polymers Review Articular and Artificial Cartilage, Characteristics, Properties and Testing Approaches—A Review Mohammad Mostakhdemin 1,*, Ashveen Nand 2,3 and Maziar Ramezani 1,* 1 Department of Mechanical Engineering, Auckland University of Technology, Auckland 1142, New Zealand 2 School of Environmental and Animal Sciences, Unitec Institute of Technology, Auckland 1025, New Zealand; [email protected] 3 School of Healthcare and Social Practice, Unitec Institute of Technology, Auckland 1025, New Zealand * Correspondence: [email protected] (M.M.); [email protected] (M.R.) Abstract: The design and manufacture of artificial tissue for knee joints have been highlighted recently among researchers which necessitates an apt approach for its assessment. Even though most re-searches have focused on specific mechanical or tribological tests, other aspects have remained underexplored. In this review, elemental keys for design and testing artificial cartilage are dis-cussed and advanced methods addressed. Articular cartilage structure, its compositions in load-bearing and tribological properties of hydrogels, mechanical properties, test approaches and wear mechanisms are discussed. Bilayer hydrogels as a niche in tissue artificialization are presented, and recent gaps are assessed. Keywords: articular cartilage; hydrogels; mechanical properties; tribological properties Citation: Mostakhdemin, M.; Nand, A.; Ramezani, M. Articular and 1. Introduction Artificial Cartilage, Characteristics, The complex structure of healthy articular cartilage facilitates the joint withstanding Properties and Testing Approaches the imposed pressures and retaining interstitial fluid to lessen stresses on its soft tissue —A Review. Polymers 2021, 13, 2000. while easing the locomotion and minimizing friction between cartilage mates. Avascular https://doi.org/10.3390/ nature of this tissue results in unrecoverable damaged lesions and severe pain over time. polym13122000 Polymeric hydrogels are promising candidate materials for the replacement of the damaged cartilage. Moreover, polymeric scaffolds have been applied in interface tissue engineering Academic Editor: Bramasta Nugraha and their uses have extended to bone to tendon and muscle to tendon interface recon- struction [1]. Recently, bilayer hydrogels have been developed with distinct techniques Received: 19 May 2021 as promising artificial cartilage due to their resemblance to the native cartilage structure. Accepted: 14 June 2021 Bilayer hydrogels contain bulk and lubricious layers that enhance water retention in their Published: 18 June 2021 lubricious layer and advance tribological properties such as wear-resistance and coefficient of friction (CoF). The absence of optimum mechanical and tribological properties has been Publisher’s Note: MDPI stays neutral highlighted as a research gap in recent years because promoting mechanical properties with regard to jurisdictional claims in published maps and institutional affil- results in a reduction in the tribological properties or vice versa. iations. In this study, summaries of recent research are covered, also essential elements in designing of artificial cartilage, common materials, required tests according to standard regulations and strengthening method are discussed broadly. Recent research has been highlighted and gaps addressed adequately. This review further discusses the fundamental resources that are considered in design of wide ranges of hydrogels specially bilayer Copyright: © 2021 by the authors. hydrogels which have gained researchers’ attention due to their promising mechanical and Licensee MDPI, Basel, Switzerland. tribological properties. This article is an open access article distributed under the terms and 2. Synovial Joints conditions of the Creative Commons Attribution (CC BY) license (https:// Synovial joints, being the most common joints in mammals, are characterized by creativecommons.org/licenses/by/ allowing movement in multiple planes. They allow for the articulation of long bones, 4.0/). ends of which are covered with articular cartilage (AC), within a fluid-filled cavity. AC, Polymers 2021, 13, 2000. https://doi.org/10.3390/polym13122000 https://www.mdpi.com/journal/polymers Polymers 2021, 13, x FOR PEER REVIEW 2 of 25 2. Synovial Joints Synovial joints, being the most common joints in mammals, are characterized by al- lowing movement in multiple planes. They allow for the articulation of long bones, ends of which are covered with articular cartilage (AC), within a fluid-filled cavity. AC, incor- Polymers 2021, 13, 2000 2 of 25 porated with a viscous synovial fluid, is a biphasic tissue that provides extremely low friction [2]. It mitigates overstressing on the tissue’s solid phase, while dissipating energy and enabling smooth joints movements. The synovial fluid consists of hyaluronic acid incorporated with a viscous synovial fluid, is a biphasic tissue that provides extremely low (HA), glycosaminoglycans (GAGs) containing chondroitin-4-sulfate, chondroitin-6-sul- friction [2]. It mitigates overstressing on the tissue’s solid phase, while dissipating energy fate,and keratan enabling sulfate smooth and joints mobile movements. ions and The is a synovial dialysate fluid of blood consists plasma of hyaluronic without acid hemoglo- bin(HA), [3]. glycosaminoglycans The synovial fluid (GAGs) is contained containing mainly chondroitin-4-sulfate, within the molecular chondroitin-6-sulfate, pore spaces of the cartilagekeratan sulfate cells [4]. and AC mobile incorporates ions and is athe dialysate viscous of synovial blood plasma fluid without to mitigate hemoglobin shock-loadings [3]. initiatedThe synovial by physiological fluid is contained activities mainly and within body the weight molecular [5]. Hence, pore spaces AC supports of the cartilage smooth joint movementscells [4]. AC at incorporates an extremely the viscous low coefficient synovial fluid of friction to mitigate (CoF) shock-loadings [6]. initiated by physiological activities and body weight [5]. Hence, AC supports smooth joint movements 3.at The an extremely Structure low of coefficientArticular ofCartilage friction (CoF) [6]. 3. TheThe Structure AC structure of Articular is complex, Cartilage as the compositions of GAGs, chondrocytes and colla- gen areThe in AC random structure orientations is complex, and as the densities; compositions with of the GAGs, main chondrocytes components and of collagen this composi- tionare incontains random water orientations (60–85%), and collagen densities; type with II the (15–22%) main components and Proteoglycan of this composition (PG) (4–7%) [7]. Itscontains deep zone water includes (60–85%), hydroxyapatite collagen type II (Hap) (15–22%) combined and Proteoglycan with collagen (PG) (4–7%)and chondrocyte [7]. Its in thedeep vertical zone includes orientation hydroxyapatite [8], as illustrated (Hap) combined in Figure with 1. AC collagen is a biphasic and chondrocyte substrate in categorized the asvertical a nonlinear, orientation anisotropic, [8], as illustrated viscoelastic in Figure and1 .inhomogeneous AC is a biphasic substrate material categorized [7,9]. as a nonlinear, anisotropic, viscoelastic and inhomogeneous material [7,9]. FigureFigure 1. 1. IllustrationIllustration of of the the AC AC structure: structure: superficial,superficial, transition transition and and deep deep zones. zones. Reproduced Reproduced from [10].from [10]. Zonal Categories of Articular Cartilage ZonalAC Categories is a soft of avascular Articular tissue Cartilage with a 3–4 mm thickness and integrates three depth- dependentAC is a layers soft ofavascular superficial, tissue transition with anda 3–4 deep mm zones. thickness Each layerand integrates is responsible three for depth- dependentminimizing layers either theof superficial, imposing load transition or friction an ofd thedeep sliding zones. movement, Each layer as described is responsible in for minimizingthe following either sections. the imposing load or friction of the sliding movement, as described in the followingThe top layer sections. (superficial zone) contains collagen fibrils cells in the horizontal orien- tation, which confers high tensile stiffness and strength. This layer is just 10–20% of the The top layer (superficial zone) contains collagen fibrils cells in the horizontal orien- tissue’s thickness [11]; both fibrils and chondrocytes are stretched along their length and sur- tation,rounded which at the confers surface withhigh the tensile finest stiffness size compared and strength. to the other This layers’ layer chondrocytes is just 10–20% [12]. of the tissue’sThis feature thickness also custodies [11]; both the fibrils tissue and against chondr highocytes tensile stressesare stretched and prevents along interstitialtheir length and surroundedfluid permeation, at the which surface plays with a vital the rolefinest in slidingsize compared on cartilage to the surface other mates layers’ [13]. chondrocytes While [12].this This layer feature has high also water custodies content, the it has tissue the lowestagainst PG high [14 ].tensile The superficial stresses and zone prevents is also inter- stitialcalled fluid the surface permeation, amorphous which layer plays (SAL) a vital that role is acellular in sliding with on no cartilage fibril content surface [7]. mates Its [13]. Whilethickness this is layer a few has micrometers, high water containing content, proteins,it has the glycoproteins, lowest PG [14]. PGs, The hyaluronic superficial acid- zone is alsoprotein called complexes,