Skip to main content

Advertisement

SpringerLink
Log in

Injectable hydrogels for islet transplantation: a concise review

  • Review
  • Published:
Journal of Pharmaceutical Investigation Aims and scope Submit manuscript

Abstract

Islet cell transplantation is a promising alternative for the treatment of type 1 diabetic mellitus which is caused by complete absence or reduced insulin production by pancreas. After Shapiro and his team carried out successful islet transplantation and achieved positive clinical outcomes, much progress have been made in the procedure from isolation to clinical transplantation. Since 2000, more than 1500 patients have undergone islet transplantation. Thus, this therapeutic approach has progressed from mere curiosity to therapeutic achievement. However, many hurdles have yet to be crossed, such as instant blood-mediated inflammatory reaction, immune reactions, side effects of immunosuppressant drugs, lack of donors, islet quality variability, and others. Isolated islet cells face huge mechanical, immunological and bio-physiological challenges that potentially compromise long-term viability and functionality post-transplantation. In addition, preservation of islet cell microenvironment, including extracellular matrix (ECM), is one of the most challenging aspects of the transplantation. ECM is composed of water, proteins, and polysaccharides, and is essential for biochemical, mechanical, and physiological well-being of organs and tissues. ECM also organizes morphological integrity and physiological function by either binding with growth factors or promoting cell surface interactions that result in signal transduction and the regulation of gene transcription. In general, we can say ECM and other biochemical substances constitute a tissue-specific microenvironment that is responsible for growth and proliferation. In this review, we focus on ECM mimicking scaffolds, injectable natural and synthetic hydrogels, their recent advancements, some drawbacks, and future perspectives.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aamodt KI, Powers AC (2017) Signals in the pancreatic islet microenvironment influence beta-cell proliferation. Diabetes Obes Metab 19(Suppl 1):124–136

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmed EM (2015) Hydrogel: preparation, characterization, and applications: a review. J Adv Res 6(2):105–121

    CAS  PubMed  Google Scholar 

  • Ali A, Ahmed S (2018) A review on chitosan and its nanocomposites in drug delivery. Int J Biol Macromol 109:273–286

    CAS  PubMed  Google Scholar 

  • Alismail H, Jin S (2014) Microenvironmental stimuli for proliferation of functional islet beta-cells. Cell Biosci 4(1):12

    PubMed  PubMed Central  Google Scholar 

  • Andrades P, Asiedu C, Rodriguez C, Goodwin KJ, McCarn J, Thomas JM (2007) Subcutaneous pancreatic islet transplantation using fibrin glue as a carrier. Transplant Proc 39(1):191–192

    CAS  PubMed  Google Scholar 

  • Antoine EE, Vlachos PP, Rylander MN (2014) Review of collagen i hydrogels for bioengineered tissue. Microenvironments: characterization of mechanics, structure, and transport. Tissue Eng Part B Rev 20(6):683–696

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ashari N, Pang HW, Simon T, Xiong Y, Coburn JM, Bromberg JS et al (2018) Silk fibroin preserves beta cell function under inflammatory stress while stimulating islet cell surface GLUT2 expression. Cell Immunol 329:10–16

    CAS  PubMed  Google Scholar 

  • Assmann A, Hinault C, Kulkarni RN (2009) Growth factor control of pancreatic islet regeneration and function. Pediatr Diabetes 10(1):14–32

    CAS  PubMed  Google Scholar 

  • Augst AD, Kong HJ, Mooney DJ (2006) Alginate hydrogels as biomaterials. Macromol Biosci 6(8):623–633

    CAS  PubMed  Google Scholar 

  • Bateman JF, Boot-Handford RP, Lamandé SR (2009) Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations. Nat Rev Genet 10(3):173–183

    CAS  PubMed  Google Scholar 

  • Behonick DJ, Werb Z (2003) A bit of give and take: the relationship between the extracellular matrix and the developing chondrocyte. Mech Dev 120(11):1327–1336

    CAS  PubMed  PubMed Central  Google Scholar 

  • Belair DG, Le NN, Murphy WL (2014) Design of growth factor sequestering biomaterials. Chem Commun (Camb) 50(99):15651–15668

    CAS  Google Scholar 

  • Benninger RK, Head WS, Zhang M, Satin LS, Piston DW (2011) Gap junctions and other mechanisms of cell-cell communication regulate basal insulin secretion in the pancreatic islet. J Physiol 589(Pt 22):5453–5466

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bogdani M, Johnson PY, Potter-Perigo S, Nagy N, Day AJ, Bollyky PL, Wight TN (2014) Hyaluronan and hyaluronan-binding proteins accumulate in both human type 1 diabetic islets and lymphoid tissues and associate with inflammatory cells in insulitis. Diabetes 63(8):2727–2743

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bonner-Weir S, Smith FE (1994) Islet cell growth and the growth factors involved. Trends Endocrinol Metab 5(2):60–64

    CAS  PubMed  Google Scholar 

  • Bottino R, Knoll MF, Knoll CA, Bertera S, Trucco MM (2018) The future of islet transplantation is now. Front Med (Lausanne) 5:202

    Google Scholar 

  • Brissova M, Shostak A, Shiota M, Wiebe PO, Poffenberger G et al (2006) Pancreatic islet production of vascular endothelial growth factor—a is essential for islet vascularization, revascularization, and function. Diabetes 55(11):2974–2985

    CAS  PubMed  Google Scholar 

  • Brissova M, Aamodt K, Brahmachary P, Prasad N, Hong JY et al (2014) Islet microenvironment, modulated by vascular endothelial growth factor-A signaling, promotes beta cell regeneration. Cell Metab 19(3):498–511.b

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bruni A, Lopez BG, Pepper A, Abualhassan N, Shapiro A (2014) Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges. Diabetes Metab Syndr Obes 7:211–223

    CAS  PubMed  PubMed Central  Google Scholar 

  • Burczak K, Gamian E, Kochman A (1996) Long-term in vivo performance and biocompatibility of poly(vinyl alcohol) hydrogel macrocapsules for hybrid-type artificial pancreas. Biomaterials 17:2351–2356

    CAS  PubMed  Google Scholar 

  • Burdick JA, Prestwich GD (2011) Hyaluronic acid hydrogels for biomedical applications. Adv Mater 23(12):H41–H56

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cen L, Liu W, Cui L, Zhang W, Cao Y (2008) Collagen tissue engineering: development of novel biomaterials and applications. Pediatr Res 63(5):492

    CAS  PubMed  Google Scholar 

  • Chan BP, Leong KW (2008) Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J 17(Suppl 4):467–479

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chan AT, Karakas MF, Vakrou S, Afzal J, Rittenbach A et al (2015) Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment. Biomaterials 73:1–11

    CAS  PubMed  PubMed Central  Google Scholar 

  • Charriere G, Bejot M, Schnitzler L, Ville G, Hartmann DJ (1989) Reactions to a bovine collagen implant. Clinical and immunologic study in 705 patients. J Am Acad Dermatol 21(6):1203–1208

    CAS  PubMed  Google Scholar 

  • Chen XG, Wang Z, Liu WS, Park HJ (2002) The effect of carboxymethyl-chitosan on proliferation and collagen secretion of normal and keloid skin fibroblasts. Biomaterials 23(23):4609–4614

    CAS  PubMed  Google Scholar 

  • Chhabra P, Brayman KL (2011) Current status of immunomodulatory and cellular therapies in preclinical. J Transplant 2011:637692

    PubMed  PubMed Central  Google Scholar 

  • Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems and apoptosis. Free Radic Biol Med 48(6):749–762

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cirulli V (2015) Cadherins in islet beta-cells: more than meets the eye. Diabetes 64(3):709–711

    CAS  PubMed  Google Scholar 

  • Cooper DK, Matsumoto S, Abalovich A, Itoh T, Mourad NI et al (2016) Progress in clinical encapsulated islet xenotransplantation. Transplantation 100(11):2301–2308

    CAS  PubMed  PubMed Central  Google Scholar 

  • Davis NE, Beenken-Rothkopf LN, Mirsoian A, Kojic N, Kaplan DL, Barron AE, Fontaine MJ (2012) Enhanced function of pancreatic islets co-encapsulated with ECM proteins and mesenchymal stromal cells in a silk hydrogel. Biomaterials 33(28):6691–6697

    CAS  PubMed  PubMed Central  Google Scholar 

  • Demirtas TT, Irmak G, Gumusderelioglu M (2017) A bioprintable form of chitosan hydrogel for bone tissue engineering. Biofabrication 9(3):035003

    PubMed  Google Scholar 

  • Diez JA, Arrojo E, Drigo R, Zheng X, Stelmashenko OV, Chua M et al (2017) Pancreatic islet blood flow dynamics in primates. Cell Rep 20(6):1490–1501

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dong H, Fahmy TM, Metcalfe SM, Morton SL, Dong X et al (2012) Immuno-isolation of pancreatic islet allografts using pegylated nanotherapy leads to long-term normoglycemia in full MHC mismatch recipient mice. PLoS One 7(12):e50265

    CAS  PubMed  PubMed Central  Google Scholar 

  • Du X, Zhou J, Shi J, Xu B (2015) Supramolecular hydrogelators and hydrogels: from soft matter to molecular biomaterials. Chem Rev 115(24):13165–13307

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eaglstein WH, Alvarez OM, Auletta M, Leffel D, Rogers GS et al (1999) Acute excisional wounds treated with a tissue-engineered skin (Apligraf). Dermatol Surg 25(3):195–201

    CAS  PubMed  Google Scholar 

  • El-Sherbiny IM, Yacoub MH (2013) Hydrogel scaffolds for tissue engineering: Progress and challenges. Glob Cardiol Sci Pract 38:316–342

    Google Scholar 

  • Erlandsen SL (1980) Types of pancreatic islet cells and their immunocytochemical identification. Monogr Pathol 21:140–155

    CAS  PubMed  Google Scholar 

  • Esni F, Täljedal IB, Perl AK, Cremer H, Christofori G, Semb H (1999) Neural cell adhesion molecule (N-CAM) is required for cell type segregation and normal ultrastructure in pancreatic islets. J Cell Biol 144(2):325–337

    CAS  PubMed  PubMed Central  Google Scholar 

  • Espona-Noguera A, Ciriza J, Cañibano-Hernández A, Fernandez L, Ochoa I et al (2018) Tunable injectable alginate-based hydrogel for cell therapy in type 1 diabetes mellitus. Int J Biol Macromol 107(Pt A):1261–1269

    CAS  PubMed  Google Scholar 

  • Fakhari A, Berkland C (2013) Applications and emerging trends of hyaluronic acid in tissue engineering, as a dermal filler, and in osteoarthritis treatment. Acta Biomater 9(7):7081–7092

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frantz C, Stewart KM, Weaver VM (2010) The extracellular matrix at a glance. J Cell Sci 123(Pt 24):4195–4200

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frisch SM, Vuori K, Ruoslahti E, Chan-Hui PY (1996) Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol 134(3):793–799

    CAS  PubMed  Google Scholar 

  • Gamian E, Kochman A, Rabczyński J, Burczak K (1999) Biocompatibility testing and function of a pancreatic prosthesis consisting of viable pancreatic islets encapsulated in PVA macrocapsules. Polim Med 29(1–2):3–20

    PubMed  Google Scholar 

  • Geckil H, Xu F, Zhang X, Moon S, Demirci U (2010) Engineering hydrogels as extracellular matrix mimics. Nanomedicine (Lond) 5(3):469–484

    CAS  Google Scholar 

  • Glowacki J, Mizuno S (2008) Collagen scaffolds for tissue engineering. Biopolymers 89(5):338–344

    CAS  PubMed  Google Scholar 

  • González-Henríquez CM, Sarabia-Vallejos MA, Rodriguez-Hernandez J (2017) Advances in the fabrication of antimicrobial hydrogels for biomedical applications. Materials (Basel) 10(3):232

    Google Scholar 

  • Goyal R, Guvendiren M, Freeman O, Kohn J (2017) Optimization of polymer-ECM composite scaffolds for tissue engineering: effect of cells and culture conditions on polymeric nanofiber mats. J Funct Biomater 8(1):1

    CAS  PubMed Central  Google Scholar 

  • Grajower MM (2018) Hypoglycemia in the elderly with diabetes: a growing problem with emerging solutions. Endocr Pract 24(3):312–314

    PubMed  Google Scholar 

  • Guan X, Avci-Adali M, Alarçin E, Cheng H, Kashaf SS et al (2017) Development of hydrogels for regenerative engineering. Biotechnol J 12(5):1600394

    Google Scholar 

  • Guilherme MR, Moia TA, Reis AV, Paulino AT, Rubira AF et al (2009) Synthesis and water absorption transport mechanism of a pH-sensitive polymer network structured on vinyl-functionalized pectin. Biomacromol 10(1):190–196

    CAS  Google Scholar 

  • Hadjipanayi E, Kuhn PH, Moog P, Bauer AT, Kuekrek H et al (2015) The fibrin matrix regulates angiogenic responses within the hemostatic microenvironment through biochemical control. PLoS One 10(8):e0135618

    PubMed  PubMed Central  Google Scholar 

  • Hagbard L, Cameron K, August P, Penton C, Parmar M, Hay DC, Kallur T (2018) Developing defined substrates for stem cell culture and differentiation. Philos Trans R Soc Lond B Biol Sci 373(1750):20170230

    PubMed  PubMed Central  Google Scholar 

  • Hakim NS (2002) Pancreatic transplantation for patients with type I diabetes. HPB (Oxford) 4(2):59–61

    Google Scholar 

  • Hals IK, Rokstad AM, Strand BL, Oberholzer J, Grill V (2013) Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. J Diabetes Res 2013:374925

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hamilton DC, Shih HH, Schubert RA, Michie SA, Staats PN, Kaplan DL, Fontaine MJ (2017) A silk-based encapsulation platform for pancreatic islet transplantation improves islet function in vivo. J Tissue Eng Regen Med 11(3):887–895

    CAS  PubMed  Google Scholar 

  • Haque MR, Lee DY, Ahn CH, Jeong JH, Byun Y (2014) Local co-delivery of pancreatic islets and liposomal clodronate using injectable hydrogel to prevent acute immune reactions in a type 1 diabetes. Pharm Res 31(9):2453–2462

    CAS  PubMed  Google Scholar 

  • Harlan DM, Kenyon NS, Korsgren O, Roep BO (2009) Current advances and travails in islet transplantation. Diabetes 58(10):2175–2184

    CAS  PubMed  PubMed Central  Google Scholar 

  • Harrington S, Williams J, Rawal S, Ramachandran K, Stehno-Bittel L (2017) Hyaluronic acid/collagen hydrogel as an alternative to alginate for long-term immunoprotected islet transplantation. Tissue Eng Part A 23(19–20):1088–1099

    CAS  PubMed  PubMed Central  Google Scholar 

  • Headen DM, Woodward KB, Coronel MM, Shrestha P, Weaver JD, Zhao H et al (2018) Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance. Nat Mater 17(8):732–739

    CAS  PubMed  PubMed Central  Google Scholar 

  • Health Quality Ontario (2015) Pancreas islet transplantation for patients with type 1 diabetes mellitus: a clinical evidence review. Ont Health Technol Assess Ser 15(16):1–84

    PubMed Central  Google Scholar 

  • Hinderer S, Layland SL, Schenke-Layland K (2016) ECM and ECM-like materials—biomaterials for applications in regenerative medicine and cancer therapy. Adv Drug Deliv Rev 97:260–269

    CAS  PubMed  Google Scholar 

  • Hogan MF, Hull RL (2017) The islet endothelial cell: a novel contributor to beta cell secretory dysfunction in diabetes. Diabetologia 60(6):952–959

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hokugo A, Takamoto T, Tabata Y (2006) Preparation of hybrid scaffold from fibrin and biodegradable polymer fiber. Biomaterials 27(1):61–67

    CAS  PubMed  Google Scholar 

  • Holdcraft RW, Gazda LS, Circle L, Adkins H, Harbeck SG et al (2014) Enhancement of in vitro and in vivo function of agarose-encapsulated porcine islets by changes in the islet microenvironment. Cell Transplant 23(8):929–944

    PubMed  Google Scholar 

  • Holland C, Numata K, Rnjak-Kovacina J, Seib F(2018) The biomedical use of silk: past, present, future. Adv Healthc Mater 8(1):e1800465

    PubMed  Google Scholar 

  • Huang Y, Chang Y (2014) Regulation of pancreatic islet beta-cell mass by growth factor and hormone signaling. Prog Mol Biol Transl Sci 121:321–349

    CAS  PubMed  Google Scholar 

  • Hull RL, Bogdani M, Nagy N, Johnson PY, Wight TN (2015) Hyaluronan: a mediator of islet dysfunction and destruction in diabetes? J Histochem Cytochem 63(8):592–603

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hynd MR, Turner JN, Shain W (2007) Applications of hydrogels for neural cell engineering. J Biomater Sci Polym Ed 18(10):1223–1244

    CAS  PubMed  Google Scholar 

  • Im GB, Bhang SH (2018) Recent research trend in cell and drug delivery system for type 1 diabetes treatment. J Pharm Investig 48:175–185

    CAS  Google Scholar 

  • Irving-Rodgers HF, Choong FJ, Hummitzsch K, Parish CR, Rodgers RJ et al (2014) Pancreatic islet basement membrane loss and remodeling after mouse islet isolation and transplantation: impact for allograft rejection. Cell Transplant 23(1):59–72

    CAS  PubMed  Google Scholar 

  • Ito M, Taguchi T (2009) Enhanced insulin secretion of physically crosslinked pancreatic beta-cells by using a poly(ethylene glycol) derivative with oleyl groups. Acta Biomater 5(8):2945–2952

    CAS  PubMed  Google Scholar 

  • Iwata H, Amemiya H, Matsuda T, Takano H, Hayashi R, Akutsu T (1989) Evaluation of microencapsulated islets in agarose gel as bioartificial pancreas by studies of hormone secretion in culture and by xenotransplantation. Diabetes 38(Suppl 1):224–225

    PubMed  Google Scholar 

  • Janmey PA, Winer JP, Weisel JW (2009) Fibrin gels and their clinical and bioengineering applications. J R Soc Interface 6(30):1–10

    CAS  PubMed  Google Scholar 

  • Jansson L, Barbu A, Bodin B, Drott CJ, Espes D et al (2016) Pancreatic islet blood flow and its measurement. Ups J Med Sci 121(2):81–95

    PubMed  PubMed Central  Google Scholar 

  • Järveläinen H, Sainio A, Koulu M, Wight TN, Penttinen R (2009) Extracellular matrix molecules: potential targets in pharmacotherapy. Pharmacol Rev 61(2):198–223

    PubMed  PubMed Central  Google Scholar 

  • Johansson U, Ria M, Åvall K, Dekki Shalaly N, Zaitsev SV et al (2015) Pancreatic islet survival and engraftment is promoted by culture on functionalized spider silk matrices. PLoS One 10(6):e0130169

    PubMed  PubMed Central  Google Scholar 

  • Jung H, Kim YY, Kim B, Nam H, Suh JG (2017) Improving glycemic control in model mice with type 2 diabetes by increasing superoxide dismutase (SOD) activity using silk fibroin hydrolysate (SFH). Biochem Biophys Res Commun 493(1):115–119

    CAS  PubMed  Google Scholar 

  • Kim JS, Lim JH, Nam HY, Lim HJ, Shin JS et al (2012) In situ application of hydrogel-type fibrin-islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation. J Controll Release 162(2):382–390

    CAS  Google Scholar 

  • Kleinman HK, Martin GR (2005) Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol 15(5):378–386

    CAS  PubMed  Google Scholar 

  • Knobeloch T, Abadi SEM, Bruns J, Zustiak SP, Kwon G (2017) Injectable polyethylene glycol hydrogel for islet encapsulation: an in vitro and in vivo characterization. Biomed Phys Eng Express 3:035022

    PubMed  PubMed Central  Google Scholar 

  • Kopecek J (2007) Hydrogel biomaterials: a smart future? Biomaterials 28(34):5185–5192

    CAS  PubMed  PubMed Central  Google Scholar 

  • Korpos É, Kadri N, Kappelhoff R, Wegner J, Overall CM et al (2013) The peri-islet basement membrane, a barrier to infiltrating leukocytes in type 1 diabetes in mouse and human. Diabetes 62(2):531–542

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kragl M, Lammert E (2010) Basement membrane in pancreatic islet function. Adv Exp Med Biol 654:217–234

    CAS  PubMed  Google Scholar 

  • Kuehn C, Lakey JR, Lamb MW, Vermette P (2013) Young porcine endocrine pancreatic islets cultured in fibrin show improved resistance toward hydrogen peroxide. Islets 5(5):207–215

    PubMed  PubMed Central  Google Scholar 

  • Kumar M, Gupta P, Bhattacharjee S, Nandi SK, Mandal BB (2018) Immunomodulatory injectable silk hydrogels maintaining functional islets and promoting anti-inflammatory M2 macrophage polarization. Biomaterials 187:1–17

    CAS  PubMed  Google Scholar 

  • Latifi N, Asgari M (2018) A tissue-mimetic nano-fibrillar hybrid injectable hydrogel for potential soft tissue engineering applications. Sci Rep 8(1):1047

    PubMed  PubMed Central  Google Scholar 

  • Lee JH, Kim HW (2018) Emerging properties of hydrogels in tissue engineering. J Tissue Eng 9:2041731418768285

    PubMed  PubMed Central  Google Scholar 

  • Lee KY, Mooney DJ (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37(1):106–126

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lei Y, Gojgini S, Lam J, Segura T (2011) The spreading, migration and proliferation of mouse mesenchymal stem cells cultured inside hyaluronic acid hydrogels. Biomaterials 32(1):39–47

    CAS  PubMed  Google Scholar 

  • Leigh CM, Edwin N (1997) Immunocytochemical identification of cells containing insulin, glucagon, somatostatin, and pancreatic polypeptide in islets of Langerhans of the wombat pancreas with electron microscopy. Eur J Histochem 41(3):217–221

    CAS  PubMed  Google Scholar 

  • Leslie-Barbick JE, Moon JJ, West JL (2009) Covalently-immobilized vascular endothelial growth factor promotes endothelial cell tubulogenesis in poly(ethylene glycol) diacrylate hydrogels. J Biomater Sci Polym Ed 20(12):1763–1779

    CAS  PubMed  Google Scholar 

  • Leslie-Barbick JE, Saik JE, Gould DJ, Dickinson ME, West JL (2011) The promotion of microvasculature formation in poly(ethylene glycol) diacrylate hydrogels by an immobilized VEGF-mimetic peptide. Biomaterials 32(25):5782–5789

    CAS  PubMed  Google Scholar 

  • Li Y, Meng H, Liu H, Lee BP (2015) Fibrin gel as an injectable biodegradable scaffold and cell carrier for tissue engineering. Sci World J 2015:685690

    Google Scholar 

  • Liang Y, Walczak P, Bulte JW (2013) The survival of engrafted neural stem cells within hyaluronic acid hydrogels. Biomaterials 34(22):5521–5529

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lieleg O, Ribbeck K (2011) Biological hydrogels as selective diffusion barriers. Trends Cell Biol 21(9):543–551

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lim JY, Min BH, Kim BG, Han HJ, Kim SJ et al (2009) A fibrin gel carrier system for islet transplantation into kidney subcapsule. Acta Diabetol 46(3):243–248

    CAS  PubMed  Google Scholar 

  • Liu X, Yang Y, Li Y, Niu X, Zhao B, Wang Y, Bao C, Xie Z, Lin Q, Zhu L (2017) Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale 9(13):4430–4438

    CAS  PubMed  Google Scholar 

  • Llacua LA, Faas MM3, de Vos P (2018) Extracellular matrix molecules and their potential contribution to the function of transplanted pancreatic islets. Diabetologia 61(6):1261–1272

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lu P, Takai K, Weaver VM, Werb Z (2011) Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 3(12):a005058

    PubMed  PubMed Central  Google Scholar 

  • Magaz A, Faroni A (2018) Bioactive silk-based nerve guidance conduits for augmenting peripheral nerve repair. Adv Healthc Mater 7:e1800308

    PubMed  Google Scholar 

  • Mahou R, Zhang DKY, Vlahos AE, Sefton MV (2017) Injectable and inherently vascularizing semi-interpenetrating polymer network for delivering cells to the subcutaneous space. Biomaterials 131:27–35

    CAS  PubMed  Google Scholar 

  • Malafaya PB, Silva GA, Reis RL (2007) Natural–origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev 59(4–5):207–233

    CAS  PubMed  Google Scholar 

  • Mallick KK, Cox SC (2013) Biomaterial scaffolds for tissue engineering. Front Biosci (Elite Ed) 5:341–360

    Google Scholar 

  • Manandhar S, Kothandan VK, Yoo JO, Hwang J, Hwang SR (2018) A pharmaceutical investigation into exosomes. J Pharm Investig 48:617–626

    CAS  Google Scholar 

  • Mao D, Zhu M, Zhang X, Ma R, Yang X et al (2017) A macroporous heparin-releasing silk fibroin scaffold improves islet transplantation outcome by promoting islet revascularisation and survival. Acta Biomater 59:210–220

    CAS  PubMed  Google Scholar 

  • Marchioli G, Luca AD, de Koning E, Engelse M, Van Blitterswijk CA et al (2016) Hybrid polycaprolactone/alginate scaffolds functionalized with VEGF to promote de novo vessel formation for the transplantation of islets of langerhans. Adv Healthc Mater 5(13):1606–1616

    CAS  PubMed  Google Scholar 

  • Marchioli G, Zellner L, Oliveira C, Engelse M, Koning E, Mano J, Apeldoorn AV, Moroni L (2017) Layered PEGDA hydrogel for islet of Langerhans encapsulation and improvement of vascularization. J Mater Sci Mater Med 28(12):195

    PubMed  PubMed Central  Google Scholar 

  • Mason MN, Mahoney MJ (2009) Selective beta-cell differentiation of dissociated embryonic pancreatic precursor cells cultured in synthetic polyethylene glycol hydrogels. Tissue Eng Part A 15(6):1343–1352

    CAS  PubMed  Google Scholar 

  • Mason MN, Arnold CA, Mahoney MJ (2009a) Entrapped collagen type 1 promotes differentiation of embryonic pancreatic precursor cells into glucose-responsive beta-cells when cultured in three-dimensional PEG hydrogels. Tissue Eng Part A 15(12):3799–3808

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mason MN, Arnold CA, Mahoney MJ (2009b) Entrapped collagen type 1 promotes differentiation of embryonic pancreatic precursor cells into glucose-responsive β-cells when cultured in three-dimensional PEG hydrogels. Tissue Eng Part A 15(12):3799–3808

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mazzocchi A, Devarasetty M, Huntwork R, Soker S, Skardal A (2018) Optimization of collagen type I-hyaluronan hybrid bioink for 3D bioprinted liver microenvironments. Biofabrication 11:015003

    PubMed  Google Scholar 

  • McBane JE, Vulesevic B, Padavan DT, McEwan KA, Korbutt GS, Suuronen EJ (2013) Evaluation of a collagen-chitosan hydrogel for potential use as a pro-angiogenic site for islet transplantation. PLoS One 8(10):e77538

    CAS  PubMed  PubMed Central  Google Scholar 

  • McCall AL, Farhy LS (2013) Treating type 1 diabetes: from strategies for insulin delivery to dual hormonal control. Minerva Endocrinol 38(2):145–163

    CAS  PubMed  PubMed Central  Google Scholar 

  • McEwan K, Padavan DT, Ellis C, McBane JE, Vulesevic B, Korbutt GS, Suuronen EJ (2016) Collagen-chitosan-laminin hydrogels for the delivery of insulin-producing tissue. J Tissue Eng Regen Med 10(10):E397–E408

    CAS  PubMed  Google Scholar 

  • McGuigan AP, Sefton MV (2007) Modular tissue engineering: fabrication of a gelatin-based construct. J Tissue Eng Regen Med 1(2):136–145

    CAS  PubMed  Google Scholar 

  • Meda P (1996) Gap junction involvement in secretion: the pancreas experience. Clin Exp Pharmacol Physiol 23(12):1053–1057

    CAS  PubMed  Google Scholar 

  • Mesquida P, Kohl D, Andriotis OG (2018) Evaluation of surface charge shift of collagen fibrils exposed to glutaraldehyde. Sci Rep 8(1):10126

    PubMed  PubMed Central  Google Scholar 

  • Moon S, Hasan SK, Song YS, Xu F, Keles HO et al (2010) Layer by layer three-dimensional tissue epitaxy by cell-laden hydrogel droplets. Tissue Eng Part C Methods 16(1):157–166

    CAS  PubMed  Google Scholar 

  • Moriarty N, Cabré S, Alamilla V, Pandit A, Dowd E (2018) Encapsulation of young donor age dopaminergic grafts in a GDNF-loaded collagen hydrogel further increases their survival, reinnervation, and functional efficacy after intrastriatal transplantation in hemi-Parkinsonian rats. Eur J Neurosci. https://doi.org/10.1111/ejn.14090

    Article  PubMed  Google Scholar 

  • Najjar M, Manzoli V, Abreu M, Villa C, Martino MM et al (2015) Fibrin gels engineered with pro-angiogenic growth factors promote engraftment of pancreatic islets in extrahepatic sites in mice. Biotechnol Bioeng 112(9):1916–1926

    CAS  PubMed  Google Scholar 

  • Nikolova G, Jabs N, Konstantinova I, Domogatskaya A, Tryggvason K et al (2006) The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation. Dev Cell 10(3):397–405

    CAS  PubMed  Google Scholar 

  • Nomi M, Atala A, Coppi PD, Soker S (2002) Principals of neovascularization for tissue engineering. Mol Aspects Med 23(6):463–483

    CAS  PubMed  Google Scholar 

  • O’Sullivan ES, Vegas A, Anderson DG (2011) Islets transplanted in immunoisolation devices: a review of the progress and the challenges that remain. Endocr Rev 32(6):827–844

    PubMed  PubMed Central  Google Scholar 

  • Papakonstantinou E, Roth M, Karakiulakis G (2012) Hyaluronic acid: a key molecule in skin aging. Dermatoendocrinol 4(3):253–258

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pareta R, McQuilling JP, Sittadjody S, Jenkins R, Bowden S et al (2014) Long-term function of islets encapsulated in a re-designed alginate microcapsule construct in omentum pouches of immune-competent diabetic rats. Pancreas 43(4):605–613

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pathak S, Regmi S, Gupta B, Poudel BK, Pham TT (2017) Single synchronous delivery of FK506-loaded polymeric microspheres with pancreatic islets for the successful treatment of streptozocin-induced diabetes in mice. Drug Deliv 24(1):1350–1359

    CAS  PubMed  Google Scholar 

  • Pathak S, Regmi S, Nguyen TT, Gupta B, Gautam M (2018) Polymeric microsphere-facilitated site-specific delivery of quercetin prevents senescence of pancreatic islets in vivo and improves transplantation outcomes in mouse model of diabetes. Acta Biomater 75:287–299

    CAS  PubMed  Google Scholar 

  • Phelps EA, Headen DM, Taylor WR, Thulé PM, García AJ (2013) Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes. Biomaterials 34(19):4602–4611

    CAS  PubMed  PubMed Central  Google Scholar 

  • Phelps EA, Templeman KL, Thulé PM, García AJ (2015) Engineered VEGF-releasing PEG-MAL hydrogel for pancreatic islet vascularization. Drug Deliv Transl Res 5(2):125–136

    CAS  PubMed  PubMed Central  Google Scholar 

  • Qi M (2014) Transplantation of encapsulated pancreatic islets as a treatment for patients with type 1 diabetes mellitus. Adv Med 2014:429710

    PubMed  PubMed Central  Google Scholar 

  • Qi M, Gu Y, Sakata N, Kim D, Shirouzu Y, Yamamoto C, Hiura A, Sumi S, Inoue K (2004) PVA hydrogel sheet macroencapsulation for the bioartificial pancreas. Biomaterials 25(27):5885–5892

    CAS  PubMed  Google Scholar 

  • Qi M, Mørch Y, Lacík I, Formo K, Marchese E, Wang Y et al (2012a) Survival of human islets in microbeads containing high guluronic acid alginate cross-linked with Ca(2+) and Ba(2+). Xenotransplantation 19(6):355–364

    PubMed  PubMed Central  Google Scholar 

  • Qi Z, Yamamoto C, Imori N, Kinukawa A, Yang KC, Yanai G et al (2012b) Immunoisolation effect of polyvinyl alcohol (PVA) macroencapsulated islets in type 1 diabetes therapy. Cell Transplant 21(2–3):525–534

    PubMed  Google Scholar 

  • Ramadan AA, Elbakry AM, Esmaeil AH (2018) Pharmaceutical and pharmacokinetic evaluation of novel rectal mucoadhesive hydrogels containing tolmetin sodium. J Pharm Investig 48(6):673–683

    CAS  PubMed  Google Scholar 

  • Ravi S, Caves JM, Martinez AW, Haller CA, Chaikof EL (2013) Incorporation of fibronectin to enhance cytocompatibility in multilayer elastin-like protein scaffolds for tissue engineering. J Biomed Mater Res A 101(7):1915–1925

    Google Scholar 

  • Riopel M, Trinder M, Wang R (2015) Fibrin, a scaffold material for islet transplantation and pancreatic endocrine tissue engineering. Tissue Eng Part B Rev 21(1):34–44

    CAS  PubMed  Google Scholar 

  • Risbud M, Hardikar A, Bhonde R (2000) Chitosan-polyvinyl pyrrolidone hydrogels as candidate for islet immunoisolation: in vitro biocompatibility evaluation. Cell Transplant 9(1):25–31

    CAS  PubMed  Google Scholar 

  • Risbud M, Bhonde M, Bhonde R (2001) Chitosan-polyvinyl pyrrolidone hydrogel does not activate macrophages: potentials for transplantation applications. Cell Transplant 10(2):195–202

    CAS  PubMed  Google Scholar 

  • Rostami M, Mostafa R, Mozhgan K, Danafar H (2017) Sol–gel synthesis and characterization of zinc ferrite–graphene nano-hybrids for photo-catalytic degradation of the paracetamol. J Pharm Investig 48:657–664

    Google Scholar 

  • Ruoslahti E (1996) RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol 12:697–715

    CAS  PubMed  Google Scholar 

  • Sahni A, Francis CW (2000) Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation. Blood 96(12):3772–3778

    CAS  PubMed  Google Scholar 

  • Schuetz C, Markmann JF (2016) Islet cell transplant: Update on current clinical trials. Curr Transplant Rep 3(3):254–263

    PubMed  PubMed Central  Google Scholar 

  • Shapiro AMJ (2012) Islet transplantation in type 1 diabetes: ongoing challenges, refined procedures, and long-term outcome. Rev Diabet Stud 9(4):385–406

    PubMed  Google Scholar 

  • Shimizu H, Ohashi K, Utoh R, Ise K, Gotoh M, Yamato M, Okano T (2009) Bioengineering of a functional sheet of islet cells for the treatment of diabetes mellitus. Biomaterials 30(30):5943–5949

    CAS  PubMed  Google Scholar 

  • Simon HU, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5(5):415–418

    CAS  PubMed  Google Scholar 

  • Singh A, Peppas NA (2014) Hydrogels and scaffolds for immunomodulation. Adv Mater 26(38):6530–6541

    CAS  PubMed  PubMed Central  Google Scholar 

  • Somasundaram R, Ruehl M, Tiling N, Ackermann R, Schmid M et al (2000) Collagens serve as an extracellular store of bioactive interleukin 2. J Biol Chem 275(49):38170–38175

    CAS  PubMed  Google Scholar 

  • Steiner DJ, Kim A, Miller K, Hara M (2010) Pancreatic islet plasticity: Interspecies comparison of islet architecture and composition. Islets 2(3):135–145

    PubMed  PubMed Central  Google Scholar 

  • Stewart MH, Bendall SC, Bhatia M (2008) Deconstructing human embryonic stem cell cultures: niche regulation of self-renewal and pluripotency. J Mol Med (Berl) 86(8):875–886

    Google Scholar 

  • Su J, Hu BH, Lowe WL Jr, Kaufman DB, Messersmith PB (2010) Anti-inflammatory peptide-functionalized hydrogels for insulin-secreting cell encapsulation. Biomaterials 31(2):308–314

    CAS  PubMed  Google Scholar 

  • Suntornnond R, Tan EYS, An J, Chua CK (2017) A highly printable and biocompatible hydrogel composite for direct printing of soft and perfusable vasculature-like structures. Sci Rep 7(1):16902

    PubMed  PubMed Central  Google Scholar 

  • Tao SC, Guo SC, Li M, Ke QF, Guo YP, Zhang CQ (2017) Chitosan wound dressings incorporating exosomes derived from MicroRNA-126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model. Stem Cells Transl Med 6(3):736–747

    CAS  PubMed  Google Scholar 

  • Tashiro H, Iwata H, Warnock GL, Takagi T, Machida H, Ikada Y, Tsuji T (1997) Characterization and transplantation of agarose microencapsulated canine islets of Langerhans. Ann Transplant 2(3):33–39

    CAS  PubMed  Google Scholar 

  • Tezono K, Sarker KP, Kikuchi H, Nasu M, Kitajima I, Maruyama I (2001) Bioactivity of the vascular endothelial growth factor trapped in fibrin clots: production of IL-6 and IL-8 in monocytes by fibrin clots. Haemostasis 31(2):71–79

    CAS  PubMed  Google Scholar 

  • Theis V, Theiss C (2018) VEGF—a stimulus for neuronal development and regeneration in the CNS and PNS. Curr Protein Pept Sci 19(6):589–597

    CAS  PubMed  Google Scholar 

  • Tibbitt MW, Anseth KS (2009) Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng 103(4):655–663

    CAS  PubMed  PubMed Central  Google Scholar 

  • Totani T, Teramura Y, Iwata H (2008) Immobilization of urokinase on the islet surface by amphiphilic poly(vinyl alcohol) that carries alkyl side chains. Biomaterials 29(19):2878–2883

    CAS  PubMed  Google Scholar 

  • Van der Windt DJ, Echeverri GJ, Ijzermans JN, Cooper DK (2008) The choice of anatomical site for islet transplantation. Cell Transplant 17(9):1005–1014

    PubMed  Google Scholar 

  • Varoni E, Tschon M, Palazzo B, Nitti P, Martini L, Rimondini L (2012) Agarose gel as biomaterial or scaffold for implantation surgery: characterization, histological and histomorphometric study on soft tissue response. Connect Tissue Res 53(6):548–554

    CAS  PubMed  Google Scholar 

  • Velten F, Laue C, Schrezenmeir J (1999) The effect of alginate and hyaluronate on the viability and function of immunoisolated neonatal rat islets. Biomaterials 20(22):2161–2167

    CAS  PubMed  Google Scholar 

  • Vernon RB, Preisinger A, Gooden MD, D’Amico LA, Yue BB et al (2012) Reversal of diabetes in mice with a bioengineered islet implant incorporating a type I collagen hydrogel and sustained release of vascular endothelial growth factor. Cell Transplant 21(10):2099–2110

    PubMed  Google Scholar 

  • Virtanen I, Banerjee M, Palgi J, Korsgren O, Lukinius A et al (2008) Blood vessels of human islets of Langerhans are surrounded by a double basement membrane. Diabetologia 51(7):1181–1191

    CAS  PubMed  Google Scholar 

  • Vogler EA (2012) Protein adsorption in three dimensions. Biomaterials 33(5):1201–1237

    CAS  PubMed  Google Scholar 

  • Vukicevic S, Kleinman HK, Luyten FP, Roberts AB, Roche NS, Reddi AH (1992) Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components. Exp Cell Res 202(1):1–8

    CAS  PubMed  Google Scholar 

  • Weaver JD, Headen DM, Aquart J, Johnson CT2, Shea LD et al (2017) Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. Sci Adv 3(6):e1700184

    PubMed  PubMed Central  Google Scholar 

  • Weaver JD, Headen DM, Coronel MM, Hunckler MD, Shirwan H, Garcia AJ (2018) Synthetic poly(ethylene glycol)-based microfluidic islet encapsulation reduces graft volume for delivery to highly vascularized and retrievable transplant site. Am J Transplant. https://doi.org/10.1111/ajt.15168

    Article  PubMed  Google Scholar 

  • Weber LM, Cheung CY, Anseth KS (2008) Multifunctional pancreatic islet encapsulation barriers achieved via multilayer PEG hydrogels. Cell Transplant 16(10):1049–1057

    PubMed  Google Scholar 

  • Weber LM, Lopez CG, Anseth KS (2009) Effects of PEG hydrogel crosslinking density on protein diffusion and encapsulated islet survival and function. J Biomed Mater Res A 90(3):720–729

    PubMed  PubMed Central  Google Scholar 

  • World Health Organization (2016) Global report on diabetes. ISBN 978 92 4 156525 7 (NLM classification: WK 810)

  • Yang S, Leong KF, Du Z, Chua CK (2002) The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. Tissue Eng 8(1):1–11

    CAS  PubMed  Google Scholar 

  • Yang KC, Wu CC, Lin FH, Qi Z, Kuo TF, Cheng YH, Chen MP, Sumi S (2008) Chitosan/gelatin hydrogel as immunoisolative matrix for injectable bioartificial pancreas. Xenotransplantation 15(6):407–416

    PubMed  Google Scholar 

  • Yang KC, Qi Z, Wu CC, Shirouza Y, Lin FH, Yanai G, Sumi S (2010) The cytoprotection of chitosan based hydrogels in xenogeneic islet transplantation: an in vivo study in streptozotocin-induced diabetic mouse. Biochem Biophys Res Commun 393(4):818–823

    CAS  PubMed  Google Scholar 

  • Yao D, Qian Z, Zhou J, Peng G, Zhou G, Liu H, Fan Y (2018) Facile incorporation of REDV into porous silk fibroin scaffolds for enhancing vascularization of thick tissues. Mater Sci Eng C Mater Biol Appl 93:96–105

    CAS  PubMed  Google Scholar 

  • Yeh HC, Brown TT, Maruthur N, Ranasinghe P, Berger Z, Suh YD et al (2012) Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Ann Intern Med 157(5):336–347

    PubMed  Google Scholar 

  • Yin N, Han Y, Xu H, Gao Y, Yi T, Yao J, Dong L, Cheng D, Chen Z (2016) VEGF-conjugated alginate hydrogel prompt angiogenesis and improve pancreatic islet engraftment and function in type 1 diabetes. Mater Sci Eng C Mater Biol Appl 59:958–964

    CAS  PubMed  Google Scholar 

  • Yue B (2014) Biology of the extracellular matrix: an overview. J Glaucoma S20–S23

    PubMed  Google Scholar 

  • Zarrintaj P, Manouchehri S, Ahmadi Z, Saeb MR, Urbanska AM, Kaplan DL, Mozafari M (2018) Agarose-based biomaterials for tissue engineering. Carbohydr Polym 187:66–84

    CAS  PubMed  Google Scholar 

  • Zhang Y, Zhou Z, Sun L, Liu Z, Xia X, Tao TH (2018) “Genetically engineered” biofunctional triboelectric nanogenerators using recombinant spider silk. Adv Mater e1805722

  • Zhu J, Marchant RE (2011) Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devices 8(5):607–626

    PubMed  PubMed Central  Google Scholar 

  • Zisch AH, Lutolf MP, Ehrbar M, Raeber GP, Rizzi SC et al (2003) Cell-demanded release of VEGF from synthetic, biointeractive cell ingrowth matrices for vascularized tissue growth. Faseb J 17(15):2260–2262

    CAS  PubMed  Google Scholar 

  • Zou F, Zhou J, Zhang J, Li J, Tang B, Chen W, Wang J, Wang X (2018) Functionalization of silk with in-situ synthesized platinum nanoparticles. Materials (Basel) 11(10):1929

    PubMed Central  Google Scholar 

  • Zustiak SP, Wei Y, Leach JB (2013) Protein-hydrogel interactions in tissue engineering: mechanisms and applications. Tissue Eng Part B Rev 19(2):160–171

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Pathak Shiva for invaluable advice and detailed review of the paper. This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Korean Ministry of Science, ICT, and Future Planning (Grant No. 2015R1A5A2009124 and 2016M3A9B6903321) and funded by the Ministry of Education (Grant No. 2017R1D1A1B03027831); and by the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI) and the Korean Ministry of Health and Welfare (Grant No. HI18C0453).

Author information

Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, 280 Daehak˗ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea

    Prakash Shrestha, Shobha Regmi & Jee-Heon Jeong

Authors
  1. Prakash Shrestha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shobha Regmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jee-Heon Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jee-Heon Jeong.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human and animal rights

This article does not contain any studies with human and animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shrestha, P., Regmi, S. & Jeong, JH. Injectable hydrogels for islet transplantation: a concise review. J. Pharm. Investig. 50, 29–45 (2020). https://doi.org/10.1007/s40005-019-00433-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-019-00433-3

Keywords

Search

Navigation