scholarly journals Fibrin-genipin adhesive hydrogel for annulus fibrosus repair: performance evaluation with large animal organ culture, in situ biomechanics, and in vivo degradation tests

2014 ◽  
Vol 28 ◽  
pp. 25-38 ◽  
Author(s):  
M Likhitpanichkul ◽  
◽  
M Dreischarf ◽  
S Illien-Junger ◽  
BA Walter ◽  
...  
Keyword(s):  
Performance Evaluation ◽  
Organ Culture ◽  
Annulus Fibrosus ◽  
Large Animal ◽  
Degradation Tests ◽  
Animal Organ ◽  
In Vivo Degradation

scholarly journals Fabrication, Crystalline Behavior, Mechanical Property and In-Vivo Degradation of Poly(l–lactide) (PLLA)–Magnesium Oxide Whiskers (MgO) Nano Composites Prepared by In-Situ Polymerization

Polymers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1123 ◽  
Author(s):  
Hui Liang ◽  
Yun Zhao ◽  
Jinjun Yang ◽  
Xiao Li ◽  
Xiaoxian Yang ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Magnesium Oxide ◽  
Bone Repair ◽  
In Situ Polymerization ◽  
Resonance Spectroscopy ◽  
Scanning Calorimetry ◽  
Biomedical Material ◽  
In Vivo Degradation

The present work focuses on the preparation of poly(l–lactide)–magnesium oxide whiskers (PLLA–MgO) composites by the in-situ polymerization method for bone repair and implant. PLLA–MgO composites were evaluated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and solid-state 13C and 1H nuclear magnetic resonance spectroscopy (NMR). It was found that the whiskers were uniformly dispersed in the PLLA matrix through the interfacial interaction bonding between PLLA and MgO; thereby, the MgO whisker was found to be well-distributed in the PLLA matrix, and biocomposites with excellent interface bonding were produced. Notably, the MgO whisker has an effect on the crystallization behavior and mechanical properties; moreover, the in vivo degradation of PLLA–MgO composites could also be adjusted by MgO. These results show that the whisker content of 0.5 wt % and 1.0 wt % exhibited a prominent nucleation effect for the PLLA matrix, and specifically 1.0 wt % MgO was found to benefit the enhanced mechanical properties greatly. In addition, the improvement of the degrading process of the composite illustrated that the MgO whisker can effectively regulate the degradation of the PLLA matrix as well as raise its bioactivity. Hence, these results demonstrated the promising application of PLLA–MgO composite to serve as a biomedical material for bone-related repair.

Hydrogels are promising considering their incredible capacity to modify, encapsulate and co-deliver medicinal compounds, cells, biomolecules, and nanomaterials

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Sol Gel ◽  
Therapeutic Drug ◽  
Large Animal ◽  
Medicinal Compounds ◽  
Hydrogel Matrix ◽  
Therapeutic Molecules ◽  
Sol Gel Transition ◽  
Gel Transition

As many medications are administered jointly, they often give larger benefits, counteract disadvantages, and enhance treatment results compared to monotherapy. Whether natural or synthetic, injectable biomaterials can form degradable networks in situ, decreasing patient pain and cost while presenting new and promising possibilities for minimally invasive surgery. Biomaterials' ability to create and manufacture injectable systems is strongly impacted by their physicochemical and mechanical properties. The design and manufacture of injectable systems containing cells, therapeutic molecules, particles, and biomolecules that can be injected into geometrically complex body tissue regions poses a significant challenge as they must ensure drug/biomolecule/material bioactivity, cell survival and retention. Hydrogels are a promising choice in this case given their amazing ability to manipulate, encapsulate and co-deliver pharmaceutical chemicals, cells, biomolecules, and nanomaterials. Hydrogels can alter their mechanical and deteriorating qualities by adjusting the cross-linking technique and chemical composition. The ability to modify IH's mechanical strength permits co-encapsulation of medicinal compounds, cells, nanomaterials, and growth factors in the matrix in situ, allowing for multimodal synergistic therapies.To boost the prospects of translating IHs into normal clinics, various barriers and outstanding scientific issues must be tackled in the future. Future investigations, including the application of IHs in multimodal synergistic treatment, should start with large animal models such as monkeys and dogs or even ex vivo human tissue models. In addition, the period of in vivo evaluations should be prolonged from weeks to months for trustworthy and accurate data to be translated to clinical trials. On the one hand, the toxicity of certain crosslinking agents used in IH synthesis must be considered, as the residues will cause unwanted in vivo reactions.Toxic crosslinkers, on the other hand, may interact with therapeutic molecules/biomolecules or nanomaterials trapped in the hydrogel matrix, causing loss of bioactivity. Similarly, IHs' sol–gel transition is a vital issue requiring much investigation. A quick sol–gel transition of precursor solutions might cause the fluid to be caught in the needle, whereas high-viscosity precursor solutions need high injection force, resulting in physician hand fatigue and patient annoyance. Other concerns for clinical IH translation include fast release and rate of degradation. Degradation rate is critical in controlling therapeutic drug release and tissue regeneration. Fast hydrogel breakdown may trigger early inflammatory reaction due to breakdown products, whereas delayed degradation may result in insufficient release of therapeutic drugs. Changing the composition, structure, and crystallinity of polymers must be employed to customize the breakdown rate. Expert researchers will be better equipped to tackle these challenges if they have a deeper knowledge of polymers' physiochemical features. Overall, future IH design should focus on building simple, well-defined 3D networks with low toxicity, high biodegradation rate, and acceptable functionality.

scholarly journals Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

2014 ◽  
Vol 14 (11) ◽  
pp. 2724-2732 ◽  
Author(s):  
Svenja Illien-Jünger ◽  
Young Lu ◽  
Devina Purmessur ◽  
Jillian E. Mayer ◽  
Benjamin A. Walter ◽  
...  
Keyword(s):  
Growth Factor ◽  
Intervertebral Disc ◽  
Organ Culture ◽  
Large Animal ◽  
Culture Model ◽  
Animal Organ ◽  
Growth Factor Treatment

Development of a System for Application of Dynamic Mechanical Compression on Intervertebral Discs in Organ Culture and Investigation of Load Magnitude Effects

2007 ◽  
Author(s):  
Casey L. Korecki ◽  
Jeffrey J. MacLean ◽  
James C. Iatridis
Keyword(s):  
Organ Culture ◽  
Intervertebral Discs ◽  
Small Sample ◽  
In Vivo Studies ◽  
Large Animal Model ◽  
Large Animal ◽  
In Vivo Models ◽  
Compression Loading ◽  
Dynamic Mechanical

In vivo studies on the intervertebral disc (IVD) indicate that the magnitude, frequency, and duration of applied compression loading results in alterations in mRNA expression, composition, and annulus fibrosus structure [1]. In vivo models typically use small animal models or small sample sizes that make it difficult to evaluate multiple dependent variables on the same tissue. In this study, it was considered a priority to utilize a large animal model to investigate the effects of magnitude of compression loading on interacting dependent variable measurements of disc cell viability, biosynthesis, composition, structure, and biomechanics. A bovine IVD organ culture system was used because it provides control over mechanical and chemical boundary conditions while maintaining viable cells and normal cell-matrix interactions. To date, there are no studies investigating the response of the IVD in organ culture to dynamic mechanical loading.

Asymmetric Loading Promotes Early Signs of Intervertebral Disc Degeneration in Large Animal Organ Culture

2009 ◽  
Author(s):  
Casey L. Korecki ◽  
Benjamin A. Walter ◽  
Karolyn E. Godburn ◽  
James C. Iatridis
Keyword(s):  
Animal Models ◽  
Intervertebral Disc ◽  
Organ Culture ◽  
Biological Response ◽  
In Vivo Studies ◽  
Large Animal ◽  
Large Animal Models ◽  
Bending Loads ◽  
Ivd Degeneration

Intervertebral disc (IVD) degeneration is a complex pathology, involving alterations in mechanical and biological function. Mechanical injury to IVDs may contribute to the development of IVD degeneration, and can arise following excessive loading or repeated exposure to loading levels which are not instantaneously damaging. Lateral bending and flexion produced the highest maximum shear strains in human IVDs and are considered the motions that place the IVD at greatest risk of injury (1). The biological response of the IVD to combined bending and compression has been examined in vivo in rat and mouse tail bending models demonstrating structural disruption, apoptosis and remodeling (2,4). However, there are practical limitations to current in vivo studies, as it can be difficult to apply repeated bending loads to the disc in vivo, and few large animal models exist capable of tracking the early biological, structural and compositional changes from asymmetrical loading. IVD organ culture allows control over mechanical boundary conditions and investigation of cellular responses to loading while the IVD remains largely intact, and allows the use of large animal models which more closely mimic the nutritional and compositional nature of human IVDs.

Apparatus to Determine the Macroscopic and Microscopic Biaxial Swelling Response of the Annulus Fibrosus

2002 ◽  
Author(s):  
Paul Hulme ◽  
Sabina Bruehlmann ◽  
Neil A. Duncan
Keyword(s):  
Annulus Fibrosus ◽  
Biaxial Loading ◽  
Mechanical Response ◽  
Swelling Behaviour ◽  
Vertebral Bodies ◽  
And Control ◽  
Bearing Structure ◽  
Outer Annulus Fibrosus

The intervertebral disc (IVD) is a “hydrostatic load-bearing structure” [1], found between the vertebral bodies of the spine. The IVD is composed of the inner and outer annulus fibrosus and a gelatinous center, the nucleus pulposus. Fluid is the largest component of the IVD. Swelling affects the macroscopic mechanical response of the tissue, as well as the microscopic nutrient and solute transport to the cells of the IVD. Previous studies describing the macroscopic swelling behaviour of the annulus fibrosus have been uniaxial in nature [2,3]. However, the behaviour of the annulus is markedly affected by its geometry [3]. By examining a biaxial section of annulus fibrosus with a portion of the bone attachment present, the structure of the annular test section will be maintained and by inference so should its function [4]. Therefore, the objective of this study was to develop an apparatus to investigate simultaneously both the macroscopic and microscopic swelling behaviour of the annulus fibrosus subjected to realistic biaxial loading. The biaxial loading device should maintain the annulus fibrosus in vivo geometry and environment, monitor stress and control tissue strain, while positioning the tissue in a manner that allows for in situ visualization of the cells.

scholarly journals Novel Threadlike Structures May Be Present on the Large Animal Organ Surface: Evidence in Swine Model

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Kyoung-Hee Bae ◽  
Sang Hyun Park ◽  
Byung-Cheon Lee ◽  
Min-Ho Nam ◽  
Ji Woong Yoon ◽  
...  
Keyword(s):  
Trypan Blue ◽  
Polarized Light ◽  
Optical Microscope ◽  
Blue Staining ◽  
Swine Model ◽  
Large Animal ◽  
Dapi Staining ◽  
Trypan Blue Staining ◽  
Animal Organ

Background. The types of embryonic development probably provoke different paths of novel threadlike structure (NTS) development. The authors hypothesized that NTS may be easily observed on the surface of swine intestines by using trypan blue staining method and visualization under an optical microscope.Methods. General anesthesia was administered to 2 Yorkshire pigs. The abdominal walls of the pigs were carefully dissected along the medial alba. NTSs were identified on organ surfaces under a stereoscopic microscope after trypan blue staining. Isolated NTS specimens obtained from the large intestine were subjected to 4′,6-diamidino-2-phenylindole (DAPI) staining and observed using the polarized light microscopy to confirm whether the obtained structure fits the definition of NTS.Results. We found elastic, semitransparent threadlike structures (forming a network structure) that had a milky-white colorin situandin vivoin swine large intestines. The samples showed distinct extinction of polarized light at every 90 degrees, and nucleus was shown to be rod shaped by DAPI staining, indicating that they meet the criteria of NTS.Conclusion. We used a swine model to demonstrate that NTS may be present on large animal organ surfaces. Our results may permit similar studies by using human specimens.

scholarly journals Mesenchymal Stem Cells Delivered in a Novel Cartilage Mimetic Hydrogel for the Treatment of Focal Chondral Lesions in an Equine Animal Model

2019 ◽  
Vol 7 (7_suppl5) ◽  
pp. 2325967119S0028
Author(s):  
Cecilia Pascual-Garrido ◽  
Francisco Rodriguez-Fontan ◽  
Masahiko Haneda ◽  
Elizabeth Aisenbrey ◽  
Karin Payne ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cartilage Repair ◽  
Poor Quality ◽  
Quality Score ◽  
Compressive Modulus ◽  
Large Animal ◽  
Osteochondral Defects

Objectives: A degradable biomaterial has been developed that resembles the native cartilage biochemical properties, in which stem cells can be seeded, differentiate and develop cartilaginous tissue. The purposes of this study were: 1) to determine if mesenchymal stem cells (MSCs) embedded in this cartilage mimetic hydrogel display in vitro chondrogenesis; 2) to demonstrate that the proposed hydrogel can be delivered in situ; and 3) to determine if the hydrogel ± MSCs supports in vivo chondrogenesis. Methods: A photopolymerizable hydrogel consisting of polyethylene glycol, CVPLSLYSGC, chondroitin sulfate (ChS), CRGDS and TGF-β3 was used. Equine bone marrow-derived MSCs were encapsulated in the hydrogel and cultured for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6 and 9. Chondrogenic differentiation was investigated via qPCR, Safranin-O staining and immunofluorescence. Three female horses were used. Two 15-mm width x 5-mm depth osteochondral defects were created bilaterally in the medial femoral condyle of each stifle joint. Five groups were established: Hydrogel (n=3), Hydrogel + MSCs (n=3), Microfracture (MFX, n=1), MFX + Hydrogel (n=3), and MFX + Hydrogel + MSCs (n=2). Repair tissue was evaluated at 6 months post intervention with the following cartilage repair scoring systems: macroscopically, International Cartilage Repair Society (ICRS); and histologically, the Modified O’Driscoll scoring (MODS) and ICRS II (Overall assessment 0%, fibrous -100%, hyaline cartilage).The ICRS parameter is scored using a 100-mm VAS, a score of 0 was assigned for properties considered indicative of poor quality and 100 for good quality. Results: In vitro, there was a significant increase in compressive modulus, collagen II and ChS as confirmation of chondrogenesis and hydrogel degradation. (Figure 1) In vivo, the hydrogel was readily photopolimerized in the defect. Cartilage repair was evident in all groups. As shown in Table 1, red indicates best quality score, blue means a poor quality score, but there was no statistical difference. According to the macroscopic ICRS, the hydrogel + MSCs performed better (P= 0.47). However, the MFX + Hydrogel + MSCs tended to perform better per the MODS (P= 0.61); and ICRS-Overall assessment (P= 0.9). Particularly, MFX showed the lowest score for subchondral bone(SCB) abnormalities (0% = abnormal, P= 0.09) but no inflammation was evident (100% = absent, P= 0.53), whereas the Hydrogel had the highest basal integration (100% = complete integration, P= 0.38) but presented moderate inflammation (Figure 2A). MFX showed SCB abnormalities and vascularization (Figure 2 B). Interestingly, a defect treated with MFX + Hydrogel presented more GAGs, less inflammation (vs Hydrogel) and less SCB abnormalities (vs MFX) (Figure 2C). Overall, the group performing better was MFX + Hydrogel + MSCs. Conclusion: This pilot study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a large animal model. The presence of all three balanced factors (MFX, Hydrogel, MSCs) had higher scores per MODS summation and ICRS Overall assessment. Strengths of this study include: comparison of standard MFX therapy of osteochondral defects with a novel cartilage mimetic therapy; and use of a large animal that resembles the human knee biomechanically and anatomically. [Figure: see text][Figure: see text][Table: see text]

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