Tissue-specific extracellular matrix scaffolds for the regeneration of spatially complex musculoskeletal tissues

Cunniffe, Gráinne M.; Díaz-Payno, Pedro J.; Sheehy, Eamon J.; Critchley, Susan E.; Almeida, Henrique V.; Pitacco, Pierluca; Carroll, Simon F.; Mahon, Olwyn R.; Dunne, Aisling; Levingstone, Tanya J.; Moran, Conor; Brady, Robert T.; O’Brien, Fergal J.; Brama, P. A. J.; Kelly, Daniel J.

doi:10.1016/j.biomaterials.2018.09.044

Cited by 103 publications

(74 citation statements)

References 69 publications

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“…In contrast with an almost generalized use of macroscopic and microscopic scores (mainly ICRS score and O'Driscoll score) and histological analyses, in 7/14 papers, microtomographical assessment is reported, and in 5/14 papers, biomechanical tests are performed; among these, 4/5 were indentation tests and 1/5 compression test. When specified, the site selected for the creation of osteochondral defects was in one case the talus [56], in one paper, the trochlea and the medial condyles [57], and for the other papers, medial condyles [58–62] or both medial and lateral condyles [29, 63–75]. In some cases, the choice of central weight-bearing area was underlined [60, 61, 66, 67].…”

Section: Resultsmentioning

confidence: 99%

Current Trends in the Evaluation of Osteochondral Lesion Treatments: Histology, Histomorphometry, and Biomechanics in Preclinical Models

Maglio

Brogini

Pagani

et al. 2019

BioMed Research International

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Osteochondral lesions (OCs) are typically of traumatic origins but are also caused by degenerative conditions, in primis osteoarthritis (OA). On the other side, OC lesions themselves, getting worse over time, can lead to OA, indicating that chondral and OC defects represent a risk factor for the onset of the pathology. Many animal models have been set up for years for the study of OC regeneration, being successfully employed to test different treatment strategies, from biomaterials and cells to physical and biological adjuvant therapies. These studies rely on a plethora of post-explant investigations ranging from histological and histomorphometric analyses to biomechanical ones. The present review aims to analyze the methods employed for the evaluation of OC treatments in each animal model by screening literature data within the last 10 years. According to the selected research criteria performed in two databases, 60 works were included. Data revealed that lapine (50% of studies) and ovine (23% of studies) models are predominant, and knee joints are the most used anatomical locations for creating OC defects. Analyses are mostly conducted on paraffin-embedded samples in order to perform histological/histomorphometric analyses by applying semiquantitative scoring systems and on fresh samples in order to perform biomechanical investigations by indentation tests on articular cartilage. Instead, a great heterogeneity is pointed out in terms of OC defect dimensions and animal's age. The choice of experimental times is generally adequate for the animal models adopted, although few studies adopt very long experimental times. Improvements in data reporting and in standardization of protocols would be desirable for a better comparison of results and for ethical reasons related to appropriate and successful animal experimentation.

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Section: Resultsmentioning

confidence: 99%

Current Trends in the Evaluation of Osteochondral Lesion Treatments: Histology, Histomorphometry, and Biomechanics in Preclinical Models

Maglio

Brogini

Pagani

et al. 2019

BioMed Research International

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“…Xenogeneic extracellular matrix (ECM)‐derived biological scaffolds have been used in a variety of clinical indications, promoting tissue repair by providing both structural and functional cues to resident cells (Badylak, ; Badylak, Freytes, & Gilbert, ). ECM scaffolds fabricated from decellularized animal or human AC tissue are promising biomaterials for AC regeneration due to their inherent chondro‐inductivity (Almeida et al, , ; Almeida, Eswaramoorthy, et al, ; Beck, Barragan, Libeer, et al, ; Beck, Barragan, Tadros, Gehrke, & Detamore, ; Benders et al, ; Cheng, Estes, Awad, & Guilak, ; Cunniffe et al, ; Gawlitta et al, ; Sutherland, Beck, et al, ; Sutherland, Converse, Hopkins, & Detamore, ; Vindas Bolaños et al, ; Yang et al, ). Such biological scaffolds typically take one of two forms.…”

Section: Introductionmentioning

confidence: 99%

Glyoxal cross‐linking of solubilized extracellular matrix to produce highly porous, elastic, and chondro‐permissive scaffolds for orthopedic tissue engineering

Browe

Mahon

Díaz-Payno

et al. 2019

J Biomedical Materials Res

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Extracellular matrix (ECM)-derived implants hold great promise for tissue repair, but new strategies are required to produce efficiently decellularized scaffolds with the necessary porosity and mechanical properties to facilitate regeneration. In this study, we demonstrate that it is possible to produce highly porous, elastic, articular cartilage (AC) ECM-derived scaffolds that are efficiently decellularized, nonimmunogenic, and chondro-permissive. Pepsin solubilized porcine AC was cross-linked with glyoxal, lyophilized and then subjected to dehydrothermal treatment. The resulting scaffolds were predominantly collagenous in nature, with the majority of sulphated glycosaminoglycan (sGAG) and DNA removed during scaffold fabrication. Four scaffold variants were produced to examine the effect of both ECM (10 or 20 mg/mL) and glyoxal (5 or 10 mM) concentration on the mechanical and biological properties of the resulting construct.When seeded with human infrapatellar fat pad-derived stromal cells, the scaffolds with the lowest concentration of both ECM and glyoxal were found to promote the development of a more hyaline-like cartilage tissue, as evident by increased sGAG and type II collagen deposition. Furthermore, when cultured in the presence of human macrophages, it was found that these ECM-derived scaffolds did not induce the production of key proinflammatory cytokines, which is critical to success of an implantable biomaterial.Together these findings demonstrate that the novel combination of solubilized AC ECM and glyoxal crosslinking can be used to produce highly porous scaffolds that are sufficiently decellularized, highly elastic, chondro-permissive and do not illicit a detrimental immune response when cultured in the presence of human macrophages. K E Y W O R D S cartilage, decellularization, extracellular matrix, immune response, scaffold, tissue engineering

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“…The strategy developed in this study to generate scaled-up osteochondral implants offers several advantages over previous tissue engineering and 3D bioprinting approaches to joint regeneration. As mentioned previously, a number of studies have explored the use of different biphasic and tri-phasic scaffolds for cartilage and osteochondral defect repair 14,[29][30][31][32] . While these approaches are promising for treating focal defects, challenges will arise when attempting to scaleup such approaches up to treat whole articular surfaces.…”

Section: Addressing the Challenge Of Cartilage-bone Region Integratiomentioning

confidence: 99%

Biofabrication of spatially organised tissues by directing the growth of cellular spheroids within 3D printed polymeric microchambers

2019

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Successful tissue engineering requires the generation of human scale implants that mimic the structure, composition and mechanical properties of native tissues. Here, we report a novel biofabrication strategy that enables the engineering of structurally organised tissues by guiding the growth of cellular spheroids within arrays of 3D printed polymeric microchambers. With the goal of engineering stratified articular cartilage, inkjet bioprinting was used to deposit defined numbers of mesenchymal stem cells (MSCs) and chondrocytes into pre-printed microchambers. These jetted cell suspensions rapidly underwent condensation within the hydrophobic microchambers, leading to the formation of organised arrays of cellular spheroids. The microchambers were also designed to provide boundary conditions to these spheroids, guiding their growth and eventual fusion, leading to the development of stratified cartilage tissue with a depth-dependant collagen fiber architecture that mimicked the structure of native articular cartilage. Furthermore, the composition and biomechanical properties of the bioprinted cartilage was also comparable to the native tissue. Using multi-tool biofabrication, we were also able to engineer anatomically accurate, human scale, osteochondral templates by printing this microchamber system on top of a hypertrophic cartilage region designed to support endochondral bone formation and then maintaining the entire construct in long-term bioreactor culture to enhance tissue development. This bioprinting strategy provides a versatile and scalable approach to engineer structurally organised cartilage tissues for joint resurfacing applications.

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Tissue-specific extracellular matrix scaffolds for the regeneration of spatially complex musculoskeletal tissues

Cited by 103 publications

References 69 publications

Current Trends in the Evaluation of Osteochondral Lesion Treatments: Histology, Histomorphometry, and Biomechanics in Preclinical Models

Current Trends in the Evaluation of Osteochondral Lesion Treatments: Histology, Histomorphometry, and Biomechanics in Preclinical Models

Glyoxal cross‐linking of solubilized extracellular matrix to produce highly porous, elastic, and chondro‐permissive scaffolds for orthopedic tissue engineering

Biofabrication of spatially organised tissues by directing the growth of cellular spheroids within 3D printed polymeric microchambers

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