to discussions of the content, writing the article, and to the review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Benjamin D. Smith.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Smith, B., Grande, D. The current state of scaffolds for musculoskeletal regenerative applications. Nat Rev Rheumatol 11, 213–222 (2015). https://doi.org/10.1038/nrrheum.2015.27

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2015.27

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research