Nadr Jomha

• University of Alberta

An improved understanding of contact mechanics in the ankle joint is paramount for implant design and ankle disorder treatment. However, existing models generally simplify the ankle joint as a revolute joint that cannot predict contact characteristics. The current study aimed to develop a novel musculoskeletal ankle joint model that can predict con...

Total talus replacement is a promising alternative treatment for talus fractures complicated by avascular necrosis and collapse. This surgical option replaces the human talus bone with a customized talus implant and can maintain ankle joint functionality compared to traditional treatment (e.g., ankle fusion). However, the customized implant is cost...

Objective Vitrification of articular cartilage (AC) is a promising technique which may enable long-term tissue banking of AC allografts. We previously developed a 2-step, dual-temperature, multi-cryoprotectant agent (CPA) loading protocol to cryopreserve particulated AC (1 mm³ cubes). Furthermore, we also determined that the inclusion of ascorbic a...

The common practice of freezing meniscal allograft tissue is limited due to the formation of damaging ice crystals. Vitrification, which eliminates the formation of damaging ice crystals, may allow the mechanical properties of meniscal allograft tissue to be maintained during storage and long-term preservation. The primary objective of this study w...

Cryopreserving articular cartilage by vitrification can increase the availability of tissue for osteochondral allograft transplantation to treat cartilage defects. Developing well-optimized vitrification protocols can be supported by mathematical modeling to reduce the amount of trial-and-error experimentation needed. Fick's law has been used to mo...

Background The use of particulated articular cartilage for repairing cartilage defects has been well established, but its use is currently limited by the availability and short shelf life of donor cartilage. Vitrification is an ice-free cryopreservation technology at ultralow temperatures for tissue banking. An optimized vitrification protocol has...

Articular cartilage (AC) injuries do not heal primarily and large lesions progress to degenerative osteoarthritis. Osteochondral allograft transplantation is an effective surgical treatment but is limited by the lack of donor tissue availability. Fresh allografts can be stored hypothermically up to 28-45 days after which the tissue is no longer via...

Vitrification can extend the banking life of articular cartilage (AC) and improve osteochondral transplantation success. Current vitrification protocols require optimization to enable them to be implemented in clinical practice. Sucrose as a non-permeating cryoprotective agent (CPA) and clinical grade chondroitin sulfate (CS) and ascorbic acid (AA)...

Vitrification inhibits crystallization of ice and may allow the mechanical properties of menisci to be preserved for transplantation without the damaging consequences of ice crystals formed during freezing. The primary objective of this study was to investigate the differences between fresh, frozen, and vitrified porcine lateral menisci examining t...

Cryopreservation of articular cartilage will increase tissue availability for osteochondral allografting and improve clinical outcomes. However, successful cryopreservation of articular cartilage requires the precise determination of cryoprotectant permeation kinetics to develop effective vitrification protocols. To date, permeation kinetics of the...

Osteochondral allografts are often used to repair large articular cartilage defects to prevent or delay the onset of osteoarthritis. This approach is limited by the timely acquisition and use of allograft tissue since standard hypothermic protocols allow for a maximum storage of 4 weeks. Vitrification is a proven technique for the long-term preserv...

Preserving viable articular cartilage is a promising approach to address the shortage of graft tissue and enable the clinical repair of articular cartilage defects in articulating joints, such as the knee, ankle, and hip. In this study, we developed two 2-step, dual-temperature, multicryoprotectant loading protocols to cryopreserve particulated art...

High concentrations of cryoprotective agents (CPAs) are required to achieve successful vitrification of articular cartilage; however, CPA cytotoxicity causes chondrocyte death. To reduce CPA toxicity, supplementation with research-grade additives, in particular chondroitin sulfate (CS) and ascorbic acid (AA), have previously been shown to improve c...

Statistical data pertaining to anatomic variations of the human talus contain valuable information for advances in biological anthropology, diagnosis of the talar pathologies, and designing talar prostheses. A statistical shape model (SSM) can be a powerful data analysis tool for the anatomic variations of the talus. The main concern in constructin...

Meniscus fibrochondrocytes (MFCs) experience simultaneous hypoxia and mechanical loading in the knee joint. Experimental conditions based on these aspects of the native MFC environment may have promising applications in human meniscus tissue engineering. We hypothesized that in vitro “mechano-hypoxia conditioning” with mechanical loading such as dy...

Objective Articular cartilage of the knee joint is avascular, exists under a low oxygen tension microenvironment, and does not self-heal when injured. Human infrapatellar fat pad-sourced mesenchymal stem cells (IFP-MSC) are an arthroscopically accessible source of mesenchymal stem cells (MSC) for the repair of articular cartilage defects. Human IFP...

»: The blood supply to the talus is vulnerable to damage, making the talus susceptible to osteonecrosis, with limited treatment options. »: Talar bone replacement has been investigated as a treatment option to preserve ankle function and maintain limb length. »: Successful talar bone replacements have been performed for the past >35 years, wit...

Adult human meniscus fibrocartilage is avascular and non‐healing after injury. Meniscus tissue engineering aims to replace injured meniscus with lab grown fibrocartilage. Dynamic culture systems may be necessary to generate fibrocartilage of sufficient mechanical properties for implantation; however, the optimal static pre‐culture conditions prior...

[This corrects the article DOI: 10.1371/journal.pone.0248292.].

Low oxygen and mechanical loading may play roles in regulating the fibrocartilaginous phenotype of the human inner meniscus, but their combination in engineered tissues remains unstudied. Here, we investigated how continuous low oxygen (“hypoxia”) combined with dynamic compression would affect the fibrocartilaginous “inner meniscus-like” matrix-for...

This study investigates the transcriptome response of meniscus fibrochondrocytes (MFCs) to the low oxygen and mechanical loading signals experienced in the knee joint using a model system. We hypothesized that short term exposure to the combined treatment would promote a matrix-forming phenotype supportive of inner meniscus tissue formation. Human...

Quantification of the amount of cryoprotective agent (CPA) in a tissue is an essential step in the design of successful cryopreservation protocols. This chapter details two inexpensive methods to measure cryoprotective agent permeation into tissues as functions of time. One of the methods to measure the CPA permeation is to permeate a series of tis...

Objective Successful preservation of articular cartilage will increase the availability of osteochondral allografts to treat articular cartilage defects. We compared the effects of 2 methods for storing cartilage tissues using 10-mm diameter osteochondral dowels or femoral condyles at −196°C: (a) storage with a surrounding vitrification solution ve...

Objective: Bone marrow–derived mesenchymal stem cells (BMSCs) have the potential to form the mechanically responsive matrices of joint tissues including the menisci of the knee joint. The purpose of this study is to assess BMSC’s potential to engineer meniscus-like tissue relative to meniscus fibrochondrocytes (MFC). Methods: MFC were isolated from...

Vitrification of mammalian tissues is important in the areas of human assisted reproduction, animal reproduction, and regenerative medicine. Non-permeating cryoprotectants (CPAs), particularly sucrose, are increasingly used in conjunction with permeating CPAs for vitrification of mammalian tissues. Combining non-permeating and permeating CPAs was f...

Due to the complexity of articular interconnections and tenuous blood supply to the talus, talus fractures are often associated with complications (e.g., avascular necrosis). Currently, surgically fusing the talus to adjacent bones is widely used as treatment to talus fractures, but this procedure can greatly reduce mobility in the ankle and hindfo...

Osteochondral allograft transplantation can treat full thickness cartilage and bone lesions in the knee and other joints, but the lack of widespread articular cartilage banking limits the quantity of cartilage available for size and contour matching. To address the limited availability of cartilage, vitrification can be used to store harvested join...

Vitrification is a cryopreservation technique for the long-term storage of viable tissue, but the success of this technique relies on multiple factors. In 2012, our group published a working vitrification protocol for intact human articular cartilage and reported promising chondrocyte recovery after using a four-step multi-cryoprotectant (CPA) load...

Talar avascular necrosis (AVN) can result in bone collapse with subsequent ankle and subtalar osteoarthritis ending in significant pain and disability. Custom talar body prostheses have been implanted with good results but these are difficult to design, costly and require extensive planning. In the past few years, we have investigated the feasibili...

INTRODUCTION: The biomechanically active inner meniscus is non-healing in adults and contains a matrix rich in collagens I and II and sulphated proteoglycans. The direct comparison between meniscus fibrochondrocytes (MFCs) and bone marrow mesenchymal stem cells (BMSCs) for engineering replacement inner meniscus tissue has been previously investigat...

Traumatic injury and idiopathic avascular necrosis of the talus bone can result in osteochondral lesions of the talus leading to pain, motion loss, and disability. Treatment with osteochondral allografting currently requires the donor talus to be size matched to the recipient talus to ensure precise fits. Eliminating or reducing the need for size m...

Cryoprotective agents (CPAs) are used in cryopreservation protocols to achieve vitrification. However, the high CPA concentrations required to vitrify a tissue such as articular cartilage are a major drawback due to their cellular toxicity. Oxidation is one factor related to CPA toxicity to cells and tissues. Addition of antioxidants has proven to...

Impact statement: The interactions of hypoxia and TGF-β3 in aggregates of human meniscus fibrochondrocytes are synergistic in nature, suggesting combinatorial strategies using these factors are promising for tissue engineering the inner meniscus regions. Hypoxia alone in the absence of TGF-β supplementation may be insufficient to initiate an inner...

The objective of this study was to investigate whether meniscus-derived decellularized matrix (DCM) has the capacity to induce differentiation of synovial fluid-derived mesenchymal stem cells (SF-MSCs) towards a meniscus fibrochondrocyte (MFC) phenotype. The potential roles of transforming growth factor beta-3 (TGF-β3) and insulin-like growth facto...

Treatment for talar avascular necrosis is challenging. This study evaluates the feasibility of a generic talar implant by cadaveric assessment. Ten cadaveric ankles were CT-scanned to determine talar implant size. The opposite ankles were CT-scanned with the biological talus and then with the implant. 3D ankle geometry was reconstructed and implant...

Cartilage: Simulated microgravity promotes cartilage matrix deposition Co-culture of meniscal cartilage-forming cells with fat-derived stem cells can lead to enhanced cartilage matrix production when cultured under simulated microgravity. Adetola Adesida from the University of Alberta in Edmonton, Canada, and colleagues cultured two types of cells...

Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects. The objective of this study was to assess a protocol that involved autologous transplantation of BMSCs into full-thickness cartilage defects in sheep following isolation, expansion and a short period (4 days) of chondroge...

Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects. Quality of cartilaginous repair tissue following BMSC transplantation has been shown to correlate with functional outcome in a clinical setting. Therefore, tissue engineering and transplantation variables are currently un...

Meniscus fibrochondrocytes (MFCs) may be the optimal cell source to repair non-healing meniscus injuries using tissue engineering strategies. In this study, we investigated the effects of mitotic divisions and oxygen tension on the plasticity of adult human MFCs. Our assessment techniques included gene expression, biochemical, histological, and imm...

The menisci distribute loads to protect the articular cartilage of the knee joint from excessive stress. Injuries to their avascular inner regions do not heal, disrupt function, and increase the risk for knee osteoarthritis. Meniscus tissue engineering aims to restore normal meniscus function by use of regenerated tissue on bioengineered scaffolds....

Background: A talar body prosthetic implant may be indicated after a severe fracture in the talus bone resulting in avascular necrosis with collapse. This process is patient-specific, in which the geometry is copied from the healthy talus of the opposite foot to create the implant. More recently, an ‘off-the-shelf’ non-custom talar prosthetic was p...

High concentrations of cryoprotective agents are required for cryopreservation techniques such as vitrification. Glycerol is a common cryoprotective agent used in cryopreservation protocols but this agent is toxic at high concentrations. This work is an attempt to mitigate the toxic effects of high concentrations of glycerol on intact chondrocytes...

Background Trauma to the talus can result in fracture, avascular necrosis and structural collapse. Treatment has been limited to surgical fusion and total ankle arthroplasty. Total ankle arthroplasty may not be an appropriate treatment for avascular necrosis while surgical fusion of the joint limits mobility. Custom-made implants have recently been...

Background Animal models are commonly used in investigating new treatment options for knee joint injuries including injuries to the meniscus. The reliability and applicability of these models to replicate findings in humans depends on determining the most suitable animal proxy. Therefore, this study was designed to compare the wet weight, volume an...

The development of a long-term storage method for meniscus, a complex tissue of the knee prone to injury, would improve the procedure and outcomes of meniscus transplantation. Cryopreservation uses cryoprotective agents (CPAs) including ethylene glycol (EG) and glycerol to preserve a variety of live tissues, and understanding of the CPA permeation...

Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects. Quality of cartilaginous repair tissue following BMSC transplantation has been shown to correlate with functional outcome. Therefore, tissue-engineering variables, such as cell expansion environment and seeding density of...

Purpose: This preclinical pilot study assessed a novel protocol that involved transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) into full-thickness cartilage defects in sheep following isolation, expansion and a short period (4 days) of chondrogenic priming. The impact of oxygen tension during pre-implantation culture was invest...

We recently published a protocol to vitrify human articular cartilage and a method of cryoprotectant removal in preparation for transplantation. The current study's goal was to perform a cryoprotectant kinetic analysis and theoretically shorten the procedure used to vitrify human articular cartilage. First, the loading of the cryoprotectants was mo...

Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects. BMSCs have conventionally been isolated by plastic adherence and expanded in a two-dimensional (2D) environment within tissue-culture flasks [1]. Although this method has been shown to produce cells capable of chondrogeni...

Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects (Bornes et al., 2014). BMSCs can be seeded within porous biomaterial scaffolds that support three-dimensional cell organization, chondrogenic differentiation and extracellular matrix deposition for the creation of engineer...

Introduction Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects. The objective of this study was to assess the impact of cell seeding density within a collagen I scaffold on in vitro BMSC chondrogenesis following isolation and expansion in two-dimensional (2D) and three-di...

Chondral and osteochondral fractures of the lower extremities are important injuries because they can cause pain and dysfunction and often lead to osteoarthritis. These injuries can be misdiagnosed initially which may impact on the healing potential and result in poor long-term outcome. This comprehensive review focuses on current pitfalls in diagn...

Toxicity plays a central role in cryopreservation, whether it be toxicity of added cryoprotectants or of naturally occurring salts and other solutes concentrated in the unfrozen solution by ice formation. Toxicity may be studied from the viewpoint of biochemical mechanisms—understanding what molecule, pathway, or structure is “poisoned”. However, a...

Knee dislocation with a common peroneal nerve injury is a serious problem. A case of multi-ligamentous knee injury with the unusual and interesting finding of a common peroneal nerve rupture incarcerated within the knee joint is presented. MRI and arthroscopic images are used to document this occurrence. To date, there are no published reports of a...

Purpose: Hypoxic culture of bone marrow mesenchymal stem cells (BMSCs) has been shown to enhance hyaline-like cartilage formation within in vitro pellet, micromass and hydrogel models, although this effect has not been elucidated in detail within porous scaffolds. The objective of this study was to assess the effect of hypoxia on in vitro chondroge...

The menisci are a pair of semilunar fibrocartilage structures that play an essential role in maintaining normal knee function. Injury to the menisci can disrupt joint stability and lead to debilitating results. Because natural meniscal healing is limited, an efficient method of repair is necessary. Tissue engineering (TE) combines the principles of...

Quality of cartilaginous tissue derived from bone marrow mesenchymal stromal stem cell (BMSC) transplantation has been correlated with clinical outcome. Therefore, culture conditions capable of modulating tissue phenotype, such as oxygen tension and scaffold composition, are under investigation. The objective of this study was to assess the effect...

The transplantation of bone-bearing living articular cartilage is an effective treatment for joint injury and disease. Widespread access to this treatment, however, will require the ability to cryopreserve and bank this tissue. The cryopreservation of articular cartilage has been studied for more than 50 years, with early unsuccessful attempts at f...

Articular cartilage has a limited capacity to repair following injury. Early intervention is required to prevent progression of focal traumatic chondral and osteochondral defects to advanced cartilage degeneration and osteoarthritis. Novel cell-based tissue engineering techniques have been proposed with the goal of resurfacing defects with bioengin...

Open fractures are a common problem encountered by orthopaedic surgeons and comprise a broad spectrum of trauma. Management is guided by principle-based steps aimed at reducing the risk of gas gangrene or suppurative infections, whilst maintaining viability in a favourable soft tissue environment to reduce the risk of delayed or non-union of bone....

The main object of this study was to use a geometric morphometric approach to quantify the left-right symmetry of talus bones. Analysis was carried out using CT scan images of 11 pairs of intact tali. Two important geometric parameters, volume and surface area, were quantified for left and right talus bones. The geometric shape variations between t...

Proper understanding of the complex geometric shape of the talus bone is important for the design of generic talar body prosthetics and restoration of the proper ankle joint function after surgery. To date, all talus implants have been patient-specific with the limitation that complex computer modeling is required to produce a mirrored image from t...

Limited intrinsic healing potential of the meniscus and a strong correlation between meniscal injury and osteoarthritis have prompted investigation of surgical repair options, including the implantation of functional bioengineered constructs. Cell-based constructs appear promising, however the generation of meniscal constructs is complicated by the...

The ultimate aim of this study was to assess the feasibility of using human bone marrow stromal cells (BMSCs) to supplement meniscus cells for meniscus tissue engineering and regeneration. Human menisci were harvested from three patients undergoing total knee replacements. Meniscus cells were released from the menisci after collagenase treatment. B...

Vitrification of articular cartilage (AC) could enhance tissue availability but requires high concentrations of cyroprotective agents (CPAs). This study investigated relative injuries caused by commonly used CPAs. We hypothesized that the in situ chondrocyte dose-injury relationships of five commonly used CPAs are nonlinear and that relative injuri...

Previous studies showed that co-culture of human meniscus cells (MCs) and bone marrow mesenchymal stromal cells (BMSCs) result in enhanced production of functional matrix of meniscus relative to mono-cultured MCs and BMSCs. To consider the combination of MCs and BMSCs as a cell source to generate functional grafts to aid meniscus repair or as a men...

Cryopreservation has numerous practical applications in medicine, biotechnology, agriculture, forestry, aquaculture and biodiversity conservation, with huge potentials for biological cell and tissue banking. A specific tissue of interest for cryopreservation is the articular cartilage of the human knee joint for two major reasons: (1) clinically, t...

In previous research, we successfully cryopreserved intact human articular cartilage on its bone base with high chondrocyte viability using a vitrification protocol that entailed sequential exposure to several cryopreserving agents (CPAs) at lowering temperatures resulting in a high final concentration of CPA. The CPA must be removed from the carti...

The main objective of this study was to determine whether meniscus cells from the outer (MCO) and inner (MCI) regions of the meniscus interact similarly to or differently with mesenchymal stromal stem cells (MSCs). Previous study had shown that co-culture of meniscus cells with bone marrow-derived MSCs result in enhanced matrix formation relative t...

BACKGROUND: Meniscal cartilage displays a poor repair capacity, especially when injury is located in the avascular region of the tissue. Cell-based tissue engineering strategies to generate functional meniscus substitutes is a promising approach to treat meniscus injuries. Meniscus fibrochondrocytes (MFC) can be used in this approach. However, MFC...

Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunct...

The capacity of bone marrow mesenchymal stromal cells (BMSCs) to be induced into chondrocytes has drawn much attention for cell-based cartilage repair. BMSCs represent a small proportion of cells of the bone marrow stromal compartment and, thus, culture expansion is a necessity for therapeutic use. However, there is no consensus on how BMSCs should...