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Scaffolds for Cartilage Regeneration: To Use or Not to Use?

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Bioinspired Biomaterials

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1249 ))

Abstract

Joint cartilage has been a significant focus on the field of tissue engineering and regenerative medicine (TERM) since its inception in the 1980s. Represented by only one cell type, cartilage has been a simple tissue that is thought to be straightforward to deal with. After three decades, engineering cartilage has proven to be anything but easy. With the demographic shift in the distribution of world population towards ageing, it is expected that there is a growing need for more effective options for joint restoration and repair. Despite the increasing understanding of the factors governing cartilage development, there is still a lot to do to bridge the gap from bench to bedside. Dedicated methods to regenerate reliable articular cartilage that would be equivalent to the original tissue are still lacking. The use of cells, scaffolds and signalling factors has always been central to the TERM. However, without denying the importance of cells and signalling factors, the question posed in this chapter is whether the answer would come from the methods to use or not to use scaffold for cartilage TERM. This paper presents some efforts in TERM area and proposes a solution that will transpire from the ongoing attempts to understand certain aspects of cartilage development, degeneration and regeneration. While an ideal formulation for cartilage regeneration has yet to be resolved, it is felt that scaffold is still needed for cartilage TERM for years to come.

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Acknowledgement

The authors thanked the Ministry of Education (MOE) Malaysia Transdisciplinary Research Grant Scheme TRGS/1/2016/UIAM/02/8/2 (TRGS16-02-002-0002) under TRGS/1/2016/UIAM/02/8 programme and the Ministry of Energy, Science, Technology, Environment and Climate Change (MESTECC, formerly known as MOSTI) Malaysia Science Fund (SF14-012-0062/06-01-08-SF0238); the Kulliyyah of Allied Health Sciences, International Islamic University Malaysia (IIUM), Kuantan Campus, Pahang, Malaysia; and Tissue Engineering and Regenerative Medicine Research Team, IIUM, for their support.

Author information

Authors and Affiliations

  1. Department of Physical Rehabilitation Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan, Pahang, Malaysia

    Munirah Sha’ban

  2. Department of Biomedical Science, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan, Pahang, Malaysia

    Muhammad Aa’zamuddin Ahmad Radzi

Authors
  1. Munirah Sha’ban
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  2. Muhammad Aa’zamuddin Ahmad Radzi
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Corresponding author

Correspondence to Munirah Sha’ban .

Editor information

Editors and Affiliations

  1. Institute of Cell & Tissue Engineering and College of Medicine, Catholic University of Korea, Seoul, Korea (Republic of)

    Heung Jae Chun

  2. 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Guimarães, Portugal

    Rui L. Reis

  3. Department of Industrial Engineering and BIOtech Research Center, University of Trento, Trento, Italy

    Antonella Motta

  4. Department of BIN Convergence Technology, Department of Polymer Nano Science & Technology and Polymer BIN Research Center, Jeonbuk National University, Jeonju, Korea (Republic of)

    Gilson Khang

Appendix

Appendix

List of biomaterial scaffolds used as an individual or in combination in cartilage tissue engineering experimentation based on 1645 studies starting 1994 to 2017. Note Table (A) natural biomaterials and (B) synthetic biomaterials.

(A) Natural biomaterials

1. Agarose

2. Collagen type I (Integra®) commercial

3. Hyaluronic acid (HYAFF®-11)

4. Fibrin

5. Alginate

6. Collagen I

7. Collagen I/GAG

8. Gelatin

9. Calcium phosphate tribasic

10. Collagen type I

11. Collagen II

12. Hyaluronic acid, alginate (NS) [NS]

13. Silicone rubber membranes coated with type I collagen; ~agarose

14. Atelocollagen I

15. Silk fibroin

16. Calcium polyphosphate

17. Chitosan

18. HYAFF-11; HYAFF-11-S

19. Sodium alginate

20. Methacrylated form of hyaluronan (HA-MA) (hydrogel, cylindrical) [Photocross-linking]

21. Collagen type I (Cellagen™) commercial

22. Self-assembling collagen type I

23. Alginate; agarose; gelatin; fibrin

24. Agarose; alginate; gelatin

25. B-TCP

26. Cartilage ECM

27. Hyaluronic acid methacrylated

28. Bacterial cellulose; collagen type II; alginate

29. Hyaluronan

30. Self-assembled (collagen type II-coated; aggrecan-coated); ~agarose

31. Collagen I; II; III

32. Pellet; ~atelocollagen

33. Fibrinogen

34. Hyaluronic acid;{atelocollagen}

35. Hyaluronic acid (HA) hydrogels (2 wt% 1100 kDa, 2 wt% 350 kDa, 5 wt% 350 kDa, 2 wt% 50 kDa, 5 wt% 50 kDa, 10 wt% 50 kDa; 20 wt% 50 kDa)

36. Pellet; ~collagen

37. Macroporous gelatin-coated microcarrier beads CultiSpher

38. Gelatin (photopolymerisable styrenated gelatin)

39. Alginate beads; agarose

40. CaReS (rat-tail collagen type I); atelocollagen (bovine collagen type I); dermal regeneration template (bovine collagen type I); Chondro-Gide (bovine collagen type I/III); atelocollagen honeycomb small (bovine collagen type I); atelocollagen honeycomb large (bovine collagen type I)

41. Human amniotic membrane (epithelial side of intact HAM (IHE), basement side of denuded HAM (DHB) and stromal side of denuded HAM (DHS))

42. Collagen type I (Resorba®) commercial

43. Collagen

44. ECM (cell-derived)

45. Pellets vitro and vivo; ~alginate gel vivo

46. Micromass; collagen honeycomb

47. Osteochondral cores (cylindrical) [NS]

48. Collagen I (Antema®) commercial

49. Pellet → engineered ECM

50. Collagen type II

51. Alginate hydrogel; agarose hydrogel

52. Hyaluronan biomaterial (HYAFF-11, Fidia) {cylinder} [NS]

53. Alginate bead → coralline hydroxyapatite

54. Hyaluronic acid {hydrogels}

55. Decellularised (cartilage ECM)

56. Collagen I (Helistat®) commercial

57. Chitosan + Arg-Gly-Asp (RGD); chitosan + epidermal growth factor (EGF)

58. Coral

59. Whole blood, agarose

60. Cell sheet → cell plate in culture insert; ~atelocollagen honeycomb-shaped

61. Chitin (di-butyryl-chitin)

62. Alginate beads → calcium phosphate Calcibon®

63. Cellulose

64. Gellan gum

65. Hyaluronic acid HA (0.5, 1 and 2 g)

66. Aragonite matrix

67. Layered agarose hydrogel

68. Chondron ECM

69. Cross-linked methacrylated hyaluronic acid hydrogels (MeHA);{agarose}

70. HA; agarose {gel}

71. Collagen II (recombinant human)

72. Calcium alginate

73. Gelatin, chitosan (cylindrical) [NS]

74. Gellan um;{agarose}

75. Alginate (hydrogel) [NS]; demineralised bone matrix (NS) [3D printing]

76. Atelocollagen

77. Hyaluronic acid (nonwoven mesh) [NS]

78. Decellularised (osteochondral graft)

79. Demineralised joint condyle

80. Alginate beads; ~hydroxyapatite (HA) carrier

81. Collagen type I (CaRes®)

82. Collagen I (CaReS®)

83. Hydroxyapatite, chitin, chitosan (NS) [NS]

84. Collagen type I (Arthro Kinetics Biotechnology)

85. Collagen (Chondro-Gide®)

86. Pellet; cross-linkable hyaluronan hydrogel

87. Decellularised osteochondral explant

88. Gelatin; chitosan

89. Silk fibroin;{hyaluronic acid (HYAFF®-11)}

90. Fibrin glue hydrogel; platelet-rich fibrin glue hydrogel; fibrin glue hydrogel containing heparin-binding delivery system; platelet-rich fibrin glue hydrogel containing heparin-binding delivery system

91. Nonbiomedical and biomedical grade alginates

92. Collagen I (Porcogen™)

93. Sodium alginate (Sea Matrix®)

94. Methacrylated glycol chitosan

95. Collagen type I, collagen type III (disc) [NS]

96. Self-assembled; fibrin

97. Collagen I (Ultrafoam®) commercial

98. Pellet culture; agarose

99. Hyaluronic acid (HA) hydrogel; agarose hydrogel

100. Hyaluronic acid methacrylated; agarose

101. κ-Carrageenan

102. “Hydrogel: (1) soluble rat-tail type I collagen (0.2% w/v) (BD Biosciences, San Jose, CA, USA); (2) type I collagen (0.2%) incorporating transglutaminase (TG)-2 (100 lgml–1) (Sigma); (3) type I collagen (0.2%) incorporating microbial transglutaminase (mTG; 100 lg ml–1) (Ajinomoto Food Ingredients LLC, Chicago, IL); (4) type I collagen (0.2%) incorporating genipin (GP, 0.25 mM) (Wako, Richmond, VA, USA); (5) type I collagen (0.2%) incorporating GP (0.25 mM) and control agarose beads (without heparin) (Sigma); and (6) type I collagen (0.2%) incorporating GP (0.25 mM) and heparin-agarose type I beads (10% weight of heparin/weight of collagen) (Sigma)

103. Sponge-like scaffolds were prepared: (1) porcine type I/III collagen (CI) (0.5% w/v) (Geistlich Biomaterials, Wolhusen, Switzerland); (2) CI (0.5%) additionally supplemented with CS (7% w/w relative to CI) (Sigma Chemical Co., St Louis, MO, USA); and (3) CI (0.5%) additionally supplemented with HS (7% w/w relative to CI) (Sigma)”

104. Cell pellet – collagen type II nanoarchitectured molecules; collagen fibrils (CNFs); collagen spheres (CNPs)

105. Gelatin; chitosan; agarose

106. Decellularised (dermal ECM)

107. Hyaluronic acid (HYAFF®-11); collagen (Bio-Gide®) commercial

108. Self-assembled (agarose mould) → collagen cross-linking via lysyl oxidase (timing)

109. Collagen type I (PureCol®) commercial

110. Bacterial cellulose

111. Pellet culture (aggregate);~micromass (self-assembled) in plate; ~collagen II

112. Devitalised cartilage explant

113. Alginate (beads) [NS]; cell pellet (NS) [NS]; collagen, chitosan (NS) [NS]

114. Alginate bead → scaffold free on b-tricalcium phosphate carriers []

115. Fibrin hydrogel in agarose well; agarose well only

116. Osteochondral cores, agarose (disc) [NS]

117. Extracellular matrix (ECM) by ASCs; ECM by synovium-derived stem cells (SDSCs). The cell in pellet condition

118. TCP

119. Glycerol phosphate

120. Decalcified bone matrix

121. Hyaluronic acid hydrogel

122. Recombinant human collagen type II (Fibrinogen Europe, Helsinki, Finland)

123. PRP

124. Micromass; pellet culture model; vivo~fibrin gel

125. Injectable hydroxypropylmethylcellulose (HPMC) hydrogel

126. Hyaluronic acid methacrylate (HA-MA), chondroitin sulphate methacrylate (CS-MA); (hydrogel) [NS]

127. Collagen type I, collagen type III (NS) [NS]

128. Sulphated alginate

129. Agarose; plasma; whole blood

130. Photocross-linkable gelatin-methacrylamide (Gel-MA); varying concentrations (0–2%) of hyaluronic acid methacrylate (HA-MA)

131. Human acellular cartilage matrix powders

132. Self-assembled (polyethylene terephthalate (PET)-coated); agarose hydrogel encapsulation

133. Methacrylated gelatin

134. ECM (MSC-derived)

135. Demineralised bone matrix

136. Hybrid organic-inorganic (HOI) material photopolymer ORMOSIL SZ2080; ∗collagen type I membrane

137. Decellularised (meniscus ECM)

138. Alginate; chitosan; fibrin

139. Heparin-conjugated fibrin (gel) [NS]

140. Microcavitary alginate hydrogel (microsphere)

141. Chondroitin sulphate methacrylate

142. Micromass cell pellets; alginate hydrogels

143. 45S5 Bioglass®

144. Graphene oxide (NS) [NS]

145. Amniotic membrane

146. Hyaluronic acid (NS) [NS]

147. Collagen type I, collagen type II, hydroxyapatite (cylindrical) [NS]

148. Porcine articular cartilage extracellular matrix (ACECM) (disc) [directional crystallisation and freeze-drying]

149. Cartilage ECM powder

150. Self-assembled; ~alginate

151. Pellet; ECM hydrogel

152. RGD-immobilised microcavitary alginate hydrogels; microcavitary alginate hydrogel

153. Gelatin methacryloyl

154. Gelatin methacrylamide (GelMA), hyaluronic acid methacrylate (HAMA), alginate (ALG), hydroxyapatite paste (HAP) (hydrogel) [3D printing]

155. Chitosan; alginate; collagen I

156. Demineralised cancellous bone

157. Human dermal fibroblast-derived ECM (hECM)

158. Decellularised (cartilage ECM) and methacrylated; methacrylated gelatin

159. Calcium-cobalt alginate

160. Devitalised cartilage

161. Transglutaminase-cross-linked hyaluronan hydrogels (HA-TG); alginate

162. Pellet; alginate bead; {monolayer}

163. ECM

164. Alginate; agarose

165. Decellularised (bone matrix) and demineralised

166. Gelatin methacrylamide; polyacrylamide

167. Pellets; agarose

168. Monomeric type I and type II collagen

169. Sodium alginate, collagen type I, collagen type II, chondroitin sulphate (hydrogel) [NS]

(B) Synthetic biomaterials

1. 2-Hydroxyethyl methacrylate-L-lactate–dextran (HEMA–LLA–D)

2. B-TCP

3. Calcium carbonate (Calcibon®)

4. Calcium polyphosphate

5. Cell pellet; ~PLGA

6. Collagen-like proteins

7. Compact polyelectrolyte complexes (CoPECs)

8. Elastin-like polypeptide (ELP)

9. Hyaluronan benzyl ester (disc) [NS]

10. Injectable PLGA microsphere

11. Macromers of PEG-caprolactone (PEG-CAP) endcapped with norbornene (PEG-CAP-NOR)

12. Nonporous microcarriers poly(lactic-co-glycolic acid) (PLGA); porous PLGA; amine-functionalised PLGA-NH2

13. Nonwoven PGA fibres

14. Nonwoven polyethylene terephthalate fibre

15. NS polycarbonate membrane

16. Oligo(trimethylene carbonate)-poly(ethylene glycol)-oligo (trimethylene carbonate) diacrylate (TPT-DA)

17. OPF

18. PBT

19. PCL

20. PEG

21. PEG hydrogel; PLGA microfibers

22. PEGDA

23. PEGDM

24. PEG–oligo(lactic acid) dimethacrylate PEG–LA-DM

25. Peptide-modified PEGDA (hydrogel) [NS]

26. PGA

27. PGA; PLGA (disc) [NS]

28. PGA; PLLA; PDLLA; PLGA; PCL

29. PGA-PLA (Ethisorb 210); poly-L-lactic acid

30. PGLA (polyglycollic-co-lactic acid)

31. PHBV (3-hydroxybutrate-co-3-hydroxyvalerate)

32. PLA

33. PLA (OPLA®)

34. PLA; PGA; PLGA

35. PLAG

36. PLCL

37. PLG

38. PLGA

39. PLGA, poly(ethy1ene oxide)-dimethacrylate, poly(ethy-1-ene glycol) (NS) [double emulsion]

40. PLGA; polydioxanone (PDO)

41. PLGA-fleece (darts) [NS]

42. PLLA

43. PLLA (NS) [electrospinning]

44. PLLA (RESOMERL207S)

45. PLLA; PLGA(L); PLGA(H); PLA/CL; PDLA

46. PLLA; PGA; PLGA; PLAO3

47. Poly(1,8-octanediol citrate)

48. Poly(2-acrylamido-2-methyl-1-propanesulfonic acid (NaAMPS)-co-N,N-dimethylacrylamide(DMAAm))

49. Poly(2-hydroxyethyl methacrylate)

50. Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)

51. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB4HB)

52. Poly(ethyl acrylate-co-hydroxyethyl acrylate) [P(EA-co-HEA)]

53. Poly(ethylene oxide) dimethacrylate (PEODM)

54. Poly(ethylene terephthalate) (PET)

55. Poly(glycerol sebacate) (PGS)

56. Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)

57. Poly(lactic-glycolic acid) (PLGA)

58. Poly(L-lactide-co-e-caprolactone) (PLCL) (NS) [supercritical fluid foaming; solvent-casting and salt leaching method]

59. Poly(L-lactide-co-e-caprolactone) (PLCL) {sponge} [supercritical fluid foaming; solvent-casting and salt leaching method]

60. Poly(L-lactide-co-e-caprolactone) (PLCL); articular cartilage explant (control)

61. Poly(N-isopropylacrylamide)-g-methylcellulose (PNIPAAm-g-MC) thermoreversible hydrogel

62. Poly(N-isopropylacrylamide-co-acrylic acid) (p(NiPAAm-co-AAc)) (hydrogel) [NS]

63. Poly(N-isopropylacryl-amide-co-acrylic acid) thermoreversible gel

64. Poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)]; {agarose}; {alginate}

65. Poly(urethane urea) Artelon®

66. Poly(γ-benzyl-L-glutamate) (PBLG)

67. Poly(ε-caprolactone) (PCL) nanofibrous electrospinning

68. Poly3-hydroxybutyrate4-hydroxybutyrate (P34HB)

69. Polycaprolactone; poly(L-lactide); poly(lactic-co-glycolic acid); polyurethane

70. Polydimethylsiloxane (PDMS)

71. Polydimethylsiloxane (PDMS) concave microwells

72. Polyester poly(3-hydroxybutyrate) (PHB) film

73. Polyethylene glycol diacrylate

74. Polyglycolic acid (PGA)

75. Polyglycolic acid (PGA); cartilage explant

76. Polyglycolic acid (PGA); poly(glycolic acid-e-caprolactone) (PGCL); poly(l-lactic acid-glycolic acid) (PLGA), poly(l-lactic acid-e-caprolactone;75:25 (w/w)) [P(LA-CL)25]; poly-e-caprolactone (tetrabutoxy titanium) [PCL(Ti)]; fullerene C-60 dimalonic acid (DMA)

77. PolyHIPE polymer (PHP)

78. Polyhydroxyalkanoate (PHA) = poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxy-10-38 undecenoate] (PHBU)

79. Poly-L,D-lactic acid (PLDLA)

80. Polylactic acid (PLA); Acrylonitrile butadiene styrene (ABS) (NS) [3D printing]

81. Polylactic acid poly-e-caprolactone (PLCL)

82. Polylactic acid-polyglycolic acid (PLGA)

83. Polylactic glycolic acid (PLGA)

84. Polylactic glycolic acid (PLGA)

85. “Polylactic glycolic

86. acid (3D-PLGA) (NS) [NS]”

87. Polylactide-polyglycolic acid (PLGA)

88. Polylactide-co-glycolide (PLGA) 85:15 microspheres/biodegradable hydrogel

89. Poly-L-lactic acid (PLLA)

90. Poly-L-lactic acid (PLLA) microsphere; poly-L-lactic acid (PLLA) microsphere + tripeptide Arg-Gly-Asp

91. Polymer solutions of poly(ethylene) oxide diacrylate

92. Polyurethane

93. Polyurethane (PU); poly(L/DL-lactide) (PLA)-control

94. Polyurethane/poly(L-lactide-co-D, llactide) (PU/PLDL) [6:4; 5:5; 8:2]

95. Poly-ε-caprolactone (NS) [electrospinning]

96. PuraMatrix (hydrogel) [NS]

97. PVA

98. Recombinant streptococcal collagen-like 2 (Scl2) protein with heparin-binding, integrin-binding and hyaluronic acid-binding peptide sequences (HIHA) [nonviral bacteria]. ScrMMP7-HIHA-Scl2, MMP7-HIHAScl2, MMP7:ACAN(75:25)-HIHA-Scl2, MMP7:ACAN(50:50)-HIHAScl2, MMP7:ACAN(25:75)-HIHA-Scl2 and ACAN-HIHA-Scl2 hydrogels.

99. Self-assembling peptide (KLD) AcN-(KLDL)3-CNH2

100. Self-assembling peptide (KLD); cartilage explants

101. Self-assembling peptide (KLDL)

102. Self-assembling peptide (RADA)4

103. Self-assembling peptide AcN–(KLDL)3–CNH2 hydrogels;{agarose}

104. Self-assembly aggrecan (0.6% w/w), aggrecan–HA (0.6% w/w) and HA (1% w/w) solutions; ~type II collagen/aggrecan; ~PVA hydrogel

105. Silanised hydroxypropyl methylcellulose (Si-HPMC) hydrogel [E4M®]

106. Silated hydroxypropyl methylcellulose (hydrogel) [NS]

107. Silk; collagen; gelatin

108. Silk-elastin-like-protein polymer SELP-47 K

109. Sodium cellulose sulphate; polydiallyl dimethyl ammonium chloride (NS) [NS]

110. Tantalum

111. Tetramethacrylate prepolymer

112. Thermoreversible gelation polymer [poly(N-isopropylacrylamide-co-n-butyl methacrylate) (poly(NIPAAm-co-BMA))]

113. Titanium

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Sha’ban, M., Ahmad Radzi, M.A. (2020). Scaffolds for Cartilage Regeneration: To Use or Not to Use?. In: Chun, H.J., Reis, R.L., Motta, A., Khang, G. (eds) Bioinspired Biomaterials. Advances in Experimental Medicine and Biology, vol 1249 . Springer, Singapore. https://doi.org/10.1007/978-981-15-3258-0_7

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