Osteochondral tissue repair in osteoarthritic joints: clinical challenges and opportunities in tissue engineering

Osteoarthritis (OA), identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA usually stems from repetitive overloading to the osteochondral (OC) unit, which could result in cartilage damage and changes in the subchondral bone, leading to mechanical instability of the joint and loss of joint function. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bone in the early stages of OA and have shown potential in restoring the joint’s function. In this approach, the use of three-dimensional scaffolds (with or without cells) provides support for tissue growth. Commercially available OC scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, none of these scaffolds has shown satisfactory clinical results. This article reviews the OC tissue structure and the design, manufacturing and performance of current OC scaffolds in treatment of OA. The findings demonstrate the importance of biological and biomechanical fixations of OC scaffolds to the host tissue in achieving an improved cartilage fill and a hyaline-like tissue formation. Achieving a strong and stable subchondral bone support that helps the regeneration of overlying cartilage seems to be still a grand challenge for the early treatment of OA

Simulation of the flow and the study of the effects of the surface roughness in isothermal gas flows of micro scale using Lattice Boltzmann method

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this paper, a lattice Boltzmann method used in the simulation of the fluid flow in micro/nano scale is introduced and studied. The method can be employed instead of NS equations in cases where the continuum assumption is no longer valid. In the present study the aim is to investigate the effects of surface roughness on flow characteristics of micro/nano gas flows. In order to compare the final results, two flow geometries were chosen for which the numerical and experimental results were available. Surface roughness was increased in each stage (from completely smooth to 12% roughness) and its influences on the flow regime, pressure and velocity distribution, slip velocity and mass flow rate were studied. It is shown that surface roughness results in a decrease in the mass flow rate as well as slip velocity. Increasing the amount of roughness causes the mass flow rate to continually decrease, however this trend is inverted for the slip velocity

Micro-Computed Tomography Analysis of Subchondral Bone Regeneration Using Osteochondral Scaffolds in an Ovine Condyle Model

Osteochondral scaffold technology has emerged as a promising therapy for repairing osteochondral defects. Recent research suggests that seeding osteochondral scaffolds with bone marrow concentrate (BMC) may enhance tissue regeneration. To examine this hypothesis, this study examined subchondral bone regeneration in scaffolds with and without BMC. Ovine stifle condyle models were used for the in vivo study. Two scaffold systems (8 mm diameter and 10 mm thick) with and without BMC were implanted into the femoral condyle, and the tissues were retrieved after six months. The retrieved femoral condyles (with scaffold in) were examined using micro-computed tomography scans (micro-CT), and the micro-CT data were further analysed by ImageJ with respect to trabecular thickness, bone volume to total volume ratio (BV/TV) ratio, and degree of anisotropy of bone. Statistical analysis compared bone regeneration between scaffold groups and sub-set regions. These results were mostly insignificant (p < 0.05), with the exception of bone volume to total volume ratio when comparing scaffold composition and sub-set region. Additional trends in the data were observed. These results suggest that the scaffold composition and addition of BMC did not significantly affect bone regeneration in osteochondral defects after six months. However, this research provides data which may guide the development of future treatments

Polymerization of chondroitin sulfate and its stimulatory effect on cartilage regeneration; a bioactive material for cartilage regeneration

Chondroitin sulfate (CS) is one of the major glycosaminoglycans (GAGs). GAGs are linear polymers comprising disaccharide residues and are found as the side chains of proteoglycans. CS has significant stimulatory effects on cell behavior and is widely used in tissue-engineered and drug delivery devices. However, it is difficult to incorporate a sufficient amount of CS into biopolymer-based scaffolds such as collagen to take full advantage of its benefit. In this study, CS has been polymerized to an 11 times higher molecular weight polymer (PCS) in an attempt to overcome this deficiency. We have previously shown that PCS was significantly more effective than CS in chondrogenesis. This study aimed to characterize the physicochemical properties of the manufactured PCS. PCS was characterized by Fourier transform infra-red (FTIR) spectroscopy together with X-ray photoelectron spectroscopy (XPS) to obtain information about its chemical structure and elemental composition. Its molecular size was measured using dynamic light scattering (DLS) and its viscoelastic properties were determined by rheology measurements. The average PCS diameter increased 5 times by polymerization and PCS has significantly enhanced viscoelastic properties compared to CS. The molecular weight of PCS was calculated from the rheological experiment to give more than an order of magnitude increase over CS molecular weight. Based on these results, we believe there is a great potential for using PCS in regenerative medicine devices

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance

A Bilayer Osteochondral Scaffold with Self‐Assembled Monomeric Collagen Type‐I, Type‐II, and Polymerized Chondroitin Sulfate Promotes Chondrogenic and Osteogenic Differentiation of Mesenchymal Stem Cells

Osteochondral (OC) injuries are suffered by over 40 million patients in Europe alone. Tissue-engineering approaches may provide a more promising alternative over current treatments by potentially eliminating the need for revision surgery and creating a long-term substitute. Herein, the goal is to capture the natural biological and mechanical properties of the joint by developing a bilayer scaffold that is novel in two ways: first, a biomimetic bottom-up approach is used to improve production precision and reduce immunogenicity; monomeric collagen type I and II are self-assembled to fibrils and then processed to 3D scaffolds. Second, to induce a tissue-specific response in mesenchymal stem cells (MSCs), polymerized chondroitin sulfate (PCS) is synthesized and grafted to collagen II and hydroxyapatite (HA) is added to collagen I. Incorporation of PCS into collagen II induces a chondrogenic response by upregulation of COL2A1 and ACAN expression, and incorporation of HA into collagen I stimulates osteogenesis and upregulates the expression of COL1A2 and RUNX2. It is remarkable that MSCs give rise to distinct behavior of chondrogenesis and osteogenesis in the two different regions of the bilayer scaffold. This hybrid scaffold of collagen II-PCS and collagen I-HA offers a great potential treatment for OC injuries

Intrinsic Osteoinductivity of Porous Titanium Scaffold for Bone Tissue Engineering

Large bone defects and nonunions are serious complications that are caused by extensive trauma or tumour. As traditional therapies fail to repair these critical-sized defects, tissue engineering scaffolds can be used to regenerate the damaged tissue. Highly porous titanium scaffolds, produced by selective laser sintering with mechanical properties in range of trabecular bone (compressive strength 35 MPa and modulus 73 MPa), can be used in these orthopaedic applications, if a stable mechanical fixation is provided. Hydroxyapatite coatings are generally considered essential and/or beneficial for bone formation; however, debonding of the coatings is one of the main concerns. We hypothesised that the titanium scaffolds have an intrinsic potential to induce bone formation without the need for a hydroxyapatite coating. In this paper, titanium scaffolds coated with hydroxyapatite using electrochemical method were fabricated and osteoinductivity of coated and noncoated scaffolds was compared in vitro. Alizarin Red quantification confirmed osteogenesis independent of coating. Bone formation and ingrowth into the titanium scaffolds were evaluated in sheep stifle joints. The examinations after 3 months revealed 70% bone ingrowth into the scaffold confirming its osteoinductive capacity. It is shown that the developed titanium scaffold has an intrinsic capacity for bone formation and is a suitable scaffold for bone tissue engineering

Decrease in local volumetric bone mineral density (vBMD) in osteoarthritic joints is associated with the increase in cartilage damage: a pQCT study

Osteoarthritis (OA) is one of the most prevalent joint diseases, which causes pain and disability in the adult population. OA affects the osteochondral unit in the joints, which comprises both cartilage and subchondral bone. There has been some progress in understanding the changes in subchondral bone with progression of OA. However, local changes in subchondral bone such as microstructure or volumetric bone mineral density (vBMD) in connection with the defect in cartilage are relatively unexplored. To develop an effective treatment for progression of OA, it is important to understand how the physical environment provided by the subchondral bone affects the overlying cartilage. In this study, we examined the vBMD distribution in the OA joint tissues obtained from total hip replacement surgeries due to OA, using peripheral quantitative CT (pQCT). It was found that there is a significant decrease in vBMD, which co-localizes with the damage in the overlying cartilage. This was not limited to the subchondral bone immediately adjacent to the cartilage defect but continued in the layers below. Bone resorption and cyst formation in the OA tissues were also detected. We observed that the bone surrounding subchondral bone cysts exhibited much higher vBMD than that of the surrounding bones. pQCT was able to detect significant changes in vBMD between OA and non-OA samples, as well as between areas of different cartilage degeneration, which points to its potential as a technique for detection of early OA