6964Accesses
328Citations
3Altmetric
Abstract
There has been a consistent increase in the mean life expectancy of the population of the developed world over the past century. Healthy life expectancy, however, has not increased concurrently. As a result we are living a larger proportion of our lives in poor health and there is a growing demand for the replacement of diseased and damaged tissues. While traditionally tissue grafts have functioned well for this purpose, the demand for tissue grafts now exceeds the supply. For this reason, research in regenerative medicine is rapidly expanding to cope with this new demand. There is now a trend towards supplying cells with a material in order to expedite the tissue healing process. Hydrogel encapsulation provides cells with a three dimensional environment similar to that experienced in vivo and therefore may allow the maintenance of normal cellular function in order to produce tissues similar to those found in the body. In this review we discuss biopolymeric gels that have been used for the encapsulation of mammalian cells for tissue engineering applications as well as a brief overview of cell encapsulation for therapeutic protein production. This review focuses on agarose, alginate, collagen, fibrin, hyaluronic acid and gelatin since they are widely used for cell encapsulation. The literature on the regeneration of cartilage, bone, ligament, tendon, skin, blood vessels and neural tissues using these materials has been summarised.
This is a preview of subscription content,log in via an institution to check access.
Access this article
Subscribe and save
- Get 10 units per month
- Download Article/Chapter or eBook
- 1 Unit = 1 Article or 1 Chapter
- Cancel anytime
Buy Now
Price includes VAT (Japan)
Instant access to the full article PDF.
Similar content being viewed by others
References
Abbott A (2003) Biology’s new dimension. Nature 424:870–872
Alaminos M, Sanchez-Quevdo MD, Munoz-Avila JI, Serrano D, Medialdea S, Carreras I, Campos A (2006) Construction of a complete rabbit cornea substitute using a fibrin-agarose scaffold. Investig Ophthalmol Vis Sci 47:3311–3317
Augst AD, Kong HJ, Mooney DJ (2006) Alginate hydrogels as biomaterials. Macromol Biosci 6:623–633
Bach AD, Bannasch H, Galla TJ, Bittner KM, Stark GB (2001) Fibrin glue as matrix for cultured autologous urothelial cells in urethral reconstruction. Tissue Eng 7:45–53
Bannasch H, Horch RE, Tanczos E, Stark GB (2000) Treatment of chronic wounds with cultivated autologous keratinocytes as suspension in fibrin glue. Zentralbl Chir 125:79–81
Bannasch H, Unterberg T, Fohn M, Weyand B, Horch RE, Stark GB (2008) Cultured keratinocytes in fibrin with decellularised dermis close porcine full-thickness wounds in a single step. Burns 34:1015–1021
Bellamkonda R, Ranieri JP, Bouche N, Aebischer P (1995) Hydrogel-based 3-dimensional matrix for neural cells. J Biomed Mater Res 29:663–671
Berendse M, Grounds MD, Lloyd CA (2003) Myoblast structure affects subsequent skeletal myotube morphology and sarcomere assembly. Exp Cell Res 291:435–450
Birla RK, Borschel GH, Dennis RG, Brown DL (2005) Myocardial engineering in vivo: formation and characterization of contractile, vascularized three-dimensional cardiac tissue. Tissue Eng 11:803–813
Bitar M, Salih V, Brown RA, Nazhat SN (2007) Effect of multiple unconfined compressions on cellular dense collagen scaffolds for bone tissue engineering. J Mater Sci Mater Med 18:237–244
Bokharia MA, Akaya G, Zhang S, Birch MA (2005) The enhancement of osteoblast growth and differentiation in vitro on a peptide hydrogel—polyHIPE polymer hybrid material. Biomaterials 26:5198–5208
Brown LF, Lanir N, Mcdonagh J, Tognazzi K, Dvorak AM, Dvorak HF (1993) Fibroblast migration in fibrin gel matrices. Am J Pathol 142:273–283
Brown RA, Wiseman M, Chuo CB, Cheema U, Nazhat SN (2005) Ultrarapid engineering of biomimetic materials and tissues: fabrication of nano- and microstructures by plastic compression. Adv Funct Mater 15:1762–1770
Bruns H, Kneser U, Holzhuter S, Roth B, Kluth J, Kaufmann PM, Kluth D, Fiegel HC (2005) Injectable liver: a novel approach using fibrin gel as a matrix for culture and intrahepatic transplantation of hepatocytes. Tissue Eng 11:1718–1726
Calafiore R, Basta G, Luca G, Lemmi A, Racanicchi L, Mancuso F, Montanucci MP, Brunetti P (2006) Standard technical procedures for microencapsulation of human islets for graft into nonimmunosuppressed patients with type 1 diabetes mellitus. Transplant Proc 38:1156–1157
Carvalho HF, Felisbino SL, Covizi DZ, la Colleta HHM, Gomes L (2000) Structure and proteoglycan composition of specialized regions of the elastic tendon of the chicken wing. Cell Tissue Res 300:435–446
Catelas I, Sese N, Wu BM, Dunn JCY, Helgerson S, Tawil B (2006) Human mesenchymal stem cell proliferation and osteogenic differentiation in fibrin gels in vitro. Tissue Eng 12:2385–2396
Chan BP, Leong KW (2008) Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J 17:S467–S479
Chang PL, Hortelano G, Tse M, Awrey DE (1994) Growth of recombinant fibroblasts in alginate microcapsules. Biotechnol Bioeng 43:925–933
Cheema U, Yang SY, Mudera V, Goldspink GG, Brown RA (2003) 3-D in vitro model of early skeletal muscle development. Cell Motil Cytoskeleton 54:226–236
Cheema U, Nazhat SN, Alp B, Foroughi F, Anandagoda N, Mudera V, Brown RA (2007) Fabricating tissues: analysis of farming versus engineering strategies. Biotechnol Bioproc Eng 12:9–14
Choi BH, Woo JI, Min BH, Park SR (2006) Low-intensity ultrasound stimulates the viability and matrix gene expression of human articular chondrocytes in alginate bead culture. J Biomed Mater Res 79A:858–864
Choi NW, Cabodi M, Held B, Gleghorn JP, Bonassar LJ, Stroock AD (2007) Microfluidic scaffolds for tissue engineering. Nat Mater 6:908–915
Chun J, Tuan TL, Han B, Vangsness CT, Nimni ME (2003) Cultures of ligament fibroblasts in fibrin matrix gel. Connect Tissue Res 44:81–87
Chung C, Erickson IE, Mauck RL, Burdick JA (2008) Differential behavior of auricular and articular chondrocytes in hyaluronic acid hydrogels. Tissue Eng 14A:1121–1131
Cleary EG, Sandberg LB, Jackson DS (1967) Changes in chemical composition during development of bovine nuchal ligament. J Cell Biol 33:469–479
Cox S, Cole M, Tawil B (2004) Behavior of human dermal fibroblasts in three-dimensional fibrin clots: dependence on fibrinogen and thrombin concentration. Tissue Eng 10:942–954
Crimmins EM, Saito Y (2001) Trends in healthy life expectancy in the United States, 1970–1990: gender, racial, and educational differences. Soc Sci Med 52:1629–1641
Dunn JCY, Yarmush ML, Koebe HG, Tompkins RG (1989) Hepatocyte function and extracellular-matrix geometry—long-term culture in a sandwich configuration. Faseb J 3(2):174–177
Eyrich D, Brandl F, Appel B, Wiese H, Maier G, Wenzel M, Staudenmaier R, Goepferich A, Blunk T (2007) Long-term stable fibrin gels for cartilage engineering. Biomaterials 28:55–65
Fuchs E (2008) Skin stem cells: rising to the surface. J Cell Biol 180:273–284
Gazda LS, Vinerean HV, Laramore MA, Diehl CH, Hall RD, Rubin AL, Smith BH (2007) Encapsulation of porcine islets permits extended culture time and insulin independence in spontaneously diabetic BB rats. Cell Transplant 16:609–620
Grassl ED, Oegema TR, Tranquillo RT (2003) A fibrin-based arterial media equivalent. J Biomed Mater Res 66A:550–561
Harrison CA, MacNeil S (2008) The mechanism of skin graft contraction: an update on current research and potential future therapies. Burns 34:153–163
Herbert CB, Nagaswami C, Bittner GD, Hubbell JA, Weisel JW (1998) Effects of fibrin micromorphology on neurite growth from dorsal root ganglia cultured in three-dimensional fibrin gels. J Biomed Mater Res 40:551–559
Hong Y, Song HQ, Gong YH, Mao ZW, Gao CY, Shen JC (2007) Covalently crosslinked chitosan hydrogel: properties of in vitro degradation and chondrocyte encapsulation. Acta Biomater 3:23–31
Horn EM, Beaumont M, Shu XZ, Harvey A, Prestwich GD, Horn KM, Gibson AR, Preul MC, Panitch A (2007) Influence of cross-linked hyaluronic acid hydrogels on neurite outgrowth and recovery from spinal cord injury. J Neurosurg Spine 6:133–140
Hortelano G, Al Hendy A, Ofosu FA, Chang PL (1996) Delivery of human factor IX in mice by encapsulated recombinant myoblasts: a novel approach towards allogeneic gene therapy of hemophilia B. Blood 87:5095–5103
Hoshikawa A, Nakayama Y, Matsuda T, Oda H, Nakamura K, Mabuchi K (2006) Encapsulation of chondrocytes in photopolymerizable styrenated gelatin for cartilage tissue engineering. Tissue Eng 12:2333–2341
Hou TY, Xu JZ, Li Q, Feng JH, Zen L (2008) In vitro evaluation of a fibrin gel antibiotic delivery system containing mesenchymal stem cells and vancomycin alginate beads for treating bone infections and facilitating bone formation. Tissue Eng 14A:1173–1182
Hunt NC, Shelton RM, Grover LM (2009a) An alginate hydrogel matrix for the localised delivery of a fibroblast/keratinocyte co-culture. Biotechnol J 4:730–737
Hunt NC, Shelton RM, Grover LM (2009b) Reversible mitotic and metabolic inhibition of fibroblasts by alginate hydrogel encapsulation. Biomaterials 30:6435–6443
Ikada Y, Tabata Y (1996) Gelatin hydrogel as a matrix to release protein drugs. Abstr Paper Am Chem Soc Natl Meet 21:5–25
Janmey PA, Winer JP, Weisel JW (2009) Fibrin gels and their clinical and bioengineering applications. Interface 6:1–10
Joki T, Machluf M, Atala A, Zhu JH, Seyfried NT, Dunn IF, Abe T, Carroll RS, Black PM (2001) Continuous release of endostatin from microencapsulated engineered cells for tumor therapy. Nat Biotechnol 19:35–39
Keshaw H, Forbes A, Day RM (2005) Release of angiogenic growth factors from cells encapsulated in alginate beads with bioactive glass. Biomaterials 26:4171–4179
Khattak SF, Chin KS, Bhatia SR, Roberts SC (2007) Enhancing oxygen tension and cellular function in alginate cell encapsulation devices through the use of perfluorocarbons. Biotechnol Bioeng 96:156–166
Kong HJ, Smith MK, Mooney DJ (2003) Designing alginate hydrogels to maintain viability of immobilized cells. Biomaterials 24:4023–4029
Kretlow JD, Young S, Klouda L, Wong M, Mikos AG (2009) Injectable biomaterials for regenerating complex craniofacial tissues. Adv Mater 21:3368–3393
Lahooti S, Sefton MV (2000a) Effect of an immobilization matrix and capsule membrane permeability on the viability of encapsulated HEK cells. Biomaterials 21:987–995
Lahooti S, Sefton MV (2000b) Agarose enhances the viability of intraperitoneally implanted microencapsulated L929 fibroblasts. Cell Transplant 9:785–796
Lahooti S, Sefton MV (2000c) Microencapsulation of normal and transfected L929 fibroblasts in a HEMA-MMA copolymer. Tissue Eng 6:139–149
Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–1880
Liu HW, Ofosu FA, Chang PL (1993) Expression of human factor-IX by microencapsulated recombinant fibroblasts. Hum Gene Ther 4:291–301
MacNeil S (2007) Progress and opportunities for tissue-engineered skin. Nature 445:874–880
Marenzana M, Wilson-Jones N, Mudera V, Brown RA (2006) The origins and regulation of tissue tension: identification of collagen tension-fixation process in vitro. Exp Cell Res 312:423–433
Meana A, Iglesias J, Del Rio M, Larcher F, Madrigal B, Fresno MF, Martin C, San Roman F, Tevar F (1998) Large surface of cultured human epithelium obtained on a dermal matrix based on live fibroblast-containing fibrin gels. Burns 24:621–630
Mesa JM, Zaporojan V, Weinand C, Johnson TS, Bonassar L, Randolph MA et al (2006) Tissue engineering cartilage with aged articular chondrocytes in vivo. Plast Reconstr Surg 118:41–49
Miyoshi M, Kawazoe T, Igawa HH, Tabata Y, Ikada Y, Suzuki S (2005) Effects of bFGF incorporated into a gelatin sheet on wound healing. J Biomater Sci Polym Ed 16:893–907
Mol A, van Lieshout MI, Veen CGD, Neuenschwander S, Hoerstrup SP, Baaijens FPT, Bouten CVC (2005) Fibrin as a cell carrier in cardiovascular tissue engineering applications. Biomaterials 26:3113–3121
Murray MM, Forsythe B, Chen F, Lee SJ, Yoo JJ, Atala A, Steinert A (2006) The effect of thrombin on ACL fibroblast interactions with collagen hydrogels. J Orthop Res 24:508–515
Narayanan K, Leck KJ, Gao SJ, Wan ACA (2009) Three-dimensional reconstituted extracellular matrix scaffolds for tissue engineering. Biomaterials 30:4309–4317
Nazhat SN, Abou Neel EA, Kidane A, Ahmed I, Hope C, Kershaw M, Lee PD, Stride E, Saffari N, Knowles JC, Brown RA (2007) Controlled microchannelling in dense collagen scaffolds by soluble phosphate glass fibers. Biomacromolecules 8(2):543–551
Nisbet DR, Crompton KE, Horne MK, Finkelstein DI, Forsythe JS (2008) Neural tissue engineering of the CNS using hydrogels. J Biomed Mater Res B Appl Biomater 87B:251–263
Norman LL, Stroka K, Aranda-Espinoza H (2009) Guiding axons in the central nervous system: a tissue engineering approach. Tissue Eng B 15:291–305
Pachence JM (1996) Collagen-based devices for soft tissue repair. J Biomed Mater Res B Appl Biomater 33:35–40
Park SH, Park SR, Chung SI, Pai KS, Min BH (2005) Tissue-engineered cartilage using fibrin/hyaluronan composite gel and its in vivo implantation. Artif Organs 29:838–845
Pelaez D, Huang CYC, Cheung HS (2009) Cyclic compression maintains viability and induces chondrogenesis of human mesenchymal stem cells in fibrin gel scaffolds. Stem Cells Dev 18:93–102
Peppas NA, Hilt JZ, Khademhosseini A, Langer R (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18:1345–1360
Read TA, Farhadi M, Bjerkvig R, Olsen BR, Rokstad AM, Huszthy PC, Vajkoczy P (2001a) Intravital microscopy reveals novel antivascular and antitumor effects of endostatin delivered locally by alginate-encapsulated cells. Cancer Res 61:6830–6837
Read TA, Sorensen DR, Mahesparan R, Enger PO, Timpl R, Olsen BR, Hjelstuen MHB, Haraldseth O, Bjerkvig R (2001b) Local endostatin treatment of gliomas administered by microencapsulated producer cells. Nat Biotechnol 19:29–34
Rosa AL, de Oliveira PT, Beloti MM (2008) Macroporous scaffolds associated with cells to construct a hybrid biomaterial for bone tissue engineering. Expert Rev Med Dev 5:719–728
Rowley JA, Mooney DJ (2002) Alginate type and RGD density control myoblast phenotype. J Biomed Mater Res 60:217–223
Smith AM, Harris JJ, Shelton RM, Perrie Y (2007) 3D culture of bone-derived cells immobilised in alginate following light-triggered gelation. J Control Release 119:94–101
Soon-Shiong P (1999) Treatment of type I diabetes using encapsulated islets. Adv Drug Deliv Rev 35:259–270
Stegemann JP, Kaszuba SN, Rowe SL (2007) Review: advances in vascular tissue engineering using protein-based biomaterials. Tissue Eng 13:2601–2613
Sterodimas A, de Faria J, Correa WE, Pitanguy I (2009) Tissue engineering and auricular reconstruction: a review. J Plast Reconstr Aesthet Surg 62:447–452
Tuan TL, Song A, Chang S, Younai S, Nimni ME (1996) In vitro fibroplasia: matrix contraction, cell growth, and collagen production of fibroblasts cultured in fibrin gels. Exp Cell Res 223:127–134
Wang L, Shelton RM, Cooper PR, Lawson M, Triffit JT, Barralet JE (2003) Evaluation of sodium alginate for bone marrow cell tissue engineering. Biomaterials 24:3475–3481
Wang XH, Yan YN, Pan YQ, Xiong Z, Liu HX, Cheng B, Liu F, Lin F, Wu RD, Zhang RJ, Lu QP (2006) Generation of three-dimensional hepatocyte/gelatin structures with rapid prototyping system. Tissue Eng 12:83–90
Williams PL, Warwick R, Dyson M, Banniston LH (1989) Gray’s anatomy, 37th edn. Longman Group, London
Ye Q, Zund G, Benedikt P, Jockenhoevel S, Hoerstrup SP, Sakyama S, Hubbell JA, Turina M (2000) Fibrin gel as a three dimensional matrix in cardiovascular tissue engineering. Eur J Cardiothorac Surg 17:587–591
Young S, Wong M, Tabata Y, Mikos AG (2005) Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J Control Release 109:256–274
Zhang L, Webster TJ (2009) Nanotechnology and nanomaterials: promises for improved tissue regeneration. Nano Today 4:66–80
Zielinski BA, Aebischer P (1994) Chitosan as a matrix for mammalian-cell encapsulation. Biomaterials 15:1049–1056
Zimmermann H, Ehrhart F, Zimmermann D, Muller K, Katsen-Globa A, Behringer M, Feilen PJ, Gessner P, Zimmermann G, Shirley SG, Weber MM, Metze J, Zimmermann U (2007) Hydrogel-based encapsulation of biological, functional tissue: fundamentals, technologies and applications. Appl Phys Mater Sci Process 89:909–922
Author information
Authors and Affiliations
School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK
Nicola C. Hunt & Liam M. Grover
- Nicola C. Hunt
You can also search for this author inPubMed Google Scholar
- Liam M. Grover
You can also search for this author inPubMed Google Scholar
Corresponding author
Correspondence toLiam M. Grover.
Rights and permissions
About this article
Cite this article
Hunt, N.C., Grover, L.M. Cell encapsulation using biopolymer gels for regenerative medicine.Biotechnol Lett32, 733–742 (2010). https://doi.org/10.1007/s10529-010-0221-0
Received:
Revised:
Accepted:
Published:
Issue Date:
Share this article
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative