scholarly journals Biological perspectives and current biofabrication strategies in osteochondral tissue engineering

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Cian Vyas ◽  
Hussein Mishbak ◽  
Glen Cooper ◽  
Chris Peach ◽  
Ruben F. Pereira ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Rational Design ◽  
Therapeutic Interventions ◽  
Ageing Population ◽  
Clinical Practices ◽  
Tissue Constructs ◽  
Systems Research ◽  
Starting Point ◽  
Osteochondral Tissue

Abstract Articular cartilage and the underlying subchondral bone are crucial in human movement and when damaged through disease or trauma impacts severely on quality of life. Cartilage has a limited regenerative capacity due to its avascular composition and current therapeutic interventions have limited efficacy. With a rapidly ageing population globally, the numbers of patients requiring therapy for osteochondral disorders is rising, leading to increasing pressures on healthcare systems. Research into novel therapies using tissue engineering has become a priority. However, rational design of biomimetic and clinically effective tissue constructs requires basic understanding of osteochondral biological composition, structure, and mechanical properties. Furthermore, consideration of material design, scaffold architecture, and biofabrication strategies, is needed to assist in the development of tissue engineering therapies enabling successful translation into the clinical arena. This review provides a starting point for any researcher investigating tissue engineering for osteochondral applications. An overview of biological properties of osteochondral tissue, current clinical practices, the role of tissue engineering and biofabrication, and key challenges associated with new treatments is provided. Developing precisely engineered tissue constructs with mechanical and phenotypic stability is the goal. Future work should focus on multi-stimulatory environments, long-term studies to determine phenotypic alterations and tissue formation, and the development of novel bioreactor systems that can more accurately resemble the in vivo environment.

Novel HA-PVA/NOCC bilayered scaffold for osteochondral tissue-engineering applications – Fabrication, characterization, in vitro and in vivo biocompatibility study

2013 ◽  
Vol 113 ◽  
pp. 25-29 ◽  
Author(s):  
Nurul Syuhada Ibrahim ◽  
Genasan Krishnamurithy ◽  
Hanumantha Rao Balaji Raghavendran ◽  
Subramaniam Puvaneswary ◽  
Ng Wuey Min ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Engineering Applications ◽  
Osteochondral Tissue ◽  
Osteochondral Tissue Engineering ◽  
Biocompatibility Study

scholarly journals Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr/Zn Folates for Osteochondral Tissue Engineering

Polymers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 12
Author(s):  
Gerardo Asensio ◽  
Lorena Benito-Garzón ◽  
Rosa Ana Ramírez-Jiménez ◽  
Yasmina Guadilla ◽  
Julian Gonzalez-Rubio ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Hyaluronic Acid ◽  
Folic Acid ◽  
In Vitro Release ◽  
Biologically Active ◽  
Human Articular Cartilage ◽  
Promising Alternative ◽  
Osteochondral Tissue

Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr2+, Zn2+ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.

scholarly journals In vivo tissue engineering of a trilayered leaflet-shaped tissue construct

2020 ◽  
Vol 15 (1) ◽  
pp. 1177-1192
Author(s):  
Soumen Jana ◽  
Amir Lerman
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Heart Valve ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Tissue Constructs ◽  
In Vivo Tissue Engineering ◽  
Engineered Tissue ◽  
Tissue Construct

Aim: We aimed to develop a leaflet-shaped trilayered tissue construct mimicking the morphology of native heart valve leaflets. Materials & methods: Electrospinning and in vivo tissue engineering methods were employed. Results: We developed leaflet-shaped microfibrous scaffolds, each with circumferentially, randomly and radially oriented three layers mimicking the trilayered, oriented structure of native leaflets. After 3 months in vivo tissue engineering with the scaffolds, the generated leaflet-shaped tissue constructs had a trilayered structure mimicking the orientations of native heart valve leaflets. Presence of collagen, glycosaminoglycans and elastin seen in native leaflets was observed in the engineered tissue constructs. Conclusion: Trilayered, oriented fibrous scaffolds brought the orientations of the infiltrated cells and their produced extracellular matrix proteins into the constructs.

scholarly journals Continuous Passive Motion Promotes and Maintains Chondrogenesis in Autologous Endothelial Progenitor Cell-Loaded Porous PLGA Scaffolds during Osteochondral Defect Repair in a Rabbit Model

2019 ◽  
Vol 20 (2) ◽  
pp. 259 ◽  
Author(s):  
Hsueh-Chun Wang ◽  
Tzu-Hsiang Lin ◽  
Nai-Jen Chang ◽  
Horng-Chaung Hsu ◽  
Ming-Long Yeh
Keyword(s):  
Tissue Engineering ◽  
Weight Bearing ◽  
Continuous Passive Motion ◽  
Clinical Practices ◽  
Plga Scaffold ◽  
Endothelial Progenitor ◽  
Passive Motion ◽  
Extracellular Matrix Components ◽  
Osteochondral Tissue ◽  
Osteochondral Tissue Engineering

Continuous passive motion (CPM) is widely used after total knee replacement. In this study, we investigated the effect of CPM combined with cell-based construct-transplantation in osteochondral tissue engineering. We created osteochondral defects (3 mm in diameter and 3 mm in depth) in the medial femoral condyle of 36 knees and randomized them into three groups: ED (empty defect), EPC/PLGA (endothelial progenitor cells (EPCs) seeded in the poly lactic-co-glycolic acid (PLGA) scaffold), or EPC/PLGA/CPM (EPC/PLGA scaffold complemented with CPM starting one day after transplantation). We investigated the effects of CPM and the EPC/PLGA constructs on tissue restoration in weight-bearing sites by histological observation and micro-computed tomography (micro-CT) evaluation 4 and 12 weeks after implantation. After CPM, the EPC/PLGA construct exhibited early osteochondral regeneration and prevention of subchondral bone overgrowth and cartilage degeneration. CPM did not alter the microenvironment created by the construct; it up-regulated the expression of the extracellular matrix components (glycosaminoglycan and collagen), down-regulated bone formation, and induced the biosynthesis of lubricin, which appeared in the EPC/PLGA/CPM group after 12 weeks. CPM can provide promoting signals during osteochondral tissue engineering and achieve a synergistic effect when combined with EPC/PLGA transplantation, so it should be considered a non-invasive treatment to be adopted in clinical practices.

Rational design and protein engineering of growth factors for regenerative medicine and tissue engineering

2009 ◽  
Vol 37 (4) ◽  
pp. 717-721 ◽  
Author(s):  
Andrew J. Moss ◽  
Shikha Sharma ◽  
Nicholas P.J. Brindle
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Protein Engineering ◽  
Rational Design ◽  
Receptor Activation ◽  
Natural Growth ◽  
Combinatorial Protein Engineering ◽  
Sites Of Action ◽  
Synthetic Growth

Growth factors provide key instructive cues for tissue formation and repair. However, many natural growth factors are limited in their usefulness for tissue engineering and regenerative applications by their poor retention at desired sites of action, short half-lives in vivo, pleiotropic actions and other features. In the present article, we review approaches to rational design of synthetic growth factors based on mechanisms of receptor activation. Such synthetic molecules can function as simplified ligands with potentially tunable specificity and action. Rational and combinatorial protein engineering techniques allow introduction of additional features into these synthetic growth molecules, as well as natural growth factors, which significantly enhance their therapeutic utility.

scholarly journals Rational design of a mutation to investigate the role of the brain protein TRIP8b in limiting the cAMP response of HCN channels in neurons

2020 ◽  
Vol 152 (9) ◽  
Author(s):  
Alessandro Porro ◽  
Anna Binda ◽  
Matteo Pisoni ◽  
Chiara Donadoni ◽  
Ilaria Rivolta ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Rational Design ◽  
Regulatory Subunit ◽  
Hcn Channels ◽  
Subcellular Targeting ◽  
Mutant Channel ◽  
Channel Trafficking ◽  
Starting Point

TRIP8b (tetratricopeptide repeat–containing Rab8b-interacting protein) is the neuronal regulatory subunit of HCN channels, a family of voltage-dependent cation channels also modulated by direct cAMP binding. TRIP8b interacts with the C-terminal region of HCN channels and controls both channel trafficking and gating. The association of HCN channels with TRIP8b is required for the correct expression and subcellular targeting of the channel protein in vivo. TRIP8b controls HCN gating by interacting with the cyclic nucleotide-binding domain (CNBD) and competing for cAMP binding. Detailed structural knowledge of the complex between TRIP8b and CNBD was used as a starting point to engineer a mutant channel, whose gating is controlled by cAMP, but not by TRIP8b, while leaving TRIP8b-dependent regulation of channel trafficking unaltered. We found two-point mutations (N/A and C/D) in the loop connecting the CNBD to the C-linker (N-bundle loop) that, when combined, strongly reduce the binding of TRIP8b to CNBD, leaving cAMP affinity unaltered both in isolated CNBD and in the full-length protein. Proof-of-principle experiments performed in cultured cortical neurons confirm that the mutant channel provides a genetic tool for dissecting the two effects of TRIP8b (gating versus trafficking). This will allow the study of the functional role of the TRIP8b antagonism of cAMP binding, a thus far poorly investigated aspect of HCN physiology in neurons.

scholarly journals Microvascular fragment spheroids: Three-dimensional vascularization units for tissue engineering and regeneration

2021 ◽  
Vol 12 ◽  
pp. 204173142110355
Author(s):  
Lisa Nalbach ◽  
Danièle Müller ◽  
Selina Wrublewsky ◽  
Wolfgang Metzger ◽  
Michael D Menger ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Function ◽  
Smooth Muscle Actin ◽  
Three Dimensional ◽  
Stromal Vascular Fraction ◽  
Muscle Actin ◽  
Tissue Constructs ◽  
First Time ◽  
Tissue Defects

Adipose tissue-derived microvascular fragments (MVF) serve as vascularization units in tissue engineering and regenerative medicine. Because a three-dimensional cellular arrangement has been shown to improve cell function, we herein generated for the first time MVF spheroids to investigate whether this further increases their vascularization potential. These spheroids exhibited a morphology, size, and viability comparable to that of previously introduced stromal vascular fraction (SVF) spheroids. However, MVF spheroids contained a significantly higher number of CD31-positive endothelial cells and α-smooth muscle actin (SMA)-positive perivascular cells, resulting in an enhanced angiogenic sprouting activity. Accordingly, they also exhibited an improved in vivo vascularization and engraftment after transplantation into mouse dorsal skinfold chambers. These findings indicate that MVF spheroids are superior to SVF spheroids and, thus, may be highly suitable to improve the vascularization of tissue defects and implanted tissue constructs.

Mechanobiology in Tendon, Ligament, and Skeletal Muscle Tissue Engineering

2021 ◽  
Vol 143 (7) ◽  
Author(s):  
Michael T. K. Bramson ◽  
Sarah K. Van Houten ◽  
David T. Corr
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Mechanical Loading ◽  
Mechanical Stimulation ◽  
Self Assembly ◽  
Tissue Constructs ◽  
Active Contraction ◽  
Matrix Production

Abstract Tendon, ligament, and skeletal muscle are highly organized tissues that largely rely on a hierarchical collagenous matrix to withstand high tensile loads experienced in activities of daily life. This critical biomechanical role predisposes these tissues to injury, and current treatments fail to recapitulate the biomechanical function of native tissue. This has prompted researchers to pursue engineering functional tissue replacements, or dysfunction/disease/development models, by emulating in vivo stimuli within in vitro tissue engineering platforms—specifically mechanical stimulation, as well as active contraction in skeletal muscle. Mechanical loading is critical for matrix production and organization in the development, maturation, and maintenance of native tendon, ligament, and skeletal muscle, as well as their interfaces. Tissue engineers seek to harness these mechanobiological benefits using bioreactors to apply both static and dynamic mechanical stimulation to tissue constructs, and induce active contraction in engineered skeletal muscle. The vast majority of engineering approaches in these tissues are scaffold-based, providing interim structure and support to engineered constructs, and sufficient integrity to withstand mechanical loading. Alternatively, some recent studies have employed developmentally inspired scaffold-free techniques, relying on cellular self-assembly and matrix production to form tissue constructs. Whether utilizing a scaffold or not, incorporation of mechanobiological stimuli has been shown to improve the composition, structure, and biomechanical function of engineered tendon, ligament, and skeletal muscle. Together, these findings highlight the importance of mechanobiology and suggest how it can be leveraged to engineer these tissues and their interfaces, and to create functional multitissue constructs.

scholarly journals Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: In vitro and in vivo assessment of biological performance

2015 ◽  
Vol 12 ◽  
pp. 227-241 ◽  
Author(s):  
Le-Ping Yan ◽  
Joana Silva-Correia ◽  
Mariana B. Oliveira ◽  
Carlos Vilela ◽  
Hélder Pereira ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Osteochondral Tissue ◽  
Biological Performance ◽  
Osteochondral Tissue Engineering ◽  
In Vivo Assessment

scholarly journals An Overview of Tissue Engineering as an Alternative for Toxicity Assessment

2016 ◽  
Vol 19 (1) ◽  
pp. 31 ◽  
Author(s):  
Mathew Garrod ◽  
David Yi San Chau
Keyword(s):  
Tissue Engineering ◽  
Material Selection ◽  
Ex Vivo ◽  
Toxicity Testing ◽  
Toxicity Assessment ◽  
Ageing Population ◽  
Animal Testing ◽  
Accurate Representation ◽  
Material Sciences

Tissue engineering is a multidisciplinary field that combines aspects of biology, material sciences, engineering and medicine - the ultimate goal being able to fabricate replacement tissues and/or organs for an ageing population. However, parallel to this milestone, is the exploitation of the biomimetic constructs as feasible alternatives to in vivo/ex vivo toxicity testing models due to their accurate representation of innate tissue and organs. Herein, we summarise a range of concepts within tissue engineering with a particular emphasis on biological material selection and implications to animal testing. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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