Stephen D Waldman

Toronto Metropolitan University · Department of Chemical Engineering

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed...

Objective Bisphosphonates are commonly used anti-osteoporotic drugs which have controversial effects on joint diseases including osteoarthritis. Certain bisphosphonates have been shown to have anabolic effects on cartilage which could have important ramifications for their proposed effects in vivo; however, the underlying mechanisms are poorly unde...

Chondrocyte sensitization and desensitization to mechanical stimuli are complex phenomena that have not been fully described. In this study, we investigated the temporal response of chondrocytes to dynamic mechanical loading and whether changes in calcium signaling could be used a predictor of the biosynthetic response. Cell-seeded agarose gels pre...

Joint resurfacing techniques offer an attractive treatment for damaged or diseased cartilage, as this tissue characteristically displays a limited capacity for self-repair. While tissue-engineered cartilage constructs have shown efficacy in repairing focal cartilage defects in animal models, a substantial number of cells are required to generate su...

External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relevatively few surgical approaches are currently available (alloplastic implants or sculpted autolog...

Dynamic mechanical stimulation has been an effective method to improve the growth of tissue engineering cartilage constructs derived from immature cells. However, when more mature cell populations are used, results are often variable due to the differing responses of these cells to external stimuli. This can be especially detrimental in the case of...

Articular cartilage is located at the distal ends of the bones in all articulating joints, providing a gliding surface for the bones to articulate on. It is composed of four major components: collagen, proteoglycans, water and chondrocytes [1–3]. Collagens are fibrillar proteins that provide tensile properties to the cartilage and make the tissue r...

Cell-cell communication plays a critical role in a myriad of processes, such as homeostasis, angiogenesis, and carcinogenesis, in multi-cellular organisms. Monolayer cell models have notably improved our understanding of cellular interactions. However, the cultured cells on the planar surfaces adopt a two-dimensional morphology, which poorly imitat...

Wrinkled surfaces have extraordinary characteristics, such as enlarged surface area and enhanced adhesion, which form the basis of several emerging applications in electrical, mechanical, and biological processes. Furthermore, wrinkles at a nanoscale display additional ultrahigh functions offering enhanced Raman scattering and superhydrophobicity;...

Skeletal fractures, including those resulting from osteoporosis, result in significant healthcare and societal costs on an annual basis. Therefore, it is important to understand the mechanisms by which these fractures occur. Incremental compression testing combined with micro-CT imaging has been used to visualize the progression of failure in trabe...

Objectives: Tissue engineering of auricular cartilage has great potential in providing readily available materials for reconstructive surgeries. As the field of tissue engineering moves forward to developing human tissues, there needs to be an interspecies comparison of the native auricular cartilage in order to determine a suitable animal model t...

In an attempt to combat the possibility of bacterial infection and insufficient bone growth around metallic, surgical implants, bioactive glasses may be employed as coatings. In this work, silica-based and borate-based glass series were synthesized for this purpose and subsequently characterized in terms of antibacterial behavior, solubility and cy...

In this study, zinc borate-based glasses with increasing gallium content (0, 2.5, 5, 10, and 15 wt % Ga) were synthesized and their effect on the viability and proliferation of preosteoblasts and osteosarcoma cancer cells were investigated. Methyl thiazolyl tetrazolium (MTT) cell viability assays using glass degradation extracts revealed that the e...

Low collagen accumulation in the extra-cellular matrix is a pressing problem in cartilage tissue engineering, leading to a low collagen-to-glycosaminoglycan (GAG) ratio and poor mechanical properties in neo-cartilage. Soluble factors have been shown to increase collagen content, but may result in a more pronounced increase in GAG content. Thyroid h...

Articular cartilage is a viscoelastic tissue, which provides a low friction surface for articulating joints (i.e., shoulder, hip, knee, etc.) and allows load transmission to underlying bones. Its strength and viscoelastic properties are determined by the density and structural organization of its extracellular matrix constituents. As a result, cart...

Traditional methods of cartilage tissue engineering rely on the use of scaffolds. Although successful chondrogenesis has been reported in scaffold-based constructs, the use of exogenous materials has limited their application due to eliciting host immunogenic responses, and potentially resulting in construct failure. As a result, tissue engineering...

Objective: When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are...

Objective: Cartilage tissue engineering is a promising approach to provide suitable materials for nasal reconstruction; however, it typically requires large numbers of cells. We have previously shown that a small number of chondrocytes cultivated within a continuous flow bioreactor can elicit substantial tissue growth, but translation to human cho...

Objective: The use of exogenous materials as scaffolds in cartilage tissue engineering has limited the clinical application of resultant constructs due to the risk of postoperative complications. In an effort to minimize such complications, we aim to generate human, scaffold-free auricular cartilaginous constructs. Study design: Laboratory study...

With over a million median sternotomy surgeries performed worldwide every year, sternal wound complications have posed a serious risk to the affected patients. A rigid therapeutic sternal fixation device has therefore become a necessity. In this work, the incorporation of up to 0.5 mol% of tantalum pentoxide (Ta2O5), in exchange for zinc oxide (ZnO...

This work considered the effect of both increasing additions of Strontium (Sr(2+)) and incubation time on solubility and both antibacterial and osteo-stimulatory effects of a series of glasses based on the B2O3-P2O5-CaCO3-Na2CO3-TiO2-SrCO3 series. The amorphous nature of all the glasses was confirmed by X-ray diffraction. Discs of each glass were i...

Surface wrinkled particles are ubiquitous in nature and present in different sizes and shapes, such as plant pollens and peppercorn seeds. These natural wrinkles provide the particles with advanced functions to survive and thrive in nature. In this work, by combining flow lithography and plasma treatment, we have developed a simple method that can...

Chondrocyte-seeded, photo-cross-linked hydrogels prepared from solutions containing 50% mass fractions of methacrylated glycol chitosan or methacrylated hyaluronic acid (MHA) with methacrylated chondroitin sulfate (MCS) are cultured in vitro under static conditions over 35 d to assess their suitability for load-bearing soft tissue repair. The photo...

Background: The use of chondrocytes for cartilage tissue engineering is hampered by the limited number of chondrocytes that can be harvested and potential dedifferentiation during cell expansion. While stem

Cellular mechanosensitivity is an important factor during the mechanical stimulation of tissue engineered cartilage. While the application of mechanical stimuli improves tissue growth and properties, chondrocytes also rapidly desensitize under prolonged loading thereby limiting its effectiveness. One potential method to mitigate load-induced desens...

Partial polymerization during photolitho-graphy is precisely controlled to obtain a partially cured (PCP) layer on the formed 3D microstructures. Upon plasma treatment, a 3D surface with morphologically tunable and spatially controllable wrinkles is obtained. The fabrication process is characterized and its ability to make various wrinkled microstr...

Mechanical stimulation is an effective method to increase extracellular matrix synthesis and to improve the mechanical properties of tissue-engineered cartilage constructs. In this chapter, we describe valuable methods of imposing direct mechanical stimuli (compression or shear) to tissue-engineered cartilage constructs as well as some common analy...

The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation and maturation within ‘biol...

Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechan...

In vitro tissue engineering enables the fabrication of functional tissues for tissue replacement. In addition, it allows us to build useful physiological and pathological models for mechanistic studies. However, the translation of in vitro tissue engineering into clinical therapies presents a number of technical and regulatory challenges. It is pos...

High modulus bi-continuous scaffolds were prepared by photo-crosslinking an aqueous suspension of chondrocytes and N-methacrylate glycol chitosan solution with a hydrolysable, hydrophobic, acrylated star-copolymer. Two acrylated star-copolymers were examined: poly(ε-caprolactone-co-D,L-lactide) (5446DLLACL) and poly(ε-caprolactone-co-trimethylene c...

Autologous osteochondral cartilage repair is a valuable reconstruction option for cartilage defects, but the accuracy to harvest and deliver osteochondral grafts remains problematic. We investigated whether image-guided methods (optically guided and template guided) can improve the outcome of these procedures. Fifteen sheep were operated to create...

Tissue engineering is a promising approach for articular cartilage repair. However, using current technologies, the developed engineered constructs generally do not possess an organized superficial layer, which contributes to the tissue's durability and unique mechanical properties. In this study, we investigated the efficacy of applying a moving p...

Confronted with articular cartilage's limited capacity for self-repair, joint resurfacing techniques offer an attractive treatment for damaged or diseased tissue. While tissue engineered cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of large defects. As rou...

The formation of cartilaginous tissue in vitro is a promising approach for the repair of damaged articular cartilage as a result of trauma or disease (e.g. osteoarthritis). It has been challenging, however, to engineer articular cartilage constructs suitable for joint resurfacing as the engineered tissues typically do not possess similar properties...

Stem cell interactions through paracrine cell signalling can regulate a range of cell responses, including metabolic activity, proliferation and differentiation. Moving towards the development of optimized tissue-engineering strategies with adipose-derived stem cells (ASCs), the focus of this study was on developing indirect co-culture models to st...

Articular cartilage suffers from a limited repair capacity when damaged by mechanical insult or degraded by disease, such as osteoarthritis. To remedy this deficiency, several medical interventions have been developed. One such method is to resurface the damaged area with tissue-engineered cartilage; however, the engineered tissue typically lacks t...

While mechanical stimuli can be used to enhance the properties of engineered cartilage, a promising alternative may be to directly harness the underlying mechanotransduction pathways responsible. Our initial studies on the adenosine triphosphate (ATP)-purinergic receptor pathway demonstrated that stimulation by exogenous ATP improved tissue growth...

The aim of this study was to fabricate a fibrous scaffold that closely resembled the micro-structural architecture and mechanical properties of collagen fibres found in the anterior cruciate ligament (ACL). To achieve this aim, fibrous scaffolds were made by electrospinning l-lactide based polymers. l-Lactide was chosen primarily due to its demonst...

The aim of this study was to determine the influence of a crimp-like microarchitecture within electrospun polymer scaffolds on fibroblast extracellular matrix (ECM) production when cultured under dynamic conditions. Electrospun poly(L-lactide-co-D,L-lactide) scaffolds possessing a wave pattern similar to collagen crimp (amplitude: 5 μm and waveleng...

Damaged articular cartilage in weight-bearing areas of the knee is not only painful for the patient, but also limits their Range of Motion (ROM). Because articular cartilage has limited self-healing potential, surgical treatment is necessary to restore the cartilage surface. The transplantation of multiple autologous osteochondral plugs (mosaicplas...

A photocurable two-phase scaffold with a bi-continuous morphology was designed and characterized for the repair of load bearing soft tissues. An N-methacrylate glycol chitosan (MGC) hydrogel phase was used to distribute the cells and enable cell growth once crosslinked. The second phase, an elastomerprepared from a star-poly(ε-caprolactone-co-D,L-l...

We describe and evaluate a computer algorithm that automatically develops a surgical plan for computer assisted mosaic arthroplasty, a technically demanding procedure in which a set of osteochondral plugs are transplanted from a non-load-bearing area of the joint to the site of a cartilage defect. We found that the algorithm produced plans that wer...

Adipose-derived stem cells (ASCs) represent an excellent cell source for the development of regenerative therapies for a broad variety of tissue disorders. Commonly, in vitro expansion is necessary to obtain sufficient cell populations for research purposes and clinical applications. Although it has been demonstrated that human ASCs can maintain th...

Success of mosaic arthroplasty requires that the transplanted plugs be positioned to reconstruct the curvature and height of the original articular surface. This case report demonstrates how to achieve correct plug positioning using patient-specific instrument guides manufactured on a 3D printer. Using a 3D computer model of bone and cartilage, the...

Tissue engineering is a promising approach for articular cartilage repair; however, it is challenging to produce adequate amounts of tissue in vitro from the limited number of cells that can be extracted from an individual. Relatively few cell expansion methods exist without the problems of de-differentiation and/or loss of potency. Recently, howev...

Harvesting osteochondral grafts results in a zone of chondrocyte death (ZCD) in and around the periphery of the graft, creating a barrier for chondrocytes to migrate to the graft periphery, thus limiting cartilage-to-cartilage healing. The purpose of this study was to repopulate the induced ZCD through the combined effects of collagenase treatment...

Semicrystalline poly(l-lactide-co-ε-caprolactone) (P(LLA-CL)) was used to produce electrospun fibers with diameters on the subcellular scale. P(LLA-CL) was chosen because it is biocompatible and its chemical and physical properties are easily tunable. The use of a rotating wire mandrel as a collection device in the electrospinning process, along wi...

Dehydration is known to cause an increase in the elastic modulus of bone tissue. However, it also causes structural changes (i.e. shrinkage) which can themselves significantly alter the mechanical properties, particularly in cancellous bone. The current study attempts to estimate the contribution of these two competing factors to the net change of...

Mechanical stimulation of engineered cartilage constructs is a commonly applied method used to accelerate tissue formation and improve the mechanical properties of the developed tissue. While the effects of compression and shear have been widely studied, the effect of tension has received relatively little attention. As articular cartilage in vivo...

In cancellous bone testing of cored samples, side artifacts are the underestimation of the true (i.e. in situ) mechanical properties due to the severing of the trabecular network during specimen preparation. Although other researchers have suggested correction factors derived from finite element method (FEM) models, it is proposed that side effects...

Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While this approach can be highly successful, it may be more efficient and effective to harness the known underlying mechanotransduction pathways responsible. With this aim, the purpose of this study was to assess the effect of dir...

End-constraint is needed when performing tensile and compressive testing of cancellous bone so that frictional and structural end-effects are minimized and the mechanical properties are not underestimated. Since many end-constrained testing techniques are limited to certain sites and species by the large specimen sizes required, reductions in overa...

This article proposes a novel electro-mechanical device to facilitate the investigation of mechanical stimuli on cells. The system was designed to dynamically apply a generalized, multi-axial state of deformation to a cell-encapsulated in a hydrogel cube by applying independent combinations of normal and shear forces to the faces of the cube. The c...

This article proposes a novel electro-mechanical device to facilitate the investigation of mechanical stimuli on cells. The system was designed to dynamically apply a generalized, multi-axial state of deformation to a cell-encapsulated in a hydrogel cube by applying independent combinations of normal and shear forces to the faces of the cube. The c...

Degeneration of the intervertebral disc (IVD) involves structural changes in the annulus fibrosus (AF), which could alter the mechanical forces imposed on the nucleus pulposus (NP) tissue. This could contribute to degenerative changes that occur in the NP. The purpose of the study was to determine whether circumferential constraint affects anabolic...

Defects in articular cartilage can be repaired through osteochondral transplantation (mosaic arthroplasty), where osteochondral plugs from non-weight-bearing areas of the joint are transferred to the defect site. Incongruity between the plug surface and the adjacent cartilage results in increased contact pressures and poorer outcomes. We compare th...

Kidney stone patients often have a decrease in BMD. It is unclear if reduced BMD is caused by a primary disorder of bone or dietary factors. To study the independent effects of hypercalciuria on bone, we used genetic hypercalciuric stone-forming (GHS) rats. GHS and control (Ctl) rats were fed a low Ca (0.02% Ca, LCD) or a high Ca (1.2% Ca, HCD) die...

Our objective was to examine the potential of a genipin cross-linked human fibrin hydrogel system as a scaffold for articular cartilage tissue engineering. Human articular chondrocytes were incorporated into modified human fibrin gels and evaluated for mechanical properties, cell viability, gene expression, extracellular matrix production and subcu...

The use of bioreactors for cartilage tissue engineering has become increasingly important as traditional batch-fed culture is not optimal for in vitro tissue growth. Most tissue engineering bioreactors rely on convection as the primary means to provide mass transfer; however, convective transport can also impart potentially unwanted and/or uncontro...

Herein we report on the development and characterization of a biodegradable composite scaffold for ligament tissue engineering based on the fundamental morphological features of the native ligament. An aligned fibrous component was used to mimic the fibrous collagen network and a hydrogel component to mimic the proteoglycan-water matrix of the liga...

Tissue-engineered constructs grown in vitro tend to have random arrangements of cells and extracellular matrix (ECM) and much research effort is aimed at developing long-range organization in tissue-engineered constructs. Contact guidance, which utilizes substrates with topographical patterns of the scale of single cells (0.1-100 microm) to limit c...

Tissue engineering is a promising approach for articular cartilage repair; however, it still has proven a challenge to produce tissue from the limited number of cells that can be extracted from a single individual. Relatively few cell expansion methods exist without the problems of dedifferentiation and/or loss of potency. Previously, it has been s...

Recent focus in cartilage tissue engineering has been to develop functional tissue that can survive after implantation. One such determinant is the ability of the engineered tissue to be able to sustain its metabolic activity post-implantation. In vivo, chondrocytes contain stores of intracellular glycogen to support metabolism and it is unknown wh...

Tissue engineering is a promising approach for articular cartilage repair; however, it still has proven a challenge to produce substantial quantities of tissue from the limited number of cells that can be extracted from a single individual. Although several approaches have been investigated to enhance the production of cartilaginous tissue in vitro...