As a contour-supporting material, the cartilage has a significant application value in plastic surgery. Since the development of hydrogel scaffolds with sufficient biomechanical strength and high biocompatibility, cell-laden hydrogels have been widely studied for application in cartilage bioengineering. This systematic review summarizes the latest research on engineered cartilage constructed using cell-laden hydrogel scaffolds in plastic surgery.
A systematic review was performed by searching the PubMed and Web of Science databases using selected keywords and Medical Subject Headings search terms.
Forty-two studies were identified based on the search criteria. After full-text screening for inclusion and exclusion criteria, 18 studies were included. Data collected from each study included culturing form, seed cell types and sources, concentration of cells and gels, scaffold materials and bio-printing structures, and biomechanical properties of cartilage constructs. These cell-laden hydrogel scaffolds were reported to show some feasibility of cartilage engineering, including better cell proliferation, enhanced deposition of glycosaminoglycans and collagen type II in the extracellular matrix, and better biomechanical properties close to the natural state.
Cell-laden hydrogels have been widely used in cartilage bioengineering research. Through 3-dimensional (3D) printing, the cell-laden hydrogel can form a bionic contour structure. Extracellular matrix expression was observed in vivo and in vitro, and the elastic modulus was reported to be similar to that of natural cartilage. The future direction of cartilage tissue engineering in plastic surgery involves the use of novel hydrogel materials and more advanced 3D printing technology combined with biochemistry and biomechanical stimulation.
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Wiggenhauser PS, Schantz JT, Rotter N. Cartilage engineering in reconstructive surgery: auricular, nasal and tracheal engineering from a surgical perspective. Regen Med. 2017;12:303–14.
Daniel RK. Rhinoplasty: dorsal grafts and the designer dorsum. Clinics Plast Surg. 2010;37:293–300.
Zhou F, Hong Y, Zhang X, Yang L, Li J, Jiang D, et al. Tough hydrogel with enhanced tissue integration and in situ forming capability for osteochondral defect repair. Appl Mater Today. 2018;13:32–44.
Yang J, Zhang YS, Yue K, Khademhosseini A. Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta Biomater. 2017;57:1–25.
Tanaka Y, Yamaoka H, Nishizawa S, Nagata S, Ogasawara T, Asawa Y, et al. The optimization of porous polymeric scaffolds for chondrocyte/atelocollagen based tissue-engineered cartilage. Biomaterials. 2010;31:4506–16.
Bichara DA, Zhao X, Hwang NS, Bodugoz-Senturk H, Yaremchuk MJ, Randolph MA, et al. Porous poly(vinyl alcohol)-alginate gel hybrid construct for neocartilage formation using human nasoseptal cells. J Surg Res. 2010;163:331–6.
Reiffel AJ, Kafka C, Hernandez KA, Popa S, Perez JL, Zhou S, et al. High-fidelity tissue engineering of patient-specific auricles for reconstruction of pediatric microtia and other auricular deformities. PloS One. 2013;8:e56506.
Chen CH, Shyu VB, Chen JP, Lee MY. Selective laser sintered poly-epsilon-caprolactone scaffold hybridized with collagen hydrogel for cartilage tissue engineering. Biofabrication. 2014;6:015004.
Cohen BP, Hooper RC, Puetzer JL, Nordberg R, Asanbe O, Hernandez KA, et al. Long-term morphological and microarchitectural stability of tissue-engineered, patient-specific auricles in vivo. Tissue Eng Part A. 2016;22:461–8.
Zopf DA, Flanagan CL, Mitsak AG, Brennan JR, Hollister SJ. Pore architecture effects on chondrogenic potential of patient-specific 3-dimensionally printed porous tissue bioscaffolds for auricular tissue engineering. Int J Pediatr Otorhinolaryngol. 2018;114:170–4.
Visscher DO, Gleadall A, Buskermolen JK, Burla F, Segal J, Koenderink GH, et al. Design and fabrication of a hybrid alginate hydrogel/poly(epsilon-caprolactone) mold for auricular cartilage reconstruction. J Biomed Mater Res B Appl Biomater. 2019;107:1711–21.
Ruiz-Cantu L, Gleadall A, Faris C, Segal J, Shakesheff K, Yang J. Multi-material 3D bioprinting of porous constructs for cartilage regeneration. Mater Sci Eng C Mater Biol Appl. 2020;109:110578.
Xu Y, Xu Y, Bi B, Hou M, Yao L, Du Q, et al. A moldable thermosensitive hydroxypropyl chitin hydrogel for 3D cartilage regeneration in vitro and in vivo. Acta Biomater. 2020;108:87–96.
Visscher DO, Lee H, van Zuijlen PPM, Helder MN, Atala A, Yoo JJ, et al. A photo-crosslinkable cartilage-derived extracellular matrix bioink for auricular cartilage tissue engineering. Acta Biomater. 2021;121:193–203.
Otto IA, Levato R, Webb WR, Khan IM, Breugem CC, Malda J. Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture. Eur Cell Mater. 2018;35:132–50.
Yi HG, Choi YJ, Jung JW, et al. Three-dimensional printing of a patient-specific engineered nasal cartilage for augmentative rhinoplasty. J Tissue Eng. 2019;10:2041731418824797.
Visscher DO, Bos EJ, Peeters M, Kuzmin NV, Groot ML, Helder MN, et al. Cartilage tissue engineering: preventing tissue scaffold contraction using a 3D-printed polymeric cage. Tissue Eng Part C Methods. 2016;22:573–84.
Morrison KA, Cohen BP, Asanbe O, Dong X, Harper A, Bonassar LJ, et al. Optimizing cell sourcing for clinical translation of tissue engineered ears. Biofabrication. 2016;9:015004.
Möller T, Amoroso M, Hägg D, Brantsing C, Rotter N, Apelgren P, et al. In vivo chondrogenesis in 3D bioprinted human cell-laden hydrogel constructs. Plast Reconstr Surg Glob Open. 2017;5:e1227.
Apelgren P, Amoroso M, Lindahl A, et al. Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo. PloS One. 2017;12:e0189428.
Chang CS, Yang CY, Hsiao HY, Chen L, Chu IM, Cheng MH, et al. Cultivation of auricular chondrocytes in poly(ethylene glycol)/poly(epsilon-caprolactone) hydrogel for tracheal cartilage tissue engineering in a rabbit model. Eur Cell Mater. 2018;35:350–64.
Morrison RJ, Nasser HB, Kashlan KN, Zopf DA, Milner DJ, Flanangan CL, et al. Co-culture of adipose-derived stem cells and chondrocytes on three-dimensionally printed bioscaffolds for craniofacial cartilage engineering. Laryngoscope. 2018;128:E251-7.
Li D, An Y, Yang X. An overview of asian rhinoplasty. Ann Plast Surg. 2016;77:S22-4.
Idone F. Diced cartilage grafts wrapped in rectus abdominis fascia for nasal dorsum augmentation. Plast Reconstr Surg. 2016;138:762e.
Storck K, Staudenmaier R, Buchberger M, Strenger T, Kreutzer K, von Bomhard A, et al. Total reconstruction of the auricle: our experiences on indications and recent techniques. Biomed Res Int. 2014;2014:373286.
Nagata S. A new method of total reconstruction of the auricle for microtia. Plast Reconstr Surg. 1993;92:187–201.
Liao J, Chen Y, Chen J, He B, Qian L, Xu J, et al. Auricle shaping using 3D printing and autologous diced cartilage. Laryngoscope. 2019;129:2467–74.
Eke G, Mangir N, Hasirci N, MacNeil S, Hasirci V. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. Biomaterials. 2017;129:188–98.
Lam T, Dehne T, Krüger JP, Hondke S, Endres M, Thomas A, et al. Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue-engineered cartilage. J Biomed Mater Res B Appl Biomater. 2019;107:2649–57.
Nemeth CL, Janebodin K, Yuan AE, Dennis JE, Reyes M, Kim DH. Enhanced chondrogenic differentiation of dental pulp stem cells using nanopatterned PEG-GelMA-HA hydrogels. Tissue Eng Part A. 2014;20:2817–29.
Boere KW, Visser J, Seyednejad H, Rahimian S, Gawlitta D, van Steenbergen MJ, et al. Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs. Acta Biomater. 2014;10:2602–11.
Shi W, Sun M, Hu X, Ren B, Cheng J, Li C, et al. Structurally and functionally optimized silk-fibroin-gelatin scaffold using 3d printing to repair cartilage injury in vitro and in vivo. Adv Mater. 2017. https://doi.org/10.1002/adma.201701089.
Levett PA, Melchels FP, Schrobback K, Hutmacher DW, Malda J, Klein TJ. A biomimetic extracellular matrix for cartilage tissue engineering centered on photocurable gelatin, hyaluronic acid and chondroitin sulfate. Acta Biomater. 2014;10:214–23.
Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254–71.
Ma Q, Liao J, Cai X. Different sources of stem cells and their application in cartilage tissue engineering. Curr Stem Cell Res Ther. 2018;13:568–75.
You Q, Liu Z, Zhang J, Shen M, Li Y, Jin Y, et al. Human amniotic mesenchymal stem cell sheets encapsulating cartilage particles facilitate repair of rabbit osteochondral defects. Am J Sports Med. 2020;48:599–611.
Veronesi F, Maglio M, Tschon M, Aldini NN, Fini M. Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies. J Biomed Mater Res A. 2014;102:2448–66.
Bexkens R, Ogink PT, Doornberg JN, Kerkhoffs GMMJ, Eygendaal D, Oh LS, et al. Donor-site morbidity after osteochondral autologous transplantation for osteochondritis dissecans of the capitellum: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2017;25:2237–46.
Hurley ET, Yasui Y, Gianakos AL, Seow D, Shimozono Y, Kerkhoffs GMMJ, et al. Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2018;26:3499–507.
Scioli MG, Bielli A, Gentile P, Cervelli V, Orlandi A. Combined treatment with platelet-rich plasma and insulin favours chondrogenic and osteogenic differentiation of human adipose-derived stem cells in three-dimensional collagen scaffolds. J Tissue Eng Regen Med. 2017;11:2398–410.
Yang Q, Teng BH, Wang LN, Li K, Xu C, Ma XL, et al. Silk fibroin/cartilage extracellular matrix scaffolds with sequential delivery of TGF-beta 3 for chondrogenic differentiation of adipose-derived stem cells. Int J Nanomedicine. 2017;12:6721–33.
Cho H, Kim J, Kim S, Jung YC, Wang Y, Kang BJ, et al. Dual delivery of stem cells and insulin-like growth factor-1 in coacervate-embedded composite hydrogels for enhanced cartilage regeneration in osteochondral defects. J Control Release. 2020;327:284–95.
Deng ZH, Li YS, Gao X, Lei GH, Huard J. Bone morphogenetic proteins for articular cartilage regeneration. Osteoarthritis Cartilage. 2018;26:1153–61.
Chen Y, Ma M, Teng Y, Cao H, Yang Y, Wang Y, et al. Efficient manufacturing of tissue engineered cartilage in vitro by a multiplexed 3D cultured method. J Mater Chem B. 2020;8:2082–95.
De Moor L, Fernandez S, Vercruysse C, Tytgat L, Asadian M, De Geyter N, et al. Hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids. Front Bioeng Biotechnol. 2020;8:484.
Vainieri ML, Lolli A, Kops N, D'Atri D, Eglin D, Yayon A, et al. Evaluation of biomimetic hyaluronic-based hydrogels with enhanced endogenous cell recruitment and cartilage matrix formation. Acta Biomater. 2020;101:293–303.
Hao J, Zhang Y, Jing D, Shen Y, Tang G, Huang S, et al. Mechanobiology of mesenchymal stem cells: perspective into mechanical induction of MSC fate. Acta Biomater. 2015;20:1–9.
Huebsch N, Arany PR, Mao AS, Shvartsman D, Ali OA, Bencherif SA, et al. Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater. 2010;9:518–26.
Khetan S, Guvendiren M, Legant WR, Cohen DM, Chen CS, Burdick JA. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat Mater. 2013;12:458–65.
Sen B, Xie Z, Case N, Ma M, Rubin C, Rubin J. Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal. Endocrinology. 2008;149:6065–75.
Lee J, Abdeen AA, Zhang D, Kilian KA. Directing stem cell fate on hydrogel substrates by controlling cell geometry, matrix mechanics and adhesion ligand composition. Biomaterials. 2013;34:8140–8.
Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater. 2007;6:997–1003.
Liao S, Nguyen LT, Ngiam M, Wang C, Cheng Z, Chan CK, et al. Biomimetic nanocomposites to control osteogenic differentiation of human mesenchymal stem cells. Adv Healthc Mater. 2014;3:737–51.
Kilian KA, Bugarija B, Lahn BT, Mrksich M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Nat Acad Sci U S A. 2010;107:4872–7.
Zhang ZZ, Chen YR, Wang SJ, Zhao F, Wang XG, Yang F, et al. Orchestrated biomechanical structural and biochemical stimuli for engineering anisotropic meniscus. Sci Transl Med. 2019;11:eaao0750.
This article was funded by China Postdoctoral Science Foundation with the number of 2020M670001ZX.
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Wang, G., Zhang, X., Bu, X. et al. The Application of Cartilage Tissue Engineering with Cell-Laden Hydrogel in Plastic Surgery: A Systematic Review. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00394-5
- 3D bioprinting
- Tissue engineering
- Cell-laden hydrogel
- Plastic surgery