Abstract
Injuries to articular cartilage and menisci can lead to cartilage degeneration that ultimately results in arthritis. Different forms of arthritis affect ~50 million people in the USA alone, and it is therefore crucial to identify methods that will halt or slow the progression to arthritis, starting with the initiating events of cartilage and meniscus defects. The surgical approaches in current use have a limited capacity for tissue regeneration and yield only short-term relief of symptoms. Tissue engineering approaches are emerging as alternatives to current surgical methods for cartilage and meniscus repair. Several cell-based and tissue-engineered products are currently in clinical trials for cartilage lesions and meniscal tears, opening new avenues for cartilage and meniscus regeneration. This Review provides a summary of surgical techniques, including tissue-engineered products, that are currently in clinical use, as well as a discussion of state-of-the-art tissue engineering strategies and technologies that are being developed for use in articular cartilage and meniscus repair and regeneration. The obstacles to clinical translation of these strategies are also included to inform the development of innovative tissue engineering approaches.
Key points
-
Current cartilage repair techniques include surgery and cell-based therapies for articular cartilage, and surgery for meniscus repair; however, such treatments have limited capacity to induce regeneration.
-
Tissue engineering strategies to create cartilage using a variety of cell sources and exogenous stimuli have made advances towards replicating the native architecture and functional properties of cartilage.
-
Most cell-based tissue engineering products currently in clinical trials are indicated for knee articular cartilage, with very few indicated for hip cartilage or the meniscus.
-
Allogeneic and non-articulating cartilage might serve as additional cell sources for engineered articular cartilage and meniscus products.
-
The pro-inflammatory environment of arthritic joints and issues surrounding neotissue integration need to be addressed to maximize the clinical translation of new tissue-engineered products.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Centers for Disease Control and Prevention. Arthritis-related statistics. CDC https://www.cdc.gov/arthritis/data_statistics/arthritis-related-stats.htm (2018).
Centers for Disease Control and Prevention. Osteoarthritis. CDC https://www.cdc.gov/arthritis/basics/osteoarthritis.htm (2019).
Wilder, F. V., Hall, B. J., Barrett, J. P. Jr & Lemrow, N. B. History of acute knee injury and osteoarthritis of the knee: a prospective epidemiological assessment. The Clearwater Osteoarthritis Study. Osteoarthritis Cartilage 10, 611–616 (2002).
Wellsandt, E. et al. Decreased knee joint loading associated with early knee osteoarthritis after anterior cruciate ligament injury. Am. J. Sports Med. 44, 143–151 (2016).
Lohmander, L. S., Englund, P. M., Dahl, L. L. & Roos, E. M. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am. J. Sports Med. 35, 1756–1769 (2007).
Cross, M. et al. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Ann. Rheum. Dis. 73, 1323–1330 (2014).
Helmick, C. G. et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 58, 15–25 (2008).
Losina, E. et al. Lifetime medical costs of knee osteoarthritis management in the United States: impact of extending indications for total knee arthroplasty. Arthritis Care Res. 67, 203–215 (2015).
Birnbaum, H. et al. Societal cost of rheumatoid arthritis patients in the US. Curr. Med. Res. Opin. 26, 77–90 (2010).
Hochberg, M. C. et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 64, 465–474 (2012).
Singh, J. A. et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 68, 1–25 (2016).
Makris, E. A., Gomoll, A. H., Malizos, K. N., Hu, J. C. & Athanasiou, K. A. Repair and tissue engineering techniques for articular cartilage. Nat. Rev. Rheumatol. 11, 21–34 (2015).
Athanasiou, K. A., Darling, E. M., Hu, J. C., DuRaine, G. D. & Reddi, A. H. Articular Cartilage 2nd edn Ch. 4 257–389 (Taylor & Francis, 2016).
Moran, C. J., Busilacchi, A., Lee, C. A., Athanasiou, K. A. & Verdonk, P. C. Biological augmentation and tissue engineering approaches in meniscus surgery. Arthroscopy 31, 944–955 (2015).
Athanasiou, K. A. & Sanchez-Adams, J. Engineering the Knee Meniscus Ch. 3 35–53 (Morgan & Claypool, 2009).
Curl, W. W. et al. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy 13, 456–460 (1997).
Hjelle, K., Solheim, E., Strand, T., Muri, R. & Brittberg, M. Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy 18, 730–734 (2002).
Flanigan, D. C., Harris, J. D., Trinh, T. Q., Siston, R. A. & Brophy, R. H. Prevalence of chondral defects in athletes’ knees: a systematic review. Med. Sci. Sports Exerc. 42, 1795–1801 (2010).
Richter, D. L., Schenck, R. C. Jr, Wascher, D. C. & Treme, G. Knee articular cartilage repair and restoration techniques: a review of the literature. Sports Health 8, 153–160 (2016).
Bedi, A., Feeley, B. T. & Williams, R. J. 3rd. Management of articular cartilage defects of the knee. J. Bone Joint Surg. Am. 92, 994–1009 (2010).
Steadman, J. R., Rodkey, W. G. & Rodrigo, J. J. Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin. Orthop. Relat. Res. 391, S362–S369 (2001).
Gudas, R. et al. Ten-year follow-up of a prospective, randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint of athletes. Am. J. Sports Med. 40, 2499–2508 (2012).
Solheim, E., Hegna, J., Strand, T., Harlem, T. & Inderhaug, E. Randomized study of long-term (15–17 years) outcome after microfracture versus mosaicplasty in knee articular cartilage defects. Am. J. Sports Med. 46, 826–831 (2018).
Albright, J. C. & Daoud, A. K. Microfracture and microfracture plus. Clin. Sports Med. 36, 501–507 (2017).
Gao, L., Orth, P., Cucchiarini, M. & Madry, H. Autologous matrix-induced chondrogenesis: a systematic review of the clinical evidence. Am. J. Sports Med. 47, 222–231 (2017).
Krych, A. J. et al. Return to sport after the surgical management of articular cartilage lesions in the knee: a meta-analysis. Knee Surg. Sports Traumatol. Arthrosc. 25, 3186–3196 (2017).
Hangody, L. et al. Autologous osteochondral mosaicplasty. Surgical technique. J. Bone Joint Surg. Am. 86-A, S65–S72 (2004).
Arzi, B. et al. Cartilage immunoprivilege depends on donor source and lesion location. Acta Biomater. 23, 72–81 (2015).
Koh, J. L., Kowalski, A. & Lautenschlager, E. The effect of angled osteochondral grafting on contact pressure: a biomechanical study. Am. J. Sports Med. 34, 116–119 (2006).
Koh, J. L., Wirsing, K., Lautenschlager, E. & Zhang, L. O. The effect of graft height mismatch on contact pressure following osteochondral grafting: a biomechanical study. Am. J. Sports Med. 32, 317–320 (2004).
Cook, J. L. et al. Importance of donor chondrocyte viability for osteochondral allografts. Am. J. Sports Med. 44, 1260–1268 (2016).
Williams, R. J. 3rd, Ranawat, A. S., Potter, H. G., Carter, T. & Warren, R. F. Fresh stored allografts for the treatment of osteochondral defects of the knee. J. Bone Joint Surg. Am. 89, 718–726 (2007).
Levy, Y. D., Gortz, S., Pulido, P. A., McCauley, J. C. & Bugbee, W. D. Do fresh osteochondral allografts successfully treat femoral condyle lesions? Clin. Orthop. Relat. Res. 471, 231–237 (2013).
Hangody, L. & Fules, P. Autologous osteochondral mosaicplasty for the treatment of full-thickness defects of weight-bearing joints: ten years of experimental and clinical experience. J. Bone Joint Surg. Am. 85-A, S25–S32 (2003).
Balazs, G. C. et al. Return to play among elite basketball players after osteochondral allograft transplantation of full-thickness cartilage lesions. Orthop. J. Sports Med. 6, 2325967118786941 (2018).
Hinckel, B. B., Gomoll, A. H. & Farr, J. 2nd Cartilage restoration in the patellofemoral joint. Am. J. Orthop. 46, 217–222 (2017).
Dunkin, B. S. & Lattermann, C. New and emerging techniques in cartilage repair: MACI. Oper. Tech. Sports Med. 21, 100–107 (2013).
Ebert, J. R., Fallon, M., Wood, D. J. & Janes, G. C. A Prospective clinical and radiological evaluation at 5 years after arthroscopic matrix-induced autologous chondrocyte implantation. Am. J. Sports Med. 45, 59–69 (2017).
Ebert, J. R., Fallon, M., Smith, A., Janes, G. C. & Wood, D. J. Prospective clinical and radiologic evaluation of patellofemoral matrix-induced autologous chondrocyte implantation. Am. J. Sports Med. 43, 1362–1372 (2015).
Fillingham, Y. A., Riboh, J. C., Erickson, B. J., Bach, B. R. Jr & Yanke, A. B. Inside-out versus all-inside repair of isolated meniscal tears: an updated systematic review. Am. J. Sports Med. 45, 234–242 (2017).
Barrett, G. R., Field, M. H., Treacy, S. H. & Ruff, C. G. Clinical results of meniscus repair in patients 40 years and older. Arthroscopy 14, 824–829 (1998).
Eggli, S., Wegmuller, H., Kosina, J., Huckell, C. & Jakob, R. P. Long-term results of arthroscopic meniscal repair. An analysis of isolated tears. Am. J. Sports Med. 23, 715–720 (1995).
Kim, S., Bosque, J., Meehan, J. P., Jamali, A. & Marder, R. Increase in outpatient knee arthroscopy in the United States: a comparison of National Surveys of Ambulatory Surgery, 1996 and 2006. J. Bone Joint Surg. Am. 93, 994–1000 (2011).
Papalia, R., Del Buono, A., Osti, L., Denaro, V. & Maffulli, N. Meniscectomy as a risk factor for knee osteoarthritis: a systematic review. Br. Med. Bull. 99, 89–106 (2011).
Abrams, G. D. et al. Trends in meniscus repair and meniscectomy in the United States, 2005–2011. Am. J. Sports Med. 41, 2333–2339 (2013).
Johnson, M. J., Lucas, G. L., Dusek, J. K. & Henning, C. E. Isolated arthroscopic meniscal repair: a long-term outcome study (more than 10 years). Am. J. Sports Med. 27, 44–49 (1999).
Pujol, N., Bohu, Y., Boisrenoult, P., Macdes, A. & Beaufils, P. Clinical outcomes of open meniscal repair of horizontal meniscal tears in young patients. Knee Surg. Sports Traumatol. Arthrosc. 21, 1530–1533 (2013).
Choi, N. H., Kim, T. H., Son, K. M. & Victoroff, B. N. Meniscal repair for radial tears of the midbody of the lateral meniscus. Am. J. Sports Med. 38, 2472–2476 (2010).
Wasserstein, D. et al. A matched-cohort population study of reoperation after meniscal repair with and without concomitant anterior cruciate ligament reconstruction. Am. J. Sports Med. 41, 349–355 (2013).
Hutchinson, I. D., Moran, C. J., Potter, H. G., Warren, R. F. & Rodeo, S. A. Restoration of the meniscus: form and function. Am. J. Sports Med. 42, 987–998 (2014).
Zhang, Z., Arnold, J. A., Williams, T. & McCann, B. Repairs by trephination and suturing of longitudinal injuries in the avascular area of the meniscus in goats. Am. J. Sports Med. 23, 35–41 (1995).
Taylor, S. A. & Rodeo, S. A. Augmentation techniques for isolated meniscal tears. Curr. Rev. Musculoskelet. Med. 6, 95–101 (2013).
Henning, C. E. et al. Arthroscopic meniscal repair using an exogenous fibrin clot. Clin. Orthop. Relat. Res. 252, 64–72 (1990).
Dean, C. S., Chahla, J., Matheny, L. M., Mitchell, J. J. & LaPrade, R. F. Outcomes after biologically augmented isolated meniscal repair with marrow venting are comparable with those after meniscal repair with concomitant anterior cruciate ligament reconstruction. Am. J. Sports Med. 45, 1341–1348 (2017).
Verdonk, R. et al. Indications and limits of meniscal allografts. Injury 44 (Suppl. 1), 21–27 (2013).
Rodeo, S. A. Meniscal allografts—where do we stand? Am. J. Sports Med. 29, 246–261 (2001).
Lee, S. R., Kim, J. G. & Nam, S. W. The tips and pitfalls of meniscus allograft transplantation. Knee Surg. Relat. Res. 24, 137–145 (2012).
Dienst, M., Greis, P. E., Ellis, B. J., Bachus, K. N. & Burks, R. T. Effect of lateral meniscal allograft sizing on contact mechanics of the lateral tibial plateau: an experimental study in human cadaveric knee joints. Am. J. Sports Med. 35, 34–42 (2007).
Vundelinckx, B., Vanlauwe, J. & Bellemans, J. Long-term subjective, clinical, and radiographic outcome evaluation of meniscal allograft transplantation in the knee. Am. J. Sports Med. 42, 1592–1599 (2014).
Lee, S. M. et al. Long-term outcomes of meniscal allograft transplantation with and without extrusion: mean 12.3-year follow-up study. Am. J. Sports Med. 47, 815–821 (2019).
van Tienen, T. G., Hannink, G. & Buma, P. Meniscus replacement using synthetic materials. Clin. Sport Med. 28, 143–156 (2009).
Bulgheroni, E. et al. Long-term outcomes of medial CMI implant versus partial medial meniscectomy in patients with concomitant ACL reconstruction. Knee Surg. Sports Traumatol. Arthrosc. 23, 3221–3227 (2015).
Schuttler, K. F. et al. Midterm follow-up after implantation of a polyurethane meniscal scaffold for segmental medial meniscus loss: maintenance of good clinical and MRI outcome. Knee Surg. Sports Traumatol. Arthrosc. 24, 1478–1484 (2016).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02136901 (2018).
Marinescu, R. & Antoniac, I. in Handbook of Bioceramics and Biocomposite (ed. Antoniac, I. V.) 1–31 (Springer, Cham, 2015).
Kramer, D. E. & Micheli, L. J. Meniscal tears and discoid meniscus in children: diagnosis and treatment. J. Am. Acad. Orthop. Surg. 17, 698–707 (2009).
Adirim, T. A. & Cheng, T. L. Overview of injuries in the young athlete. Sports Med. 33, 75–81 (2003).
Beck, N. A., Lawrence, J. T. R., Nordin, J. D., DeFor, T. A. & Tompkins, M. ACL tears in school-aged children and adolescents over 20 years. Pediatrics 139, e20161877 (2017).
Kreuz, P. C. et al. Is microfracture of chondral defects in the knee associated with different results in patients aged 40 years or younger? Arthroscopy 22, 1180–1186 (2006).
Asik, M., Ciftci, F., Sen, C., Erdil, M. & Atalar, A. The microfracture technique for the treatment of full-thickness articular cartilage lesions of the knee: midterm results. Arthroscopy 24, 1214–1220 (2008).
Mithoefer, K., McAdams, T., Williams, R. J., Kreuz, P. C. & Mandelbaum, B. R. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am. J. Sports Med. 37, 2053–2063 (2009).
Mithoefer, K. et al. The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. J. Bone Joint Surg. Am. 87, 1911–1920 (2005).
Gudas, R. et al. A prospective randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint in young athletes. Arthroscopy 21, 1066–1075 (2005).
Murphy, R. T., Pennock, A. T. & Bugbee, W. D. Osteochondral allograft transplantation of the knee in the pediatric and adolescent population. Am. J. Sports Med. 42, 635–640 (2014).
Frank, R. M. et al. Osteochondral allograft transplantation of the knee: analysis of failures at 5 years. Am. J. Sports Med. 45, 864–874 (2017).
Micheli, L. J. et al. Articular cartilage defects of the distal femur in children and adolescents: treatment with autologous chondrocyte implantation. J. Pediatr. Orthop. 26, 455–460 (2006).
Mithofer, K., Minas, T., Peterson, L., Yeon, H. & Micheli, L. J. Functional outcome of knee articular cartilage repair in adolescent athletes. Am. J. Sports Med. 33, 1147–1153 (2005).
Knutsen, G. et al. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J. Bone Joint Surg. Am. 86, 455–464 (2004).
Saris, D. B. et al. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am. J. Sports Med. 37 (Suppl. 1), 10–19 (2009).
Gudas, R., Stankevicius, E., Monastyreckiene, E., Pranys, D. & Kalesinskas, R. J. Osteochondral autologous transplantation versus microfracture for the treatment of articular cartilage defects in the knee joint in athletes. Knee Surg. Sports Traumatol. Arthrosc. 14, 834–842 (2006).
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).
Noyes, F. R. & Barber-Westin, S. D. Meniscus transplantation: indications, techniques, clinical outcomes. Instr. Course Lect. 54, 341–353 (2005).
Riboh, J. C., Tilton, A. K., Cvetanovich, G. L., Campbell, K. A. & Cole, B. J. Meniscal allograft transplantation in the adolescent population. Arthroscopy 32, 1133–1140 (2016).
Steadman, J. R. et al. Meniscus suture repair: minimum 10-year outcomes in patients younger than 40 years compared with patients 40 and older. Am. J. Sports Med. 43, 2222–2227 (2015).
Rothermel, S. D., Smuin, D. & Dhawan, A. Are outcomes after meniscal repair age dependent? A systematic review. Arthroscopy 34, 979–987 (2018).
Nepple, J. J., Dunn, W. R. & Wright, R. W. Meniscal repair outcomes at greater than five years: a systematic literature review and meta-analysis. J. Bone Joint Surg. Am. 94, 2222–2227 (2012).
Shyh-Chang, N. et al. Lin28 enhances tissue repair by reprogramming cellular metabolism. Cell 155, 778–792 (2013).
Makris, E. A., Hadidi, P. & Athanasiou, K. A. The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials 32, 7411–7431 (2011).
Bhattacharjee, M. et al. Tissue engineering strategies to study cartilage development, degeneration and regeneration. Adv. Drug Deliv. Rev. 84, 107–122 (2015).
Rowland, C. R., Colucci, L. A. & Guilak, F. Fabrication of anatomically-shaped cartilage constructs using decellularized cartilage-derived matrix scaffolds. Biomaterials 91, 57–72 (2016).
Shimomura, K., Rothrauff, B. B. & Tuan, R. S. Region-specific effect of the decellularized meniscus extracellular matrix on mesenchymal stem cell-based meniscus tissue engineering. Am. J. Sports Med. 45, 604–611 (2017).
Liu, M. et al. Injectable hydrogels for cartilage and bone tissue engineering. Bone Res. 5, 17014 (2017).
Guo, T., Lembong, J., Zhang, L. G. & Fisher, J. P. Three-dimensional printing articular cartilage: recapitulating the complexity of native tissue. Tissue Eng. B 23, 225–236 (2017).
Shen, S. et al. 3D printing-based strategies for functional cartilage regeneration. Tissue Eng. B https://doi.org/10.1089/ten.teb.2018.0248 (2019).
Athanasiou, K. A., Eswaramoorthy, R., Hadidi, P. & Hu, J. C. Self-organization and the self-assembling process in tissue engineering. Annu. Rev. Biomed. Eng. 15, 115–136 (2013).
Hu, J. C. & Athanasiou, K. A. A self-assembling process in articular cartilage tissue engineering. Tissue Eng. 12, 969–979 (2006).
Hoben, G. M., Hu, J. C., James, R. A. & Athanasiou, K. A. Self-assembly of fibrochondrocytes and chondrocytes for tissue engineering of the knee meniscus. Tissue Eng. 13, 939–946 (2007).
Ofek, G. et al. Matrix development in self-assembly of articular cartilage. PLoS One 3, e2795 (2008).
Lee, J. K. et al. Tension stimulation drives tissue formation in scaffold-free systems. Nat. Mater. 16, 864–873 (2017).
Elder, B. D. & Athanasiou, K. A. Systematic assessment of growth factor treatment on biochemical and biomechanical properties of engineered articular cartilage constructs. Osteoarthritis Cartilage 17, 114–123 (2009).
Little, C. J., Bawolin, N. K. & Chen, X. Mechanical properties of natural cartilage and tissue-engineered constructs. Tissue Eng. B 17, 213–227 (2011).
Gunja, N. J., Huey, D. J., James, R. A. & Athanasiou, K. A. Effects of agarose mould compliance and surface roughness on self-assembled meniscus-shaped constructs. J. Tissue Eng. Regen. Med. 3, 521–530 (2009).
Makris, E. A., MacBarb, R. F., Paschos, N. K., Hu, J. C. & Athanasiou, K. A. Combined use of chondroitinase-ABC, TGF-β1, and collagen crosslinking agent lysyl oxidase to engineer functional neotissues for fibrocartilage repair. Biomaterials 35, 6787–6796 (2014).
Zhu, D., Tong, X., Trinh, P. & Yang, F. Mimicking cartilage tissue zonal organization by engineering tissue-scale gradient hydrogels as 3D cell niche. Tissue Eng. A 24, 1–10 (2018).
Steele, J. A. et al. Combinatorial scaffold morphologies for zonal articular cartilage engineering. Acta Biomater. 10, 2065–2075 (2014).
Zitnay, J. L. et al. Fabrication of dense anisotropic collagen scaffolds using biaxial compression. Acta Biomater. 65, 76–87 (2018).
Higashioka, M. M., Chen, J. A., Hu, J. C. & Athanasiou, K. A. Building an anisotropic meniscus with zonal variations. Tissue Eng. A 20, 294–302 (2014).
Darling, E. M. & Athanasiou, K. A. Rapid phenotypic changes in passaged articular chondrocyte subpopulations. J. Orthop. Res. 23, 425–432 (2005).
Huwe, L. W., Brown, W. E., Hu, J. C. & Athanasiou, K. A. Characterization of costal cartilage and its suitability as a cell source for articular cartilage tissue engineering. J. Tissue Eng. Regen. Med. 12, 1163–1176 (2018).
Kwon, H., O’Leary, S. A., Hu, J. C. & Athanasiou, K. A. Translating the application of transforming growth factor-β1, chondroitinase-ABC, and lysyl oxidase-like 2 for mechanically robust tissue-engineered human neocartilage. J. Tissue Eng. Regen. Med. 13, 283–294 (2019).
Murphy, M. K., Huey, D. J., Hu, J. C. & Athanasiou, K. A. TGF-β1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells. Stem Cells 33, 762–773 (2015).
Pelttari, K. et al. Adult human neural crest-derived cells for articular cartilage repair. Sci. Transl Med. 6, 251ra119 (2014).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02673905 (2018).
Bianchi, V. J., Weber, J. F., Waldman, S. D., Backstein, D. & Kandel, R. A. Formation of hyaline cartilage tissue by passaged human osteoarthritic chondrocytes. Tissue Eng. A 23, 156–165 (2017).
Kwon, H. et al. Tissue engineering potential of human dermis-isolated adult stem cells from multiple anatomical locations. PLoS One 12, e0182531 (2017).
Lavoie, J. F. et al. Skin-derived precursors differentiate into skeletogenic cell types and contribute to bone repair. Stem Cells Dev. 18, 893–906 (2009).
Fu, W. L., Zhou, C. Y. & Yu, J. K. A new source of mesenchymal stem cells for articular cartilage repair: MSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model. Am. J. Sports Med. 42, 592–601 (2014).
Chang, N. J. et al. Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits. Osteoarthritis Cartilage 21, 1613–1622 (2013).
Jiang, Y. et al. Human cartilage-derived progenitor cells from committed chondrocytes for efficient cartilage repair and regeneration. Stem Cells Transl Med. 5, 733–744 (2016).
Somoza, R. A., Welter, J. F., Correa, D. & Caplan, A. I. Chondrogenic differentiation of mesenchymal stem cells: challenges and unfulfilled expectations. Tissue Eng. B 20, 596–608 (2014).
Chen, S., Fu, P., Cong, R., Wu, H. & Pei, M. Strategies to minimize hypertrophy in cartilage engineering and regeneration. Genes Dis. 2, 76–95 (2015).
Kwon, H., Paschos, N. K., Hu, J. C. & Athanasiou, K. Articular cartilage tissue engineering: the role of signaling molecules. Cell. Mol. Life Sci. 73, 1173–1194 (2016).
Feng, Q. et al. Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy. Acta Biomater. 53, 329–342 (2017).
Amann, E., Wolff, P., Breel, E., van Griensven, M. & Balmayor, E. R. Hyaluronic acid facilitates chondrogenesis and matrix deposition of human adipose derived mesenchymal stem cells and human chondrocytes co-cultures. Acta Biomater. 52, 130–144 (2017).
Liu, Q. et al. Suppressing mesenchymal stem cell hypertrophy and endochondral ossification in 3D cartilage regeneration with nanofibrous poly(l-lactic acid) scaffold and matrilin-3. Acta Biomater. 76, 29–38 (2018).
Johnson, K. et al. A stem cell-based approach to cartilage repair. Science 336, 717–721 (2012).
Cai, G. et al. Recent advances in kartogenin for cartilage regeneration. J. Drug Target 27, 28–32 (2019).
Bian, L. et al. Influence of temporary chondroitinase ABC-induced glycosaminoglycan suppression on maturation of tissue-engineered cartilage. Tissue Eng. A 15, 2065–2072 (2009).
Natoli, R. M., Revell, C. M. & Athanasiou, K. A. Chondroitinase ABC treatment results in greater tensile properties of self-assembled tissue-engineered articular cartilage. Tissue Eng. A 15, 3119–3128 (2009).
Makris, E. A., Responte, D. J., Paschos, N. K., Hu, J. C. & Athanasiou, K. A. Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking. Proc. Natl Acad. Sci. USA 111, E4832–E4841 (2014).
Makris, E. A., Hu, J. C. & Athanasiou, K. A. Hypoxia-induced collagen crosslinking as a mechanism for enhancing mechanical properties of engineered articular cartilage. Osteoarthritis Cartilage 21, 634–641 (2013).
Athanasiou, K. A., Darling, E. M., Hu, J. C., DuRaine, G. D. & Reddi, A. H. Articular Cartilage 2nd edn Ch. 1 18–25 (Taylor & Francis, 2016).
Huwe, L. W., Sullan, G. K., Hu, J. C. & Athanasiou, K. A. Using costal chondrocytes to engineer articular cartilage with applications of passive axial compression and bioactive stimuli. Tissue Eng. A 24, 516–526 (2018).
Meinert, C., Schrobback, K., Hutmacher, D. W. & Klein, T. J. A novel bioreactor system for biaxial mechanical loading enhances the properties of tissue-engineered human cartilage. Sci. Rep. 7, 16997 (2017).
Son, M. S. & Levenston, M. E. Quantitative tracking of passage and 3D culture effects on chondrocyte and fibrochondrocyte gene expression. J. Tissue Eng. Regen. Med. 11, 1185–1194 (2017).
Zellner, J. et al. Role of mesenchymal stem cells in tissue engineering of meniscus. J. Biomed. Mater. Res. A 94, 1150–1161 (2010).
Moriguchi, Y. et al. Repair of meniscal lesions using a scaffold-free tissue-engineered construct derived from allogenic synovial MSCs in a miniature swine model. Biomaterials 34, 2185–2193 (2013).
Sasaki, H. et al. In vitro repair of meniscal radial tear with hydrogels seeded with adipose stem cells and TGF-β3. Am. J. Sports Med. 46, 2402–2413 (2018).
Koh, R. H., Jin, Y. J., Kang, B. J. & Hwang, N. S. Chondrogenically primed tonsil-derived mesenchymal stem cells encapsulated in riboflavin-induced photocrosslinking collagen-hyaluronic acid hydrogel for meniscus tissue repairs. Acta Biomater. 53, 318–328 (2017).
Xie, X. et al. A co-culture system of rat synovial stem cells and meniscus cells promotes cell proliferation and differentiation as compared to mono-culture. Sci. Rep. 8, 7693 (2018).
Hadidi, P. et al. Tendon and ligament as novel cell sources for engineering the knee meniscus. Osteoarthritis Cartilage 24, 2126–2134 (2016).
Pangborn, C. A. & Athanasiou, K. A. Growth factors and fibrochondrocytes in scaffolds. J. Orthop. Res. 23, 1184–1190 (2005).
Bonnevie, E. D., Puetzer, J. L. & Bonassar, L. J. Enhanced boundary lubrication properties of engineered menisci by lubricin localization with insulin-like growth factor I treatment. J. Biomech. 47, 2183–2188 (2014).
Lee, C. H. et al. Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep. Sci. Transl Med. 6, 266ra171 (2014).
Liang, Y. et al. Plasticity of human meniscus fibrochondrocytes: a study on effects of mitotic divisions and oxygen tension. Sci. Rep. 7, 12148 (2017).
Croutze, R., Jomha, N., Uludag, H. & Adesida, A. Matrix forming characteristics of inner and outer human meniscus cells on 3D collagen scaffolds under normal and low oxygen tensions. BMC Musculoskelet. Disord. 14, 353 (2013).
Huey, D. J. & Athanasiou, K. A. Tension-compression loading with chemical stimulation results in additive increases to functional properties of anatomic meniscal constructs. PLoS One 6, e27857 (2011).
Zellner, J. et al. Dynamic hydrostatic pressure enhances differentially the chondrogenesis of meniscal cells from the inner and outer zone. J. Biomech. 48, 1479–1484 (2015).
Puetzer, J. L. & Bonassar, L. J. Physiologically distributed loading patterns drive the formation of zonally organized collagen structures in tissue-engineered meniscus. Tissue Eng. A 22, 907–916 (2016).
MacBarb, R. F., Chen, A. L., Hu, J. C. & Athanasiou, K. A. Engineering functional anisotropy in fibrocartilage neotissues. Biomaterials 34, 9980–9989 (2013).
Huang, B. J., Hu, J. C. & Athanasiou, K. A. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage. Biomaterials 98, 1–22 (2016).
McCormick, F. et al. Treatment of focal cartilage defects with a juvenile allogeneic 3-dimensional articular cartilage graft. Oper. Tech. Sports Med. 21, 95–99 (2013).
Park, Y. B., Ha, C. W., Lee, C. H., Yoon, Y. C. & Park, Y. G. Cartilage regeneration in osteoarthritic patients by a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: results from a clinical trial for safety and proof-of-concept with 7 years of extended follow-up. Stem Cells Transl Med. 6, 613–621 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01733186 (2018).
Rhee, C., Amar, E., Glazebrook, M., Coday, C. & Wong, I. H. Safety profile and short-term outcomes of BST-CarGel as an adjunct to microfracture for the treatment of chondral lesions of the hip. Orthop. J. Sports Med. 6, 2325967118789871 (2018).
Tahoun, M. et al. Results of arthroscopic treatment of chondral delamination in femoroacetabular impingement with bone marrow stimulation and BST-CarGel((R)). SICOT J. 3, 51 (2017).
Thier, S., Weiss, C. & Fickert, S. Arthroscopic autologous chondrocyte implantation in the hip for the treatment of full-thickness cartilage defects—a case series of 29 patients and review of the literature. SICOT J. 3, 72 (2017).
Whitehouse, M. R. et al. Repair of torn avascular meniscal cartilage using undifferentiated autologous mesenchymal stem cells: from in vitro optimization to a first-in-human study. Stem Cells Transl Med. 6, 1237–1248 (2017).
Vangsness, C. T. Jr. et al. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J. Bone Joint Surg. 96, 90–98 (2014).
Murphy, M. K., Masters, T. E., Hu, J. C. & Athanasiou, K. A. Engineering a fibrocartilage spectrum through modulation of aggregate redifferentiation. Cell Transplant. 24, 235–245 (2015).
Martin, F., Lehmann, M., Sack, U. & Anderer, U. Featured article: In vitro development of personalized cartilage microtissues uncovers an individualized differentiation capacity of human chondrocytes. Exp. Biol. Med. 242, 1746–1756 (2017).
Vapniarsky, N. et al. Tissue engineering toward temporomandibular joint disc regeneration. Sci. Transl Med. 10, eaaq1802 (2018).
US Food & Drug Administration. Guidance for industry: eligibility determination for donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps). FDA.gov https://www.fda.gov/media/73072/download (2015).
Arvayo, A. L., Wong, I. J., Dragoo, J. L. & Levenston, M. E. Enhancing integration of articular cartilage grafts via photochemical bonding. J. Orthop. Res. 36, 2406–2415 (2018).
Athens, A. A., Makris, E. A. & Hu, J. C. Induced collagen cross-links enhance cartilage integration. PLoS One 8, e60719 (2013).
Utomo, L., van Osch, G. J., Bayon, Y., Verhaar, J. A. & Bastiaansen-Jenniskens, Y. M. Guiding synovial inflammation by macrophage phenotype modulation: an in vitro study towards a therapy for osteoarthritis. Osteoarthritis Cartilage 24, 1629–1638 (2016).
Lai, J. H. et al. Interaction between osteoarthritic chondrocytes and adipose-derived stem cells is dependent on cell distribution in three-dimension and transforming growth factor-β3 induction. Tissue Eng. A 21, 992–1002 (2015).
Elder, B. D., Eleswarapu, S. V. & Athanasiou, K. A. Extraction techniques for the decellularization of tissue engineered articular cartilage constructs. Biomaterials 30, 3749–3756 (2009).
Cissell, D. D., Hu, J. C., Griffiths, L. G. & Athanasiou, K. A. Antigen removal for the production of biomechanically functional, xenogeneic tissue grafts. J. Biomech. 47, 1987–1996 (2014).
McNickle, A. G., Wang, V. M., Shewman, E. F., Cole, B. J. & Williams, J. M. Performance of a sterile meniscal allograft in an ovine model. Clin. Orthop. Relat. Res. 467, 1868–1876 (2009).
US Food & Drug Administration. Expedited programs for regenerative medicine therapies for serious conditions: guidance for industry. FDA.gov https://www.fda.gov/media/120267/download (2017).
Nehrer, S., Chiari, C., Domayer, S., Barkay, H. & Yayon, A. Results of chondrocyte implantation with a fibrin-hyaluronan matrix: a preliminary study. Clin. Orthop. Relat. Res. 466, 1849–1855 (2008).
Domayer, S. E. et al. T2 mapping and dGEMRIC after autologous chondrocyte implantation with a fibrin-based scaffold in the knee: preliminary results. Eur. J. Radiol. 73, 636–642 (2010).
Fontana, A., Bistolfi, A., Crova, M., Rosso, F. & Massazza, G. Arthroscopic treatment of hip chondral defects: autologous chondrocyte transplantation versus simple debridement—a pilot study. Arthroscopy 28, 322–329 (2012).
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).
Kreuz, P. C., Muller, 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).
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).
Schneider, U. et al. A prospective multicenter study on the outcome of type I collagen hydrogel-based autologous chondrocyte implantation (CaReS) for the repair of articular cartilage defects in the knee. Am. J. Sports Med. 39, 2558–2565 (2011).
Cole, B. J. et al. Outcomes after a single-stage procedure for cell-based cartilage repair: a prospective clinical safety trial with 2-year follow-up. Am. J. Sports Med. 39, 1170–1179 (2011).
Selmi, T. A. et al. Autologous chondrocyte implantation in a novel alginate-agarose hydrogel: outcome at two years. J. Bone Joint Surg. Br. 90, 597–604 (2008).
Clave, A. et al. Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial. J. Orthop. Res. 34, 658–665 (2016).
Fickert, S. et al. One-year clinical and radiological results of a prospective, investigator-initiated trial examining a novel, purely autologous 3-dimensional autologous chondrocyte transplantation product in the knee. Cartilage 3, 27–42 (2012).
Meyer, U., Meyer, Th., Handschel, J. & Wiesmann, H. P. (eds) Fundamentals of Tissue Engineering and Regenerative Medicine (Springer, 2009).
Gobbi, A. et al. One-step surgery with multipotent stem cells and hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years. Knee Surg. Sports Traumatol. Arthrosc. 25, 2494–2501 (2017).
Marcacci, M. et al. Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin. Orthopaed. Related Res. 435, 96–105 (2005).
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).
Tognana, E., Borrione, A., De Luca, C. & Pavesio, A. Hyalograft C: hyaluronan-based scaffolds in tissue-engineered cartilage. Cells Tissues Organs 186, 97–103 (2007).
Brittberg, M. in Techniques in Cartilage Repair Surgery Ch. 19 (eds Shetty, A. A. et al.) 227–235 (Springer, 2014).
Hendriks, J. et al. First clinical experience with INSTRUCT—a single surgery, autologous cell based technology for cartilage repair [poster]. CellCoTec http://www.cellcotec.com/wp-content/uploads/2017/11/P187-first-clinical-experience-with-INSTRUCT-final2.pdf (2013).
Zak, L. et al. Results 2 years after matrix-associated autologous chondrocyte transplantation using the Novocart 3D scaffold: an analysis of clinical and radiological data. Am. J. Sports Med. 42, 1618–1627 (2014).
Crawford, D. C., DeBerardino, T. M. & Williams, R. J. 3rd NeoCart, an autologous cartilage tissue implant, compared with microfracture for treatment of distal femoral cartilage lesions: an FDA phase-II prospective, randomized clinical trial after two years. J. Bone Joint Surg. Am. 94, 979–989 (2012).
Crawford, D. C. et al. An autologous cartilage tissue implant NeoCart for treatment of grade III chondral injury to the distal femur: prospective clinical safety trial at 2 years. Am. J. Sports Med. 37, 1334–1343 (2009).
Mizuno, S., Kusanagi, A., Tarrant, L. J. B., Tokuno, T. & Smith, R. L. Systems for cartilage repair. US Patent 20130273121A1 (2013).
Mumme, M. et al. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. Lancet 388, 1985–1994 (2016).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00729716 (2012).
European Medicines Agency. EU Clinical Trials Register https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-003594-28/DE (2011).
German Institute of Medical Documentation and Information. German Clinical Trials Register http://www.drks.de/DRKS00010658 (2016).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02981355 (2018).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02540200 (2016).
Shive, M. S. et al. BST-CarGel(R) treatment maintains cartilage repair superiority over microfracture at 5 years in a multicenter randomized controlled trial. Cartilage 6, 62–72 (2015).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01498029 (2012).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00881023 (2016).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00945399 (2015).
European Medicines Agency. EU Clinical Trials Register https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-003481-18/BE (2008).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01626677 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01041001 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01222559 (2018).
Becher, C. et al. Safety of three different product doses in autologous chondrocyte implantation: results of a prospective, randomised, controlled trial. J. Orthop. Surg. Res. 12, 71 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02659215 (2018).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03219307 (2019).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02348697 (2019).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01957722 (2019).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01656902 (2018).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03319797 (2019).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02941120 (2019).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02179346 (2019).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01066702 (2019).
Anderson, D. E. et al. Magnetic resonance imaging characterization and clinical outcomes after neocart surgical therapy as a primary reparative treatment for knee cartilage injuries. Am. J. Sports Med. 45, 875–883 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01400607 (2017).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00702741 (2014).
European Medicines Agency. EU Clinical Trials Register https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-024162-22/GB (2011).
Acknowledgements
The work of the authors was supported by the National Institutes of Health (grants R01AR067821 and R01AR071457 to K.A.A.), and by funds provided by the Henry Samueli Chair in Engineering.
Peer review information
Nature Reviews Rheumatology thanks H. Madry, E. Kon and D. J. Kelly for their contribution to the peer review of this work.
Author information
Authors and Affiliations
Contributions
H.K., W.E.B., C.A.L., D.W., N.P. and J.C.H. researched data for this article. All authors provided substantial contributions to the discussion of content, wrote the article and reviewed and/or edited the article before submission. H.K. and W.E.B. contributed equally to this article.
Corresponding author
Ethics declarations
Competing interests
W.E.B. declares she is the Director of Outreach and a social media contributor for Science Cheerleaders, Incorporated. C.A.L. declares she is on the advisory board of Vericel. N.P. declares he is an associate editor of the Arthroscopy Journal. K.A.A. declares he is on the scientific advisory board of Histogenics. K.A.A., J.C.H., H.K. and W.E.B. declare they are listed as co-authors of submitted US patent applications (16/136,894 and 16/137,120). D.W. declares no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Glossary
- Debridement
-
The removal of damaged tissue and/or torn fragments from a defect.
- Hoop stresses
-
Compressive forces experienced by the meniscus in the circumferential direction.
- Rasping
-
Mechanical scraping to expose fresh and/or bleeding tissue.
- Radial trephination
-
Puncturing small holes into the joint lining and/or synovium and into the tissue to stimulate healing.
- Bone plugs
-
Created or fashioned bone cylinders containing the enthesis of the meniscal roots.
- Common bone bridge
-
Excised bone containing and preserving the anatomic relationship between the anterior and posterior meniscal horns (also known as ‘slot’).
- Hemi-plateau
-
Half of the tibial plateau, containing the articular surface, subchondral bone and meniscus with root attachments.
- Lysholm score
-
A scoring system used to measure changes in limping, support, locking, instability, pain, swelling, stair climbing and squatting (originally developed to evaluate outcomes of knee ligament surgery).
- Stress shielding
-
Protection of tissue from normal mechanical stresses by the presence of a much stiffer implant, often resulting in tissue loss.
- Self-assembling process
-
A scaffold-free technology that produces tissues that demonstrate spontaneous organization without external forces via the minimization of free energy through cell-to-cell interactions.
- Anisotropy
-
Having directionally dependent properties.
- International Knee Documentation Committee (IKDC) score
-
A scoring system used to measure symptoms, sports and daily activities, current knee function and function before injury.
- International Cartilage Repair Society (ICRS)-Cartilage Repair Assessment System
-
A tool used to macroscopically evaluate the quality of cartilage repair tissue.
- International Hip Outcome Tool
-
A tool used to measure symptoms, functional limitation, work-related concerns, sports and recreational activities, and social, emotional and lifestyle concerns using a visual analogue scale.
- Tegner–Lysholm score
-
A patient-reported score of the effect of knee pain and stability on daily life.
- Range of motion (ROM) score
-
A measurement of the range of flexion and extension of a joint.
- Tribological properties
-
Functional properties relating to friction and lubrication of tissues.
Rights and permissions
About this article
Cite this article
Kwon, H., Brown, W.E., Lee, C.A. et al. Surgical and tissue engineering strategies for articular cartilage and meniscus repair. Nat Rev Rheumatol 15, 550–570 (2019). https://doi.org/10.1038/s41584-019-0255-1
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41584-019-0255-1
This article is cited by
-
Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity
Journal of Nanobiotechnology (2024)
-
Silk fibroin hydrogel adhesive enables sealed-tight reconstruction of meniscus tears
Nature Communications (2024)
-
Biomimetic ECM-Based Hybrid Scaffold for Cartilage Tissue Engineering Applications
Journal of Polymers and the Environment (2024)
-
Low-intensity pulsed ultrasound promotes mesenchymal stem cell transplantation-based articular cartilage regeneration via inhibiting the TNF signaling pathway
Stem Cell Research & Therapy (2023)
-
Effect of autogenous osteochondral mosaicplasty on the balance control of patients with cartilage defects of the knee: a pilot study
Journal of Orthopaedic Surgery and Research (2023)