Abstract:
:Successful osteochondral defect repair requires regenerating the subchondral bone whilst simultaneously promoting the development of an overlying layer of articular cartilage that is resistant to vascularization and endochondral ossification. During skeletal development articular cartilage also functions as a surface growth plate, which postnatally is replaced by a more spatially complex bone-cartilage interface. Motivated by this developmental process, the hypothesis of this study is that bi-phasic, fibre-reinforced cartilaginous templates can regenerate both the articular cartilage and subchondral bone within osteochondral defects created in caprine joints. To engineer mechanically competent implants, we first compared a range of 3D printed fibre networks (PCL, PLA and PLGA) for their capacity to mechanically reinforce alginate hydrogels whilst simultaneously supporting mesenchymal stem cell (MSC) chondrogenesis in vitro. These mechanically reinforced, MSC-laden alginate hydrogels were then used to engineer the endochondral bone forming phase of bi-phasic osteochondral constructs, with the overlying chondral phase consisting of cartilage tissue engineered using a co-culture of infrapatellar fat pad derived stem/stromal cells (FPSCs) and chondrocytes. Following chondrogenic priming and subcutaneous implantation in nude mice, these bi-phasic cartilaginous constructs were found to support the development of vascularised endochondral bone overlaid by phenotypically stable cartilage. These fibre-reinforced, bi-phasic cartilaginous templates were then evaluated in clinically relevant, large animal (caprine) model of osteochondral defect repair. Although the quality of repair was variable from animal-to-animal, in general more hyaline-like cartilage repair was observed after 6 months in animals treated with bi-phasic constructs compared to animals treated with commercial control scaffolds. This variability in the quality of repair points to the need for further improvements in the design of 3D bioprinted implants for joint regeneration. STATEMENT OF SIGNIFICANCE: Successful osteochondral defect repair requires regenerating the subchondral bone whilst simultaneously promoting the development of an overlying layer of articular cartilage. In this study, we hypothesised that bi-phasic, fibre-reinforced cartilaginous templates could be leveraged to regenerate both the articular cartilage and subchondral bone within osteochondral defects. To this end we used 3D printed fibre networks to mechanically reinforce engineered transient cartilage, which also contained an overlying layer of phenotypically stable cartilage engineered using a co-culture of chondrocytes and stem cells. When chondrogenically primed and implanted into caprine osteochondral defects, these fibre-reinforced bi-phasic cartilaginous grafts were shown to spatially direct tissue development during joint repair. Such developmentally inspired tissue engineering strategies, enabled by advances in biofabrication and 3D printing, could form the basis of new classes of regenerative implants in orthopaedic medicine.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Critchley S,Sheehy EJ,Cunniffe G,Diaz-Payno P,Carroll SF,Jeon O,Alsberg E,Brama PAJ,Kelly DJdoi
10.1016/j.actbio.2020.05.040subject
Has Abstractpub_date
2020-09-01 00:00:00pages
130-143eissn
1742-7061issn
1878-7568pii
S1742-7061(20)30319-6journal_volume
113pub_type
杂志文章abstract::The poor delivery of nanoparticles to target cancer cells hinders their success in the clinical setting. In this work, an alternative target readily available for circulating nanoparticles has been selected to eliminate the need for nanoparticle penetration in the tissue: the tumor blood vessels. A tumor endothelium-t...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.11.004
更新日期:2020-01-01 00:00:00
abstract::In total hip arthroplasty, osteolysis of the acetabulum often occurs at the backside of cups in the area of screw holes, indicating a clinically relevant amount of polyethylene (PE) wear particles in this area. In order to avoid a possible migration of wear particles to the acetabulum-bone, screw hole plugs are provid...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.07.050
更新日期:2019-10-01 00:00:00
abstract:UNLABELLED:Small interfering RNAs (siRNAs) are extensively studied due to their promising potential as therapeutic agents for a wide variety of diseases, including cancer. However, efficient delivery of siRNAs to target cells and tissues is problematic due to a lack of suitable delivery vehicles. In this work, we devel...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.07.026
更新日期:2015-10-01 00:00:00
abstract::The uptake and trafficking of NPs is impacted by several attributes such as size, shape, surface charge and importantly by surface ligands that can interact with the cell plasma membrane. We envision that NPs which can be readily modified in aqueous environments will be key to engineering patient-specific nanotherapeu...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.08.038
更新日期:2020-10-15 00:00:00
abstract::Osteoarthritis (OA), is a common musculoskeletal disorder that will progressively increase in older populations and is expected to be the most dominant cause of disability in the world population by 2030. The progression of OA is controlled by a multi-factorial pathway that has not been completely elucidated and under...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2021.01.003
更新日期:2021-01-12 00:00:00
abstract::In order to expand the properties and applications of aliphatic absorbable polyesters, a new biodegradable block copolymer family, poly(ester amide)-b-poly(ε-caprolactone) (PEA-b-PCL), was synthesized and characterized. These copolymers were synthesized by first preparing l-phenylalanine-based poly(ester amide) macroi...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.07.027
更新日期:2012-12-01 00:00:00
abstract::Differentiation of stem and progenitor cells routinely relies on the application of soluble growth factors, an approach that enables temporal control of cell fate but enables no spatial control of the differentiation process. Angiogenic progenitor cells derived from mouse embryonic stem cells (ESCs) were differentiate...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.12.005
更新日期:2010-06-01 00:00:00
abstract::Recapitulation of endochondral ossification leads to a new concept of bone tissue engineering via a cartilage intermediate as an osteoinductive template. In this study, we aimed to investigate the influence of in vitro chondrogenic priming time for the creation of cartilage template on the in vivo endochondral bone fo...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.11.029
更新日期:2015-02-01 00:00:00
abstract::The development of vascular grafts has focused on finding a biomaterial that is non-thrombogenic, minimizes intimal hyperplasia, matches the mechanical properties of native vessels and allows for regeneration of arterial tissue. In this study, the structural and mechanical properties and the vascular cell compatibilit...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.08.001
更新日期:2012-01-01 00:00:00
abstract::Recently, a significant amount of effort has been dedicated to understanding factors that influence the functionality of bio-electronic sensors and to development of novel coating technologies for modifying biosensor surfaces. Due to its well-known biocompatibility, alginate hydrogel (HG) has been used as a coating ma...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.07.034
更新日期:2010-01-01 00:00:00
abstract::In this research, the flexural performance of hedgehog spines is investigated in four ways. First, X-ray micro-computed tomography (μCT) is employed to analyze the complex internal architecture of hedgehog spines. μCT images reveal distinct structural morphology, characterized by longitudinal stringers and transverse ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.04.036
更新日期:2019-08-01 00:00:00
abstract::Cellular transplantation is now closer to becoming a practical clinical strategy to repair, regenerate or restore the function of skin, muscle, nerves and pancreatic islets. In this study we sought to develop a simple injectable collagen matrix that would preserve the normal cellular organization of skin cells. Three ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.04.024
更新日期:2011-08-01 00:00:00
abstract::Molecular imprinting is a new and rapidly evolving technique used to create synthetic receptors and it possesses great potential in a number of applications in the life sciences. Keeping in mind the therapeutic importance of 5-fluorouracil (5-FU) and the technological significance of molecular imprinting polymers, the...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.03.017
更新日期:2008-09-01 00:00:00
abstract::Human pluripotent stem cell derived neural progenitor cells (hNPCs) have the unique properties of long-term in vitro expansion as well as differentiation into the various neurons and supporting cell types of the central nervous system (CNS). Because of these characteristics, hNPCs have tremendous potential in the mode...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.05.008
更新日期:2018-07-01 00:00:00
abstract:UNLABELLED:Although attenuated malaria parasitized red blood cells (pRBCs) are promising vaccine candidates, their application in humans may be restricted for ethical and regulatory reasons. Therefore, we developed an organic microparticle-based delivery platform as a whole parasite malaria-antigen carrier to mimic pRB...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.08.020
更新日期:2016-10-15 00:00:00
abstract::Perinatal tissues are an abundant source of human extracellular matrix proteins, growth factors and stem cells with proved potential use in a wide range of therapeutic applications. Due to their placental origin, these tissues possess unique biological properties, including being angiogenic, anti-inflammatory, anti-fi...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2020.04.035
更新日期:2020-07-01 00:00:00
abstract:UNLABELLED:Natural amino acids are zwitterionic molecules and the good biocompatibility promises them potential candidates as anti-fouling materials. Here, we developed a new method to functionalize silica nanoparticles with a natural amino acid-based anti-fouling layer. Amino acids were covalently immobilized on 3-ami...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.03.035
更新日期:2016-08-01 00:00:00
abstract::Three dimensional (3D) printing is highly amenable to the fabrication of tissue-engineered organs of a repetitive microstructure such as the liver. The creation of uniform and geometrically repetitive tissue scaffolds can also allow for the control over cellular aggregation and nutrient diffusion. However, the effect ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.12.042
更新日期:2018-03-15 00:00:00
abstract::Combination therapy offers promising opportunities for treating advanced non-small cell lung cancer (NSCLC). Here, we established a chitosan-based nanocomplex CE7Q/CQ/S to deliver molecular-targeted drug erlotinib (Er), Survivin shRNA-expressing plasmid (SV), and photothermal agent heptamethine cyanine dye (Cy7) in on...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.03.004
更新日期:2020-04-15 00:00:00
abstract::The combinatorial polymer library approach has been proven to be effective for the optimization of therapeutic delivery systems. The library of polymers with chemical diversity has been synthesized by (i) polymerization of functionalized monomers or (ii) post-polymerization modification of reactive polymers. Most scie...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2018.04.010
更新日期:2018-06-01 00:00:00
abstract::Hydrogels that solidify in response to a dual, physical and chemical, mechanism upon temperature increase were fabricated and characterized. The hydrogels were based on N-isopropylacrylamide, which renders them thermoresponsive, and contained covalently cross-linkable moieties in the macromers. The effects of the macr...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.12.027
更新日期:2011-04-01 00:00:00
abstract::This paper reports a new method of cross-linking electrospun zein fibers using citric acid as a non-toxic cross-linker to enhance the water stability and cytocompatibility of zein fibers for tissue engineering and other medical applications. The electrospun structure has many advantages over other types of structures ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.04.024
更新日期:2010-10-01 00:00:00
abstract::While several biological processes have been shown to be useful for the production of well-designed, inorganic nanostructures, the mechanism(s) controlling the size and shape of nano and micron size particles remains elusive. Here we report on the controlled size- and shape-specific production of gold nanostructures u...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.01.019
更新日期:2010-07-01 00:00:00
abstract::The combination of hydrogels and calcium phosphate particles is emerging as a well-established trend for bone substitutes. Besides acting as binders for the inorganic phase, hydrogels within these hybrid materials can modulate cell colonization physically and biologically. The influence of hydrogels on the healing pro...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2012.11.022
更新日期:2013-03-01 00:00:00
abstract::This paper presents a strain-mediated phenomenological corrosion model, based on the discrete finite element modelling method which was developed for use with the ANSYS Implicit finite element code. The corrosion model was calibrated from experimental data and used to simulate the corrosion performance of a WE43 magne...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.04.020
更新日期:2017-06-01 00:00:00
abstract::Cell-instructive hydrogels are attractive for skin repair and regeneration, serving as interactive matrices to promote cell adhesion, cell-driven remodeling and de novo deposition of extracellular matrix components. This paper describes the synthesis and photocrosslinking of cell-instructive pectin hydrogels using cel...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.11.016
更新日期:2018-01-15 00:00:00
abstract::Vitamin D3 modulates immune response, induces endogenous antimicrobial peptide production, and enhances innate immunity to defend against infections. These findings suggest that incorporating vitamin D3 into medical devices or scaffolds could positively modulate host immune response and prevent infections. In the curr...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.08.005
更新日期:2019-10-01 00:00:00
abstract::During the past two decades, research on ceramic scaffolds for bone regeneration has progressed rapidly; however, currently available porous scaffolds remain unsuitable for load-bearing applications. The key to success is to apply microstructural design strategies to develop ceramic scaffolds with mechanical propertie...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.02.039
更新日期:2013-06-01 00:00:00
abstract::Engineered tissues are highly limited by poor vascularization in vivo, leading to hypoxia. In order to overcome this challenge, we propose the use of photosynthetic biomaterials to provide oxygen. Since photosynthesis is the original source of oxygen for living organisms, we suggest that this could be a novel approach...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.12.012
更新日期:2015-03-01 00:00:00
abstract:UNLABELLED:The generation of tissue-engineered blood vessel substitutes remains an ongoing challenge for cardiovascular tissue engineering. Full biocompatibility and immediate availability have emerged as central issues for clinical use. To address these issues, we developed a technique that allows the generation of hi...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.10.012
更新日期:2016-01-01 00:00:00