New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

Table 1 Natural and synthetic materials

Natural and synthetic materials	Materials	Advantages
Natural	Natural Silk, collagen, gelatin, fibrinogen, hyaluronic acid, alginate	Biodegradable
		Easily available
		Bioactive, interact with cells
Synthetic	PEG, PGA, PMMA, PLGA	Facilitate restoration of structure of damaged tissues
		Inert
		Long shelf-life
		Easily tailored for desired porosity and degradation time
		Predictable and reproducible mechanical and physical properties

PGA: Polyglycolic acid; PLGA: Poly (lactic-co-glycolic acid); PEG: Polyethylene glycol; PMMA: Polymethyl methacrylate.

Table 2 Overview of advantages and disadvantages of various scaffolds

Scaffold	Advantages	Disadvantages
Porous scaffolds	High porosity	Use of highly toxic solvent
	Interconnected structure	Low pore interconnectivity
	Simple and easy to manufacture	Difficulty in homogenous cell seeding post scaffold fabrication
		Highly porous scaffolds can have weak mechanical properties
		Lack of control over scaffold thickness
Fibrous scaffolds	Fiber meshes and fiber bonding are simple techniques	Fiber meshes lack mechanical integrity
	Large surface area-volume ratio	Fiber bonding lacks control over porosity and pore size
	High inter-fiber distances for nutrition and gas exchange	Small pore sizes produced during fabrication processes such as electrospinning limit cell infiltration and 3-D cellular integration with host tissue after implantation
Hydrogels	Can form stable and highly ordered scaffolds using self assembly
	Tissue like flexibility	Higher cost
	Viscoelasticity	Non-adherent and usually need to be secured by a secondary dressing, for in-vivo testing
Custom scaffolds (Computer-aided design technique)	Intestinal flow and diffusive transport	Natural polymer hydrogels like collagen gelatin, alginate and agarose may evoke inflammatory responses
	Controlled matrix architecture: size, shape, interconnectivity, branching, geometry and orientation	Low resolution of current systems
	Can control pore and pore size	Selective polymeric materials can only be used
	Controlled mechanical properties and degradation kinetics
Microspheres	Reproducible architecture and compositional variations
	Used as cell carriers, when fabricated using biodegradable and non-toxic materials	Difficult to remove once injected or implanted
	Large surface area for cell attachment and growth	Unknown toxicity associated with microsphere/beads
Native/Extracellular matrix scaffolds	Applicable for 3-D cell culture in a stirred suspension bioreactor Simulates the cell's natural microenvironment in terms of composition, bioactive signal and mechanical properties	Difficult to control degree of decellularization and retain all ECM
		Non-uniform distribution of cells
		Immunogenicity upon incomplete decellularization

Table 3 Overview of advantages and disadvantages of various scaffolds

Cells	Material	Results
Chondrocyctes	Poly(epsilon-caprolactone)-block-poly(L-lactide)	Applicable for cartilage tissue engineering
Rabbit marrow mesenchymal stem cells	Oligo(poly(ethylene glycol) fumarate) with encapsulated cells and gelatin microparticles loaded with TGF-β1	Maintained viability of cells for 14 d
		Differentiation of cells into chondrocyte-like cells
Chondrocytes	Gelatin microparticle aggregates, +/- TGF-β1	Supported viability and function of chondrocytes
		Applications in cartilage-engineering
Human adipose derived stem cells	Genipin-crosslinked cartilage derived matrix	Using genipin resulted in contraction free biomaterial.
		Chondrogenesis
Human mesenchmal stem cells	Poly(epsilon-caprolactone)	Cell colonization, proliferation and osteogenic differentiation were related to the micro-architecture of the pore structure
Human chondrocytes	Blend of poly (lactic-co-glycolic acid) and polyvinyl alcohol	Supported cell adhesion and growth
		After implantation, there was better bone in-growth and bone formation inside the scaffold.
Bone marrow stem cells	Polyglycolic acid, poly (lactic acid)	Cell infiltrated the scaffold
		Good cellular compatibility
		Applicable to repair craniomaxillofacial bone defects

TGF: Transforming growth factor.