Cartilage and Bone Regeneration—How Close Are We to Bedside? (original) (raw)
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Biofunctional Materials for Bone and Cartilage Tissue Engineering
Encyclopedia of Smart Materials, 2022
Regenerative medicine is a promising new area of research that offers potential to treat diseased and injured tissue. In particular, the development of new biomaterials-based approaches show promise for the treatment of challenging bone and cartilage injuries. Recent trends have focused on the development of biofunctional materials that have bioactive properties and are capable of supporting and promoting new tissue formation during the tissue repair process. This article discusses current biomaterial-based approaches for bone and 2 cartilage repair and highlights emerging material functionalization methodologies including surface modification, growth factor delivery, cell-seeding strategies and gene therapy.
Osteochondral defect repair poses a significant challenge in its reconstruction as the damage is presented in both articular cartilage and the underlying subchondral bone. Tissue engineering approaches have utilized various scaffolds in combination of stem cells and growth factors to regenerate the defect. Still significant challenge remains in creating a scaffold structure that supports the proliferation and differentiation of bone marrow stromal cells (BMSCs) into chondrocytes and osteoblasts while providing the appropriate mechanical stability. Present manuscript reports the fabrication and characterization of a biphasic scaffold system derived from biodegradable polymers such as poly(lactic acid-glycolic acid) (PLGA) as a hard shell and polycaprolactone (PCL) a soft component. Collectively this biphasic scaffold was able to withstand physiological load up to 10,000 cycles in a cyclic compressive testing. The scaffold surface was decorated with PCL aligned nanofibers contacting chondroitin sulfate and hyaluronic acid and nanofibers were cross-linked via carbodiimide linkages to retain these bioactive molecules over the culture period. The present study aims to show the potential of these bioactive scaffolds for the repair ofosteochondral defects. Scaffolds were characterized by Fourier transform infra-red spectroscopy, optical microscopy and cyclic compressive testing. Primary rat bone marrow stem cells were seeded onto scaffolds and cell proliferation and differentiation was evaluated using RTPCR and immunohistochemistry. RT-PCR indicated that the scaffold was able to stimulate the different regions of osteochondral tissue: collagen type II and aggrecan expression in the cartilage region and BMP-2 in the bone region. Similarly protein secretion with induced alignment was confirmed with immunofluorescence imaging. This novel hybrid scaffold shows promising results in the regeneration of cartilage tissue as well as the underlying subchondral bone.
Tissue engineering and cell therapy of cartilage and bone
Matrix Biology, 2003
Trauma and disease of bones and joints, frequently involving structural damage to both the articular cartilage surface and the subchondral bone, result in severe pain and disability for millions of people worldwide and represent major challenges for the orthopedic surgeons. Therapeutic repair of skeletal tissues by tissue engineering has raised the interest of the scientific community, providing very promising results in preclinical animal models and clinical pilot studies. In this review, we discuss this approach. The choice of a proper cell type is addressed. The use of terminally differentiated cells, as in the case of autologous chondrocyte implantation, is compared with the advantagesydisadvantages of using more undifferentiated cell types, such as stem cells or early mesenchymal progenitors that retain multi-lineage and self-renewal potentials. The need for proper scaffold matrices is also examined, and we provide a brief overview of their fundamental properties. A description of the natural and biosynthetic materials currently used for reconstruction purposes, either of cartilage or bone, is given. Finally, we highlight the positive aspects and the remaining problems that will drive future research in articular cartilage and bone repair. ᮊ
Revista de Chimie
The ability of damaged articular cartilage to recover with normal hyaline cartilage is limited. Our aim was to study the mechanism of in vivo cartilage repair in case of severe osteochondral lesions using a three-dimensional matrix implanted without any preseeded cells in the osteochondral defect in a rabbit model. According to the ICRS scores from macroscopic observations of the femoral condyles, the average scores in the scaffold groups were higher than those in the control groups at every time (P[0.001). Histological examination of the ostheochondral defects, revealed regeneration of new tissue with hyaline-like cartilage features only in matrix groups. At twelve weeks from implantation, complete filling of the defect with hyaline cartilage with a tendency of mineralization and the absence of implant material is observed. The superficial area of the defect is completely covered with hyaline-like cartilage. The scaffold used leaded to the regeneration of articular tissue with an o...
Scaffolding Biomaterials for Cartilage Regeneration
Journal of Nanomaterials, 2014
Completely repairing of damaged cartilage is a difficult procedure. In recent years, the use of tissue engineering approach in which scaffolds play a vital role to regenerate cartilage has become a new research field. Investigating the advances in biological cartilage scaffolds has been regarded as the main research direction and has great significance for the construction of artificial cartilage. Native biological materials and synthetic polymeric materials have their advantages and disadvantages. The disadvantages can be overcome through either physical modification or biochemical modification. Additionally, developing composite materials, biomimetic materials, and nanomaterials can make scaffolds acquire better biocompatibility and mechanical adaptability.
Current Concepts and Challenges in Osteochondral Tissue Engineering and Regenerative Medicine
ACS Biomaterials Science & Engineering, 2015
In the last few years, great progress has been made to validate tissue engineering strategies in preclinical studies and clinical trials on the regeneration of osteochondral defects. In the preclinical studies, one of the dominant strategies comprises the development of biomimetic/bioactive scaffolds, which are used alone or incorporated with growth factors and/or stem cells. Many new trends are emerging for modulation of stem cell fate towards osteogenic and chondrogenic differentiations, but bone/cartilage interface regeneration and physical stimulus have been showing great promise. Besides the matrix-associated autologous chondrocyte implantation (MACI) procedure, the matrix-associated stem cells implantation (MASI) and layered scaffolds in acellular or cellular strategy are also applied in clinic. This review outlines the progresses at preclinical and clinical levels, and identifies the new challenges in osteochondral tissue engineering. Future perspectives are provided, e.g., the applications of extracellular matrix-like biomaterials, computer-aided design/manufacture of osteochondral implant and reprogrammed cells for osteochondral regeneration.
Advances in Porous Scaffold Design for Bone and Cartilage Tissue Engineering and Regeneration
Tissue Engineering Part B-reviews, 2019
Tissue engineering of bone and cartilage has progressed from simple to sophisticated materials with defined porosity, surface features, and the ability to deliver biological factors. To avoid eliciting a foreign body response due to inclusion of allogeneic cells, advances in functional scaffold design harness the endogenous ability of the body to regenerate. We review advancements in the surface and structural properties of typical polymeric, ceramic, and metallic scaffolds for orthopedic use. First, we provide an overview of methods and materials, with a focus on additive manufacturing and electrospinning. Multidimensional physical properties of scaffolds, including three-dimensional macrostructure, pore design, and two-dimensional hierarchical surface roughness, allow tissue regeneration at different spatial and temporal scales. Enhanced biological response can be achieved through surface functionalization and the use of exogenous factors. Finally, different in vitro and in vivo models are discussed for translation of these technologies for clinical use.
Development of Biomimetic and Bioactive 3D Nanocomposite Scaffolds for Osteochondral Regeneration
Volume 3B: Biomedical and Biotechnology Engineering, 2013
Osteochondral tissue is composed of ordered and random biological nanostructures and can, in principal, be classified as a nanocomposite material. Thus, the objective of this research is to develop a novel biomimetic biphasic nanocomposite scaffold via a series of 3D fabricating techniques for osteochondral tissue regeneration. For this purpose, a highly porous Poly(caprolactone) (PCL) bone layer with bone morphogenetic protein-2 (BMP-2)-encapsulated Poly(dioxanone) (PDO) nanospheres and nanocrystalline hydroxyapatite was photocrosslinked to a Poly(ethylene glycol)-diacrylate (PEG-DA) cartilage layer containing transforming growth factor-β1 (TGF-β1)-encapsulated PLGA nanospheres. Novel tissue-specific growth factor-encapsulated nanospheres were efficiently fabricated via a wet co-axial electrospraying technique. Integration and porosity of the distinct layers was achieved via co-porogen leaching and ultraviolet (UV) photocrosslinking of water soluble poly(ethylene glycol) (PEG) and ...
Journal of Biological Engineering
Tissue engineering, as an interdisciplinary approach, is seeking to create tissues with optimal performance for clinical applications. Various factors, including cells, biomaterials, cell or tissue culture conditions and signaling molecules such as growth factors, play a vital role in the engineering of tissues. In vivo microenvironment of cells imposes complex and specific stimuli on the cells, and has a direct effect on cellular behavior, including proliferation, differentiation and extracellular matrix (ECM) assembly. Therefore, to create appropriate tissues, the conditions of the natural environment around the cells should be well imitated. Therefore, researchers are trying to develop biomimetic scaffolds that can produce appropriate cellular responses. To achieve this, we need to know enough about biomimetic materials. Scaffolds made of biomaterials in musculoskeletal tissue engineering should also be multifunctional in order to be able to function better in mechanical properti...
Developing repair strategies for osteochondral tissue presents complex challenges due to its interfacial nature and complex zonal structure, consisting of subchondral bone, intermediate calcified cartilage and the superficial cartilage regions. In this study, the long term ability of a multi-layered biomimetic collagen-based scaffold to repair osteochondral defects is investigated in a large animal model: namely critical sized lateral trochlear ridge (TR) and medial femoral condyle (MC) defects in the caprine stifle joint. The study thus presents the first data in a clinically applicable large animal model. Scaffold fixation and early integration was demonstrated at 2 weeks post implantation. Macroscopic analysis demonstrated improved healing in the multi-layered scaffold group compared to empty defects and a market approved synthetic polymer osteochondral scaffold groups at 6 and 12 months post implantation. Radiological analysis demonstrated superior subchondral bone formation in both defect sites in the multi-layered scaffold group as early as 3 months, with complete regeneration of subchondral bone by 12 months. Histological analysis confirmed the formation of well-structured subchondral trabecular bone and hyaline-like cartilage tissue in the multi-layered scaffold group by 12 months with restoration of the anatomical tidemark. Demonstration of improved healing following treatment with this natural polymer scaffold, through the recruitment of host cells with no requirement for pre-culture, shows the potential of this device for the treatment of patients presenting with osteochondal lesions.