Skip to main content
Top
Published in: Journal of Orthopaedic Surgery and Research 1/2019

Open Access 01-12-2019 | Research article

Autologous stem cell-derived chondrocyte implantation with bio-targeted microspheres for the treatment of osteochondral defects

Authors: Murat Bozkurt, Mehmet Doğan Aşık, Safa Gürsoy, Mustafa Türk, Siyami Karahan, Berrak Gümüşkaya, Mustafa Akkaya, Mehmet Emin Şimşek, Nurdan Cay, Metin Doğan

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2019

Login to get access

Abstract

Background

Chondral injury is a common problem around the world. Currently, there are several treatment strategies for these types of injuries. The possible complications and problems associated with conventional techniques lead us to investigate a minimally invasive and biotechnological alternative treatment. Combining tissue-engineering and microencapsulation technologies provide new direction for the development of biotechnological solutions. The aim of this study is to develop a minimal invasive tissue-engineering approach, using bio-targeted microspheres including autologous cells, for the treatment of the cartilage lesions.

Method

In this study, a total of 28 sheeps of Akkaraman breed were randomly assigned to one of the following groups: control (group 1), microfracture (group 2), scaffold (group 3), and microsphere (group 4). Microspheres and scaffold group animals underwent adipose tissue collection prior to the treatment surgery. Mesenchymal cells collected from adipose tissue were differentiated into chondrocytes and encapsulated with scaffolds and microspheres. Osteochondral damage was conducted in the right knee joint of the sheep to create an animal model and all animals treated according to study groups.

Results

Both macroscopic and radiologic examination showed that groups 3 and 4 have resulted better compared to the control and microfracture groups. Moreover, histologic assessments indicate hyaline-like cartilage formations in groups 3 and 4.

Conclusion

In conclusion, we believe that the bio-targeted microspheres can be a more effective, easier, and safer approach for cartilage tissue engineering compared to previous alternatives.
Literature
1.
go back to reference Årøen A, Løken S, Heir S, Alvik E, Ekeland A, Granlund OG, et al. Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med. 2004;32(1):211–5.PubMedCrossRef Årøen A, Løken S, Heir S, Alvik E, Ekeland A, Granlund OG, et al. Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med. 2004;32(1):211–5.PubMedCrossRef
2.
go back to reference Curl WW, Krome J, Gordon ES, Rushing J, Smith BP, Poehling GG. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997;13(4):456–60.PubMedCrossRef Curl WW, Krome J, Gordon ES, Rushing J, Smith BP, Poehling GG. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997;13(4):456–60.PubMedCrossRef
3.
go back to reference Widuchowski W, Widuchowski J, Trzaska T. Articular cartilage defects: study of 25,124 knee arthroscopies. Knee. 2007;14(3):177–82.PubMedCrossRef Widuchowski W, Widuchowski J, Trzaska T. Articular cartilage defects: study of 25,124 knee arthroscopies. Knee. 2007;14(3):177–82.PubMedCrossRef
4.
go back to reference Buckwalter J, Mankin H. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 1998;47:487–504.PubMed Buckwalter J, Mankin H. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 1998;47:487–504.PubMed
5.
go back to reference Iwasaki N, Kato H, Kamishima T, Suenaga N, Minami A. Donor site evaluation after autologous osteochondral mosaicplasty for cartilaginous lesions of the elbow joint. Am J Sports Med. 2007;35(12):2096–100.PubMedCrossRef Iwasaki N, Kato H, Kamishima T, Suenaga N, Minami A. Donor site evaluation after autologous osteochondral mosaicplasty for cartilaginous lesions of the elbow joint. Am J Sports Med. 2007;35(12):2096–100.PubMedCrossRef
6.
go back to reference Bartlett W, Gooding C, Carrington R, Skinner J, Briggs T, Bentley G. Autologous chondrocyte implantation at the knee using a bilayer collagen membrane with bone graft: a preliminary report. J Bone Joint Surg Br. 2005;87(3):330–2.PubMedCrossRef Bartlett W, Gooding C, Carrington R, Skinner J, Briggs T, Bentley G. Autologous chondrocyte implantation at the knee using a bilayer collagen membrane with bone graft: a preliminary report. J Bone Joint Surg Br. 2005;87(3):330–2.PubMedCrossRef
7.
go back to reference Bartlett W, Skinner J, Gooding C, Carrington R, Flanagan A, Briggs T, et al. Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J Bone Joint Surg Br. 2005;87(5):640–5.PubMedCrossRef Bartlett W, Skinner J, Gooding C, Carrington R, Flanagan A, Briggs T, et al. Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J Bone Joint Surg Br. 2005;87(5):640–5.PubMedCrossRef
8.
go back to reference Behrens P, Bitter T, Kurz B, Russlies M. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)—5-year follow-up. Knee. 2006;13(3):194–202.PubMedCrossRef Behrens P, Bitter T, Kurz B, Russlies M. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)—5-year follow-up. Knee. 2006;13(3):194–202.PubMedCrossRef
9.
go back to reference Brun P, Dickinson SC, Zavan B, Cortivo R, Hollander AP, Abatangelo G. Characteristics of repair tissue in second-look and third-look biopsies from patients treated with engineered cartilage: relationship to symptomatology and time after implantation. Arthritis Res Ther. 2008;10(6):R132.PubMedPubMedCentralCrossRef Brun P, Dickinson SC, Zavan B, Cortivo R, Hollander AP, Abatangelo G. Characteristics of repair tissue in second-look and third-look biopsies from patients treated with engineered cartilage: relationship to symptomatology and time after implantation. Arthritis Res Ther. 2008;10(6):R132.PubMedPubMedCentralCrossRef
10.
go back to reference Iwasa J, Engebretsen L, Shima Y, Ochi M. Clinical application of scaffolds for cartilage tissue engineering. Knee Surg Sports Traumatol Arthrosc. 2009;17(6):561–77.PubMedCrossRef Iwasa J, Engebretsen L, Shima Y, Ochi M. Clinical application of scaffolds for cartilage tissue engineering. Knee Surg Sports Traumatol Arthrosc. 2009;17(6):561–77.PubMedCrossRef
11.
go back to reference Murua A, Portero A, Orive G, Hernández RM, de Castro M, Pedraz JL. Cell microencapsulation technology: towards clinical application. J Control Release. 2008;132(2):76–83.PubMedCrossRef Murua A, Portero A, Orive G, Hernández RM, de Castro M, Pedraz JL. Cell microencapsulation technology: towards clinical application. J Control Release. 2008;132(2):76–83.PubMedCrossRef
12.
go back to reference Buckwalter J. Osteoarthritis and articular cartilage use, disuse, and abuse: experimental studies. J Rheumatol Suppl. 1995;43:13–5.PubMed Buckwalter J. Osteoarthritis and articular cartilage use, disuse, and abuse: experimental studies. J Rheumatol Suppl. 1995;43:13–5.PubMed
13.
go back to reference Radin EL, Martin RB, Burr DB, Caterson B, Boyd RD, Goodwin C. Effects of mechanical loading on the tissues of the rabbit knee. J Orthop Res. 1984;2(3):221–34.PubMedCrossRef Radin EL, Martin RB, Burr DB, Caterson B, Boyd RD, Goodwin C. Effects of mechanical loading on the tissues of the rabbit knee. J Orthop Res. 1984;2(3):221–34.PubMedCrossRef
14.
go back to reference Hoch D, Grodzinsky A, Koob T, Albert M, Eyre D. Early changes in material properties of rabbit articular cartilage after meniscectomy. J Orthop Res. 1983;1(1):4–12.PubMedCrossRef Hoch D, Grodzinsky A, Koob T, Albert M, Eyre D. Early changes in material properties of rabbit articular cartilage after meniscectomy. J Orthop Res. 1983;1(1):4–12.PubMedCrossRef
16.
go back to reference Dickinson SC, Sims TJ, Pittarello L, Soranzo C, Pavesio A, Hollander AP. Quantitative outcome measures of cartilage repair in patients treated by tissue engineering. Tissue Eng. 2005;11(1–2):277–87.PubMedCrossRef Dickinson SC, Sims TJ, Pittarello L, Soranzo C, Pavesio A, Hollander AP. Quantitative outcome measures of cartilage repair in patients treated by tissue engineering. Tissue Eng. 2005;11(1–2):277–87.PubMedCrossRef
17.
go back to reference Dunkin BS, Lattermann C. New and emerging techniques in cartilage repair: matrix-induced autologous chondrocyte implantation. Oper Tech Sports Med. 2013;21(2):100–7.PubMedPubMedCentralCrossRef Dunkin BS, Lattermann C. New and emerging techniques in cartilage repair: matrix-induced autologous chondrocyte implantation. Oper Tech Sports Med. 2013;21(2):100–7.PubMedPubMedCentralCrossRef
18.
go back to reference Goyal D, Goyal A, Keyhani S, Lee EH, Hui JH. Evidence-based status of second-and third-generation autologous chondrocyte implantation over first generation: a systematic review of level I and II studies. Arthroscopy. 2013;29(11):1872–8.PubMedCrossRef Goyal D, Goyal A, Keyhani S, Lee EH, Hui JH. Evidence-based status of second-and third-generation autologous chondrocyte implantation over first generation: a systematic review of level I and II studies. Arthroscopy. 2013;29(11):1872–8.PubMedCrossRef
19.
go back to reference Hettrich CM, Crawford D, Rodeo SA. Cartilage repair: third-generation cell-based technologies—basic science, surgical techniques, clinical outcomes. Sports Med Arthrosc Rev. 2008;16(4):230–5.PubMedCrossRef Hettrich CM, Crawford D, Rodeo SA. Cartilage repair: third-generation cell-based technologies—basic science, surgical techniques, clinical outcomes. Sports Med Arthrosc Rev. 2008;16(4):230–5.PubMedCrossRef
20.
go back to reference Hollander AP, Dickinson SC, Sims TJ, Brun P, Cortivo R, Kon E, et al. Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees. Tissue Eng. 2006;12(7):1787–98.PubMedCrossRef Hollander AP, Dickinson SC, Sims TJ, Brun P, Cortivo R, Kon E, et al. Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees. Tissue Eng. 2006;12(7):1787–98.PubMedCrossRef
21.
go back to reference Kessler MW, Ackerman G, Dines JS, Grande D. Emerging technologies and fourth generation issues in cartilage repair. Sports Med Arthrosc Rev. 2008;16(4):246–54.PubMedCrossRef Kessler MW, Ackerman G, Dines JS, Grande D. Emerging technologies and fourth generation issues in cartilage repair. Sports Med Arthrosc Rev. 2008;16(4):246–54.PubMedCrossRef
22.
go back to reference Mollon B, Kandel R, Chahal J, Theodoropoulos J. The clinical status of cartilage tissue regeneration in humans. Osteoarthr Cartil. 2013;21(12):1824–33.CrossRef Mollon B, Kandel R, Chahal J, Theodoropoulos J. The clinical status of cartilage tissue regeneration in humans. Osteoarthr Cartil. 2013;21(12):1824–33.CrossRef
23.
go back to reference Snir N, Wolfson TS, Hamula MJ, Gyftopoulos S, Meislin RJ. Arthroscopic anatomic humeral head reconstruction with osteochondral allograft transplantation for large Hill-Sachs lesions. Arthrosc Tech. 2013;2(3):e289–e93.PubMedPubMedCentralCrossRef Snir N, Wolfson TS, Hamula MJ, Gyftopoulos S, Meislin RJ. Arthroscopic anatomic humeral head reconstruction with osteochondral allograft transplantation for large Hill-Sachs lesions. Arthrosc Tech. 2013;2(3):e289–e93.PubMedPubMedCentralCrossRef
24.
go back to reference Desando G, Giavaresi G, Cavallo C, Bartolotti I, Sartoni F, Nicoli Aldini N, et al. Autologous bone marrow concentrate in a sheep model of osteoarthritis: new perspectives for cartilage and meniscus repair. Tissue Eng Part C Methods. 2016;22(6):608–19.PubMedCrossRef Desando G, Giavaresi G, Cavallo C, Bartolotti I, Sartoni F, Nicoli Aldini N, et al. Autologous bone marrow concentrate in a sheep model of osteoarthritis: new perspectives for cartilage and meniscus repair. Tissue Eng Part C Methods. 2016;22(6):608–19.PubMedCrossRef
25.
go back to reference Ude CC, Sulaiman SB, Min-Hwei N, Hui-Cheng C, Ahmad J, Yahaya NM, et al. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model. PLoS One. 2014;9(6):e98770.PubMedPubMedCentralCrossRef Ude CC, Sulaiman SB, Min-Hwei N, Hui-Cheng C, Ahmad J, Yahaya NM, et al. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model. PLoS One. 2014;9(6):e98770.PubMedPubMedCentralCrossRef
26.
go back to reference Delling U, Brehm W, Ludewig E, Winter K, Jülke H. Longitudinal evaluation of effects of intra-articular mesenchymal stromal cell administration for the treatment of osteoarthritis in an ovine model. Cell Transplant. 2015;24(11):2391–407.PubMedCrossRef Delling U, Brehm W, Ludewig E, Winter K, Jülke H. Longitudinal evaluation of effects of intra-articular mesenchymal stromal cell administration for the treatment of osteoarthritis in an ovine model. Cell Transplant. 2015;24(11):2391–407.PubMedCrossRef
27.
go back to reference Guillén-García P, Rodríguez-Iñigo E, Guillén-Vicente I, Caballero-Santos R, Guillén-Vicente M, Abelow S, et al. Increasing the dose of autologous chondrocytes improves articular cartilage repair: histological and molecular study in the sheep animal model. Cartilage. 2014;5(2):114–22.PubMedPubMedCentralCrossRef Guillén-García P, Rodríguez-Iñigo E, Guillén-Vicente I, Caballero-Santos R, Guillén-Vicente M, Abelow S, et al. Increasing the dose of autologous chondrocytes improves articular cartilage repair: histological and molecular study in the sheep animal model. Cartilage. 2014;5(2):114–22.PubMedPubMedCentralCrossRef
28.
go back to reference Marlovits S, Striessnig G, Resinger CT, Aldrian SM, Vecsei V, Imhof H, et al. Definition of pertinent parameters for the evaluation of articular cartilage repair tissue with high-resolution magnetic resonance imaging. Eur J Radiol. 2004;52(3):310–9.PubMedCrossRef Marlovits S, Striessnig G, Resinger CT, Aldrian SM, Vecsei V, Imhof H, et al. Definition of pertinent parameters for the evaluation of articular cartilage repair tissue with high-resolution magnetic resonance imaging. Eur J Radiol. 2004;52(3):310–9.PubMedCrossRef
29.
go back to reference Mats Brittberg CAP, Gambardella R, Hungary LH, Hauselmann HJ, Jakon RP, Levine D, Lohmander S, Mandelbaum BR, Peterson L, et al. ICRS cartilage injury evaluation package. In: Proceedings of the 3rd ICRS Meeting; Göteborg, Sweden; 2000. Mats Brittberg CAP, Gambardella R, Hungary LH, Hauselmann HJ, Jakon RP, Levine D, Lohmander S, Mandelbaum BR, Peterson L, et al. ICRS cartilage injury evaluation package. In: Proceedings of the 3rd ICRS Meeting; Göteborg, Sweden; 2000.
30.
go back to reference Chen C-Y, Ke C-J, Yen K-C, Hsieh H-C, Sun J-S, Lin F-H. 3D porous calcium-alginate scaffolds cell culture system improved human osteoblast cell clusters for cell therapy. Theranostics. 2015;5(6):643–55.PubMedPubMedCentralCrossRef Chen C-Y, Ke C-J, Yen K-C, Hsieh H-C, Sun J-S, Lin F-H. 3D porous calcium-alginate scaffolds cell culture system improved human osteoblast cell clusters for cell therapy. Theranostics. 2015;5(6):643–55.PubMedPubMedCentralCrossRef
31.
go back to reference Cherubino P, Grassi F, Bulgheroni P, Ronga M. Autologous chondrocyte implantation using a bilayer collagen membrane: a preliminary report. J Orthop Surg. 2003;11(1):10–5.CrossRef Cherubino P, Grassi F, Bulgheroni P, Ronga M. Autologous chondrocyte implantation using a bilayer collagen membrane: a preliminary report. J Orthop Surg. 2003;11(1):10–5.CrossRef
32.
go back to reference D’Anchise R, Manta N, Prospero E, Bevilacqua C, Gigante A. Autologous implantation of chondrocytes on a solid collagen scaffold: clinical and histological outcomes after two years of follow-up. J Orthop Traumatol. 2005;6(1):36–43.CrossRef D’Anchise R, Manta N, Prospero E, Bevilacqua C, Gigante A. Autologous implantation of chondrocytes on a solid collagen scaffold: clinical and histological outcomes after two years of follow-up. J Orthop Traumatol. 2005;6(1):36–43.CrossRef
33.
go back to reference Ronga M, Grassi FA, Bulgheroni P. Arthroscopic autologous chondrocyte implantation for the treatment of a chondral defect in the tibial plateau of the knee. Arthroscopy. 2004;20(1):79–84.PubMedCrossRef Ronga M, Grassi FA, Bulgheroni P. Arthroscopic autologous chondrocyte implantation for the treatment of a chondral defect in the tibial plateau of the knee. Arthroscopy. 2004;20(1):79–84.PubMedCrossRef
34.
go back to reference Ronga M, Grassi FA, Manelli A, Bulgheroni P. Tissue engineering techniques for the treatment of a complex knee injury. Arthroscopy. 2006;22(5):576. e1–3.CrossRef Ronga M, Grassi FA, Manelli A, Bulgheroni P. Tissue engineering techniques for the treatment of a complex knee injury. Arthroscopy. 2006;22(5):576. e1–3.CrossRef
35.
go back to reference Amin A, Bartlett W, Gooding C, Sood M, Skinner J, Carrington R, et al. The use of autologous chondrocyte implantation following and combined with anterior cruciate ligament reconstruction. Int Orthop. 2006;30(1):48–53.PubMedCrossRef Amin A, Bartlett W, Gooding C, Sood M, Skinner J, Carrington R, et al. The use of autologous chondrocyte implantation following and combined with anterior cruciate ligament reconstruction. Int Orthop. 2006;30(1):48–53.PubMedCrossRef
36.
go back to reference Ronga M, Grassi F, Montoli C, Bulgheroni P, Genovese E, Cherubino P. Treatment of deep cartilage defects of the ankle with matrix-induced autologous chondrocyte implantation (MACI). Foot Ankle Surg. 2005;11(1):29–33.CrossRef Ronga M, Grassi F, Montoli C, Bulgheroni P, Genovese E, Cherubino P. Treatment of deep cartilage defects of the ankle with matrix-induced autologous chondrocyte implantation (MACI). Foot Ankle Surg. 2005;11(1):29–33.CrossRef
37.
go back to reference Hayami JW, Waldman SD, Amsden BG. A photocurable hydrogel/elastomer composite scaffold with bi-continuous morphology for cell encapsulation. Macromol Biosci. 2011;11(12):1672–83.PubMedCrossRef Hayami JW, Waldman SD, Amsden BG. A photocurable hydrogel/elastomer composite scaffold with bi-continuous morphology for cell encapsulation. Macromol Biosci. 2011;11(12):1672–83.PubMedCrossRef
38.
go back to reference Wang QG, Nguyen B, Thomas CR, Zhang Z, El Haj AJ, Kuiper NJ. Molecular profiling of single cells in response to mechanical force: comparison of chondrocytes, chondrons and encapsulated chondrocytes. Biomaterials. 2010;31(7):1619–25.PubMedCrossRef Wang QG, Nguyen B, Thomas CR, Zhang Z, El Haj AJ, Kuiper NJ. Molecular profiling of single cells in response to mechanical force: comparison of chondrocytes, chondrons and encapsulated chondrocytes. Biomaterials. 2010;31(7):1619–25.PubMedCrossRef
39.
go back to reference Hossain KMZ, Patel U, Ahmed I. Development of microspheres for biomedical applications: a review. Prog Biomater. 2015;4(1):1–19.PubMedCrossRef Hossain KMZ, Patel U, Ahmed I. Development of microspheres for biomedical applications: a review. Prog Biomater. 2015;4(1):1–19.PubMedCrossRef
40.
go back to reference Chan BP, Hui TY, Wong MY, Yip KHK, Chan GCF. Mesenchymal stem cell–encapsulated collagen microspheres for bone tissue engineering. Tissue Eng Part C Methods. 2009;16(2):225–35.CrossRef Chan BP, Hui TY, Wong MY, Yip KHK, Chan GCF. Mesenchymal stem cell–encapsulated collagen microspheres for bone tissue engineering. Tissue Eng Part C Methods. 2009;16(2):225–35.CrossRef
41.
go back to reference Gupta V, Khan Y, Berkland CJ, Laurencin CT, Detamore MS. Microsphere-based scaffolds in regenerative engineering. Annu Rev Biomed Eng. 2017;19:135–61.PubMedCrossRef Gupta V, Khan Y, Berkland CJ, Laurencin CT, Detamore MS. Microsphere-based scaffolds in regenerative engineering. Annu Rev Biomed Eng. 2017;19:135–61.PubMedCrossRef
42.
go back to reference Wang M, Yuan Z, Ma N, Hao C, Guo W, Zou G, et al. Advances and prospects in stem cells for cartilage regeneration. Stem Cells Int. 2017;2017:4130607.PubMedPubMedCentral Wang M, Yuan Z, Ma N, Hao C, Guo W, Zou G, et al. Advances and prospects in stem cells for cartilage regeneration. Stem Cells Int. 2017;2017:4130607.PubMedPubMedCentral
43.
go back to reference Pot MW, van Kuppevelt TH, Gonzales VK, Buma P, IntHout J, de Vries RB, et al. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies. PeerJ. 2017;5:e3927.PubMedPubMedCentralCrossRef Pot MW, van Kuppevelt TH, Gonzales VK, Buma P, IntHout J, de Vries RB, et al. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies. PeerJ. 2017;5:e3927.PubMedPubMedCentralCrossRef
Metadata
Title
Autologous stem cell-derived chondrocyte implantation with bio-targeted microspheres for the treatment of osteochondral defects
Authors
Murat Bozkurt
Mehmet Doğan Aşık
Safa Gürsoy
Mustafa Türk
Siyami Karahan
Berrak Gümüşkaya
Mustafa Akkaya
Mehmet Emin Şimşek
Nurdan Cay
Metin Doğan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2019
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-019-1434-0

Other articles of this Issue 1/2019

Journal of Orthopaedic Surgery and Research 1/2019 Go to the issue