Incorporation of nanoparticles into transplantable decellularized matrices: Applications and challenges

Abstract

Decellularization of tissues can significantly improve regenerative medicine and tissue engineering by producing natural, less immunogenic, three-dimensional, acellular matrices with high biological activity for transplantation. Decellularized matrices retain specific critical components of native tissues such as stem cell niche, various growth factors, and the ability to regenerate in vivo. However, recellularization and functionalization of these matrices remain limited, highlighting the need to improve the characteristics of decellularized matrices. Incorporating nanoparticles into decellularized tissues can overcome these limitations because nanoparticles possess unique properties such as multifunctionality and can modify the surface of decellularized matrices with additional growth factors, which can be loaded onto the nanoparticles. Therefore, in this minireview, we highlight the various approaches used to improve decellularized matrices with incorporation of nanoparticles and the challenges present in these applications.

Keywords

Decellularization matrices nanoparticles regenerative medicine scaffold tissue engineering

Get full access to this article

View all access options for this article.

References

Londono

Badylak

. Biologic scaffolds for regenerative medicine: mechanisms of in vivo remodeling. Ann Biomed Eng 2015; 43(3): 577–592.

White

Taylor

Faulk

et al . The impact of detergents on the tissue decellularization process: a ToF-SIMS study. Acta Biomater 2017; 50: 207–219.

Wang

Bao

et al . Genipin crosslinking reduced the immunogenicity of xenogeneic decellularized porcine whole-liver matrices through regulation of immune cell proliferation and polarization. Sci Rep 2016; 6: 24779.

Hussein

Park

K-M

Kang

K-S

et al . Heparin-gelatin mixture improves vascular reconstruction efficiency and hepatic function in bioengineered livers. Acta Biomater 2016; 38: 82–93.

Shevach

Fleischer

Shapira

et al . Gold nanoparticle-decellularized matrix hybrids for cardiac tissue engineering. Nano Lett 2014; 14(10): 5792–5796.

Yudintceva

Nashchekina

Blinova

et al . Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells. Int J Nanomedicine 2016; 11: 4521–4533.

Galanzha

Shashkov

Kelly

et al . In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells. Nat Nanotechnol 2009; 4(12): 855–860.

Hachani

Lowdell

Birchall

et al . Tracking stem cells in tissue-engineered organs using magnetic nanoparticles. Nanoscale 2013; 5(23): 11362–11373.

Smith

Lyon

. Multifunctional nanogels for siRNA delivery. Acc Chem Res 2012; 45(7): 985–993.

10.

Bakhru

Furtado

Morello

et al . Oral delivery of proteins by biodegradable nanoparticles. Adv Drug Deliv Rev 2013; 65(6): 811–821.

11.

Kingsley

Ranjan

Dasgupta

et al . Nanotechnology for tissue engineering: need, techniques and applications. J Pharm Res 2013; 7(2): 200–204.

12.

Nakanishi

Takarada

Yamaguchi

et al . Recent advances in cell micropatterning techniques for bioanalytical and biomedical sciences. Anal Sci 2008; 24(1): 67–72.

13.

Inai

Kotaki

et al . Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials 2004; 25(5): 877–886.

14.

Yang

Murugan

Wang

et al . Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials 2005; 26(15): 2603–2610.

15.

Zhang

. Fabrication of novel biomaterials through molecular self-assembly. Nat Biotechnol 2003; 21(10): 1171–1178.

16.

Kim

D-H

Smith

Kim

et al . Nanopatterned cardiac cell patches promote stem cell niche formation and myocardial regeneration. Integr Biol 2012; 4(9): 1019–1033.

17.

Elkhenany

Bourdo

Hecht

et al . Graphene nanoparticles as osteoinductive and osteoconductive platform for stem cell and bone regeneration. Nanomedicine 2017; 13(7): 2117–2126.

18.

Poggetti

Battistini

Parchi

et al . How to direct the neuronal growth process in peripheral nerve regeneration: future strategies for nanosurfaces scaffold and magnetic nanoparticles. Surg Technol Int 2017; 30: 458–461.

19.

Lee

S-J

Zhu

Heyburn

et al . Development of novel 3-D printed scaffolds with core-shell nanoparticles for nerve regeneration. IEEE T Biomed Eng 2017; 64(2): 408–418.

20.

Sanad

RA-B

Abdel-Bar

. Chitosan-hyaluronic acid composite sponge scaffold enriched with andrographolide-loaded lipid nanoparticles for enhanced wound healing. Carbohydr Polym 2017; 173: 441–450.

21.

Alberts

Johnson

Lewis

et al . The extracellular matrix of animals. In: Telser

David

(eds) Molecular biology of the cell. 4th ed. New York: Garland Science, 2002, pp. 1090–1117.

22.

Mecham

. Overview of extracellular matrix. Curr Protoc Cell Biol 2012; 57: 1011011–1011016.

23.

Deng

Dong

Shi

et al . Application of decellularized scaffold combined with loaded nanoparticles for heart valve tissue engineering in vitro. J Huazhong Univ Sci Technol Med Sci 2011; 31(1): 88–93.

24.

Ravindran

Chandran

Khan

. Biofunctionalized silver nanoparticles: advances and prospects. Colloids Surf B Biointerfaces 2013; 105: 342–352.

25.

Karakoti

Das

Thevuthasan

et al . PEGylated inorganic nanoparticles. Angew Chem Int Ed 2011; 50(9): 1980–1994.

26.

Deeken

Bachman

Ramshaw

et al . Characterization of bionanocomposite scaffolds comprised of mercaptoethylamine-functionalized gold nanoparticles crosslinked to acellular porcine tissue. J Mater Sci Mater Med 2012; 23(2): 537–546.

27.

Nair

Ameer

Alison

et al . A gold nanoparticle coated porcine cholecyst-derived bioscaffold for cardiac tissue engineering. Colloids Surf B Biointerfaces 2017; 157: 130–137.

28.

Smith

Snider

Gilley

et al . Homogenized porcine extracellular matrix derived injectable tissue construct with gold nanoparticles for musculoskeletal tissue engineering applications. J Biomater Nanobiotechnol 2017; 8(2): 125–143.

29.

Deeken

Fox

Bachman

et al . Characterization of bionanocomposite scaffolds comprised of amine-functionalized gold nanoparticles and silicon carbide nanowires crosslinked to an acellular porcine tendon. J Biomed Mater Res B Appl Biomater 2011; 97(2): 334–344.

30.

Moura

Segundo

Neves

et al . Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application. Int J Nanomedicine 2014; 9: 4911–4922.

31.

Ivanov

Bednar

Haes

. Investigations of the mechanism of gold nanoparticle stability and surface functionalization in capillary electrophoresis. ACS Nano 2009; 3(2): 386–394.

32.

Sanskriti

Upadhyay

. Cysteine, homocysteine and glutathione guided hierarchical self-assemblies of spherical silver nanoparticles paving the way for their naked eye discrimination in human serum. New J Chem 2017; 41(11): 4316–4321.

33.

Jazayeri

Amani

Pourfatollah

et al . Various methods of gold nanoparticles (GNPs) conjugation to antibodies. Sens Biosens Res 2016; 9: 17–22.

34.

Cheraghipour

Tamaddon

Javadpour

et al . PEG conjugated citrate-capped magnetite nanoparticles for biomedical applications. J Magn Magn Mater 2013; 328: 91–95.

35.

Jahan

Haddadi

. Investigation and optimization of formulation parameters on preparation of targeted anti-CD205 tailored PLGA nanoparticles. Int J Nanomedicine 2015; 10: 7371–7384.

36.

Tan

Tang

et al . Controlled release of chitosan/heparin nanoparticle-delivered VEGF enhances regeneration of decellularized tissue-engineered scaffolds. Int J Nanomedicine 2011; 6: 929–942.

37.

Jiang

Lin

Jiang

et al . Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits. Sci Rep 2016; 6: 20784.

38.

Ostdiek

Ivey

Hansen

et al . Feasibility of a nanomaterial-tissue patch for vascular and cardiac reconstruction. J Biomed Mater Res B Appl Biomater 2016; 104(3): 449–457.

39.

Shimizu

Ito

Arinobe

et al . Effective cell-seeding technique using magnetite nanoparticles and magnetic force onto decellularized blood vessels for vascular tissue engineering. J Biosci Bioeng 2007; 103(5): 472–478.

40.

Ostdiek

Ivey

Grant

et al . An in vivo study of a gold nanocomposite biomaterial for vascular repair. Biomaterials 2015; 65: 175–183.

41.

Ostdiek

Grant

. Mechanical and in vitro characterisation of decellularised porcine aortic tissue conjugated with gold nanoparticles as a vascular repair material. Int J Nano Biomater 2015; 6(1): 1–17.

42.

Cozad

Bachman

Grant

. Assessment of decellularized porcine diaphragm conjugated with gold nanomaterials as a tissue scaffold for wound healing. J Biomed Mater Res A 2011; 99(3): 426–434.

43.

Deeken

Esebua

Bachman

et al . Assessment of the biocompatibility of two novel, bionanocomposite scaffolds in a rodent model. J Biomed Mater Res B Appl Biomater 2011; 96(2): 351–359.

44.

Grant

Deeken

Hamilton

et al . A comparative study of the remodeling and integration of a novel AuNP-tissue scaffold and commercial tissue scaffolds in a porcine model. J Biomed Mater Res A 2013; 101(10): 2778–2787.

45.

Grant

Cozad

Grant

et al . In vitro electromagnetic stimulation to enhance cell proliferation in extracellular matrix constructs with and without metallic nanoparticles. J Biomed Mater Res B Appl Biomater 2015; 103(8): 1532–1540.

46.

Grant

Smith

Schmidt

et al . In vivo bone tunnel evaluation of nanoparticle-grafts using an ACL reconstruction rabbit model. J Biomed Mater Res A 2017; 105(4): 1071–1082.

47.

Ramesh

Chandrasekaran

Jeevankumar

et al . Hybrid amniotic membrane dressing with green silver nanoparticles as bioengineered skin for wounds and burns: a pilot studies. J Biotechnol Biomater 2017; 7(272): 2.

48.

Geng

Song

et al . Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix. Nanoscale Res Lett 2011; 6(1): 312.

49.

Jiang

Xiong

et al . VEGF-loaded nanoparticle-modified BAMAs enhance angiogenesis and inhibit graft shrinkage in tissue-engineered bladder. Ann Biomed Eng 2015; 43(10): 2577–2586.

50.

Kang

Deng

et al . Functional nanoparticles activate a decellularized liver scaffold for blood detoxification. Small 2016; 12(15): 2067–2076.

51.

Saleh

Ahmed

et al . Silver nanoparticles improve structural stability and biocompatibility of decellularized porcine liver. Artif Cells Nanomed Biotechnol. Epub ahead of print 27 March 2018. DOI: 10.1080/21691401.2018.1457037.

52.

Dennis

Whitlow

Detamore

et al . Hyaluronic-acid-hydroxyapatite colloidal gels combined with micronized native ECM as potential bone defect fillers. Langmuir 2017; 33(1): 206–218.

53.

Francisco

Mogharbel

Cunha

et al . 15d-PGJ2-loaded in nanoparticles associated with decellurazied human amniotic membrane scaffold: a potential anti-inflammatory delivery system. Front Nanosci Nanotechnol 2016; 2(2): 111–113.

54.

Borschel

Huang

Y-C

Calve

et al . Tissue engineering of recellularized small-diameter vascular grafts. Tissue Eng 2005; 11(5–6): 778–786.

55.

Deeken

Cozad

Bachman

et al . Characterization of bionanocomposite scaffolds comprised of amine-functionalized single-walled carbon nanotubes crosslinked to an acellular porcine tendon. J Biomed Mater Res A 2011; 96(3): 584–594.

56.

Augustine

Kalarikkal

Thomas

. Advancement of wound care from grafts to bioengineered smart skin substitutes. Prog Biomater 2014; 3(2–4): 103–113.

57.

Kwan

Liu

et al . Modulation of collagen alignment by silver nanoparticles results in better mechanical properties in wound healing. Nanomedicine 2011; 7(4): 497–504.

58.

Galili

. Acceleration of wound healing by α-gal nanoparticles interacting with the natural anti-gal antibody. J Immunol Res 2015; 2015: 589648.

59.

Galili

. Macrophages recruitment and activation by α-gal nanoparticles accelerate regeneration and can improve biomaterials efficacy in tissue engineering. Open Tissue Eng Regen Med J 2013; 6(1)1: 1–11.

60.

Bolland

Korossis

Wilshaw

S-P

et al . Development and characterisation of a full-thickness acellular porcine bladder matrix for tissue engineering. Biomaterials 2007; 28(6): 1061–1070.

61.

Brown

Farhat

Merguerian

et al . 22 week assessment of bladder acellular matrix as a bladder augmentation material in a porcine model. Biomaterials 2002; 23(10): 2179–2190.

62.

Zhu

Feng

et al . Bladder reconstruction with adipose-derived stem cell-seeded bladder acellular matrix grafts improve morphology composition. World J Urol 2010; 28(4): 493–498.

63.

Rippel

Ghanbari

Seifalian

. Tissue-engineered heart valve: future of cardiac surgery. World J Surg 2012; 36(7): 1581–1591.

64.

Simon

Kasimir

Seebacher

et al . Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients. Eur J Cardiothorac Surg 2003; 23(6): 1002–1006.

65.

Qian

Yong

et al . Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering. Mater Sci Eng C Mater Biol Appl 2014; 36: 95–101.

66.

Laschke

Strohe

Menger

et al . In vitro and in vivo evaluation of a novel nanosize hydroxyapatite particles/poly (ester-urethane) composite scaffold for bone tissue engineering. Acta Biomater 2010; 6(6): 2020–2027.

67.

Zhou

Touny

Bhaduri

. Fabrication of novel PLA/CDHA bionanocomposite fibers for tissue engineering applications via electrospinning. J Mater Sci Mater Med 2011; 22(5): 1183–1193.

68.

Fan

Chu

Rawls

et al . Development of an antimicrobial resin—a pilot study. Dent Mater 2011; 27(4): 322–328.

69.

Hebeish

Hashem

El-Hady

et al . Development of CMC hydrogels loaded with silver nano-particles for medical applications. Carbohydr Polym 2013; 92(1): 407–413.

70.

Alarcon

Udekwu

Noel

et al . Safety and efficacy of composite collagen-silver nanoparticle hydrogels as tissue engineering scaffolds. Nanoscale 2015; 7(44): 18789–18798.

71.

Nie

Wang

et al . In vivo study of biodistribution and urinary excretion of surface-modified silica nanoparticles. Anal Chem 2008; 80(24): 9597–9603.

72.

Niidome

Yamagata

Okamoto

et al . PEG-modified gold nanorods with a stealth character for in vivo applications. J Control Release 2006; 114(3): 343–347.

73.

Akiyama

Mori

Katayama

et al . The effects of PEG grafting level and injection dose on gold nanorod biodistribution in the tumor-bearing mice. J Control Release 2009; 139(1): 81–84.

74.

Brede

Labhasetwar

. Applications of nanoparticles in the detection and treatment of kidney diseases. Adv Chronic Kidney Dis 2013; 20(6): 454–465.

75.

Hagens

Oomen

de Jong

et al . What do we (need to) know about the kinetic properties of nanoparticles in the body? Regul Toxicol Pharmacol 2007; 49(3): 217–229.

76.

Brown

Wilson

MacNee

et al . Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicol Appl Pharmacol 2001; 175(3): 191–199.

77.

Soenen

Parak

Rejman

et al . (Intra)cellular stability of inorganic nanoparticles: effects on cytotoxicity, particle functionality, and biomedical applications. Chem Rev 2015; 115(5): 2109–2135.

78.

Paulsson

Krag

Frederiksen

et al . Conductance of alkanedithiol single-molecule junctions: a molecular dynamics study. Nano Lett 2009; 9(1): 117–121.

79.

Cole

David

Wang

et al . Magnetic brain tumor targeting and biodistribution of long-circulating PEG-modified, cross-linked starch-coated iron oxide nanoparticles. Biomaterials 2011; 32(26): 6291–6301.

80.

Feliu

Docter

Heine

et al . In vivo degeneration and the fate of inorganic nanoparticles. Chem Soc Rev 2016; 45(9): 2440–2457.

81.

Punnakitikashem

Ravikumar

et al . Extracellular matrix coating enhances nanoparticle uptake by lung epithelial cells. Am Heart Assoc Circ Res 2015; 117(1): A28.

82.

H-L

Mao

K-L

C-T

et al . An injectable acellular matrix scaffold with absorbable permeable nanoparticles improves the therapeutic effects of docetaxel on glioblastoma. Biomaterials 2016; 107: 44–60.