S. Pitkänen, Kaarlo Paakinaho, H. Pihlman, Niina Ahola, M. Hannula, Sanja Asikainen, Mikko Manninen, M. Morelius, P. Keränen, J. Hyttinen, M. Kellomäki, O. Laitinen-Vapaavuori, Susanna Miettinen
{"title":"Characterisation and in vitro and in vivo evaluation of supercritical-CO2-foamed β-TCP/PLCL composites for bone applications.","authors":"S. Pitkänen, Kaarlo Paakinaho, H. Pihlman, Niina Ahola, M. Hannula, Sanja Asikainen, Mikko Manninen, M. Morelius, P. Keränen, J. Hyttinen, M. Kellomäki, O. Laitinen-Vapaavuori, Susanna Miettinen","doi":"10.22203/eCM.v038a04","DOIUrl":"https://doi.org/10.22203/eCM.v038a04","url":null,"abstract":"Most synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable β-tricalciumphosphate/poly(L-lactide-co-ε-caprolactone) (β-TCP/PLCL) composite for bone applications using supercritical CO2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 °C, tested samples returned to 95 % of their original height. Hydrolytic degradation of β-TCP/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, β-TCP/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the β-TCP/PLCL composite. The elastic and highly porous β-TCP/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"38 1","pages":"35-50"},"PeriodicalIF":3.1,"publicationDate":"2019-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42436851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aysegul Atasoy-Zeybek, Alan Ivković, Alan Ivković, Tahsin Beyzadeoglu, A. Onal, Christopher H. Evans, G. T. Kose
{"title":"Paracrine effects of living human bone particles on the osteogenic differentiation of mesenchymal stem cells.","authors":"Aysegul Atasoy-Zeybek, Alan Ivković, Alan Ivković, Tahsin Beyzadeoglu, A. Onal, Christopher H. Evans, G. T. Kose","doi":"10.22203/eCM.v038a02","DOIUrl":"https://doi.org/10.22203/eCM.v038a02","url":null,"abstract":"Bone autografting remains the clinical model of choice for resolving problematic fractures. The precise mechanisms through which the autograft promotes bone healing are unknown. The present study examined the hypothesis that cells within the autograft secrete osteogenic factors promoting the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Particles of human bone (\"chips\") were recovered at the time of joint replacement surgery and placed in culture. Then, conditioned media were added to cultures of human, adipose-derived MSCs under both basal and osteogenic conditions. Contrary to expectation, medium conditioned by bone chips reduced the expression of alkaline phosphatase and strongly inhibited mineral deposition by MSCs cultured in osteogenic medium. Real time PCR revealed the inhibition of collagen type I alpha 1 chain (Col1A1) and osteopontin (OPN) expression. These data indicated that the factors secreted by bone chips inhibited the osteogenic differentiation of MSCs. However, in late cultures, bone morphogenetic protein-2 (BMP-2) expression was stimulated, suggesting the possibility of a delayed, secondary osteogenic effect.","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"38 1","pages":"14-22"},"PeriodicalIF":3.1,"publicationDate":"2019-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.22203/eCM.v038a02","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42307790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V-T Duong, T. Dang, J. Kim, K. Kim, H. Ko, C. Hwang, K. Koo
{"title":"Twelve-day medium pumping into tubular cell-laden scaffold using a lab-made PDMS connector.","authors":"V-T Duong, T. Dang, J. Kim, K. Kim, H. Ko, C. Hwang, K. Koo","doi":"10.22203/eCM.v038a01","DOIUrl":"https://doi.org/10.22203/eCM.v038a01","url":null,"abstract":"In the current study, a method is proposed to supply culture medium into a two-layered cell-laden tubular scaffold in order to enhance cell proliferation, confluence, and viability. The two-layered cell-laden tubular scaffold was made of calcium-alginate mixed with fibroblast cells (NIH/3T3) using a lab-made double- coaxial laminar-flow generator. Afterwards, the tubular scaffold was connected to a syringe pump system using a polydimethylsiloxane (PDMS) micro-connector for long-term cell culture. Three medium pumping conditions were applied and compared: a heart-beat-mimicking pumping (20 µL/s, 1 s period, and 50 % pulse width), a continuous pumping (20 µL/s) and a non-pumping. Non-leaky connections between the tubular scaffolds and the micro-connector outlet were sustained for 13.5 ± 0.83 d in heartbeat-mimicking pumping and 11.8 ± 0.33 d in continuous pumping condition, due to the elasticity of the tubular scaffolds. Importantly, the two pumping conditions resulted in more cell proliferation, confluence, and viability than the non-pumping condition. Furthermore, analysis of newly-produced type-I collagen matrix indicated that the cells under the two pumping conditions formed a tissue-like structure. The proposed technique could further be applied to vascular co-culturing for vascular engineered tissue.","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"38 1","pages":"1-13"},"PeriodicalIF":3.1,"publicationDate":"2019-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.22203/eCM.v038a01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43670853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J M McKinney, T N Doan, L Wang, J Deppen, D S Reece, K A Pucha, S Ginn, R D Levit, N J Willett
{"title":"Therapeutic efficacy of intra-articular delivery of encapsulated human mesenchymal stem cells on early stage osteoarthritis.","authors":"J M McKinney, T N Doan, L Wang, J Deppen, D S Reece, K A Pucha, S Ginn, R D Levit, N J Willett","doi":"10.22203/eCM.v037a04","DOIUrl":"https://doi.org/10.22203/eCM.v037a04","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) represent a great therapeutic promise in pre-clinical models of osteoarthritis (OA), but many questions remain as to their therapeutic mechanism of action: engraftment versus paracrine action. Encapsulation of human MSCs (hMSCs) in sodium alginate microspheres allowed for the paracrine signaling properties of these cells to be isolated and studied independently of direct cellular engraftment. The objective of the present study was to quantitatively assess the efficacy of encapsulated hMSCs as a disease-modifying therapeutic for OA, using a medial meniscal tear (MMT) rat model. It was hypothesized that encapsulated hMSCs would have a therapeutic effect, through paracrine-mediated action, on early OA development. Lewis rats underwent MMT surgery to induce OA. 1 d post-surgery, rats received intra-articular injections of encapsulated hMSCs or controls (i.e., saline, empty capsules, non-encapsulated hMSCs). Microstructural changes in the knee joint were quantified using equilibrium partitioning of a ionic contrast agent based micro-computed tomography (EPIC-μCT) at 3 weeks post-surgery, an established time point for early OA. Encapsulated hMSCs significantly attenuated MMT-induced increases in articular cartilage swelling and surface roughness and augmented cartilaginous and mineralized osteophyte volumes. Cellular encapsulation allowed to isolate the hMSC paracrine signaling effects and demonstrated that hMSCs could exert a chondroprotective therapeutic role on early stage OA through paracrine signaling alone. In addition to this chondroprotective role, encapsulated hMSCs augmented the compensatory increases in osteophyte formation. The latter should be taken into strong consideration as many clinical trials using MSCs for OA are currently ongoing.</p>","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"37 ","pages":"42-59"},"PeriodicalIF":3.1,"publicationDate":"2019-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.22203/eCM.v037a04","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10092711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R Hartman, P Patil, R Tisherman, C St Croix, L J Niedernhofer, P D Robbins, F Ambrosio, B Van Houten, G Sowa, N Vo
{"title":"Age-dependent changes in intervertebral disc cell mitochondria and bioenergetics.","authors":"R Hartman, P Patil, R Tisherman, C St Croix, L J Niedernhofer, P D Robbins, F Ambrosio, B Van Houten, G Sowa, N Vo","doi":"10.22203/eCM.v036a13","DOIUrl":"10.22203/eCM.v036a13","url":null,"abstract":"<p><p>Robust cellular bioenergetics is vital in the energy-demanding process of maintaining matrix homeostasis in the intervertebral disc. Age-related decline in disc cellular bioenergetics is hypothesised to contribute to the matrix homeostatic perturbation observed in intervertebral disc degeneration. The present study aimed to measure how ageing impacted disc cell mitochondria and bioenergetics. Age-related changes measured included matrix content and cellularity in disc tissue, as well as matrix synthesis, cell proliferation and senescence markers in cell cultures derived from annulus fibrosus (AF) and nucleus pulposus (NP) isolated from the discs of young (6-9 months) and older (36-50 months) New Zealand White rabbits. Cellular bioenergetic parameters were measured using a Seahorse XFe96 Analyzer, in addition to quantitating mitochondrial morphological changes and membrane potential. Ageing reduced mitochondrial number and membrane potential in both cell types. Also, it significantly reduced glycolytic capacity, mitochondrial reserve capacity, maximum aerobic capacity and non-glucose-dependent respiration in NP. Moreover, NP cells exhibited age-related decline in matrix synthesis and reduced cellularity in older tissues. Despite a lack of changes in mitochondrial respiration with age, AF cells showed an increase in glycolysis and altered matrix production. While previous studies report age-related matrix degenerative changes in disc cells, the present study revealed, for the first time, that ageing affected mitochondrial number and function, particularly in NP cells. Consequently, age-related bioenergetic changes may contribute to the functional alterations in aged NP cells that underlie disc degeneration.</p>","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"36 ","pages":"171-183"},"PeriodicalIF":3.2,"publicationDate":"2018-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/21/a8/nihms-1866644.PMC9972500.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10783877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V Fischer, M Haffner-Luntzer, M Amling, A Ignatius
{"title":"Calcium and vitamin D in bone fracture healing and post-traumatic bone turnover.","authors":"V Fischer, M Haffner-Luntzer, M Amling, A Ignatius","doi":"10.22203/eCM.v035a25","DOIUrl":"https://doi.org/10.22203/eCM.v035a25","url":null,"abstract":"<p><p>Calcium and vitamin D are essential for maintaining bone health. Therefore, deficiencies in calcium and vitamin D are major risk factors for osteoporosis development. Because sufficient amounts of calcium are also required for fracture-callus mineralisation, compromised bone repair that is frequently observed in osteoporotic patients might be attributed to calcium and vitamin D deficiencies. Consequently, calcium and vitamin D supplementation represents a potential strategy for treating compromised fracture healing in osteoporotic patients. Growing clinical evidence suggests that a fracture event may induce post-traumatic bone loss in the non-fractured skeleton, particularly in osteoporotic patients, which might further exacerbate osteoporosis and increase the risk of secondary fractures. Because the skeleton represents the main source of calcium, which is increasingly required during fracture-callus mineralisation, post-traumatic calcium mobilisation might occur under conditions of insufficient calcium and vitamin D status. However, to date, investigations of the roles of calcium and vitamin D in bone repair and post-traumatic bone turnover are very limited. The current review summarises the state of the literature, focusing on the role of calcium and vitamin D in fracture healing and post-traumatic bone turnover, and critically discusses the therapeutic potential of calcium and vitamin D supplementation in this context.</p>","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"35 ","pages":"365-385"},"PeriodicalIF":3.1,"publicationDate":"2018-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.22203/eCM.v035a25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36248519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C S Chang, C Y Yang, H Y Hsiao, L Chen, I M Chu, M H Cheng, C H Tsao
{"title":"Cultivation of auricular chondrocytes in poly(ethylene glycol)/poly(ε-caprolactone) hydrogel for tracheal cartilage tissue engineering in a rabbit model.","authors":"C S Chang, C Y Yang, H Y Hsiao, L Chen, I M Chu, M H Cheng, C H Tsao","doi":"10.22203/eCM.v035a24","DOIUrl":"https://doi.org/10.22203/eCM.v035a24","url":null,"abstract":"<p><p>Tissue engineering has the potential to overcome the limitations of tracheal reconstruction. To tissue-engineer a tracheal cartilage, auricular chondrocytes were encapsulated in a photocurable poly(ethylene glycol)/poly(ε-caprolactone) (PEG/PCL) hydrogel. Chondrogenic genes, including Sox9, Acan and Col2a1, were up-regulated in auricular chondrocytes after 2 weeks of in vitro cultivation in the PEG/PCL hydrogel. Co-cultivation of 70 % auricular chondrocytes and 30 % bone marrow mesenchymal stem cells (BMSCs) accelerated the chondrogenic genes' expression in the PEG/PCL hydrogel. Cartilaginous matrix markers, including proteoglycans and collagen type II, were detected in the chondrocytes-encapsulated PEG/PCL hydrogel after 4 weeks of in vitro cultivation. The higher expression level of cartilaginous matrix markers was observed in the PEG/PCL hydrogel with co-cultivation of 70 % chondrocytes and 30 % BMSCs. After 4 weeks of ectopic cultivation in rabbits, the cylindrical PEG/PCL structure was sustained with the use of a luminal silicon stent. However, without the stent, the construct collapsed under a compression force. No fibrosis or vessel ingrowth were found in the PEG/PCL hydrogel after 4 weeks of ectopic cultivation, whereas the auricular chondrocytes showed proteoglycans' accumulation and collagen type II production. Rabbit auricular chondrocytes could survive and retain chondrogenic ability in the PEG/PCL hydrogel under both in vitro and in vivo conditions. While the PEG/PCL hydrogel did not show sufficient mechanical properties for supporting the cylindrical shape of the construct, the high chondrogenesis level of chondrocytes in the PEG/PCL hydrogel displayed the potential of this material for tracheal tissue engineering.</p>","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"35 ","pages":"350-364"},"PeriodicalIF":3.1,"publicationDate":"2018-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.22203/eCM.v035a24","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36242179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Majewski, P Heisterbach, C Jaquiéry, L Dürselen, A Todorov, I Martin, C H Evans, S A Müller
{"title":"Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model.","authors":"M Majewski, P Heisterbach, C Jaquiéry, L Dürselen, A Todorov, I Martin, C H Evans, S A Müller","doi":"10.22203/eCM.v035a22","DOIUrl":"https://doi.org/10.22203/eCM.v035a22","url":null,"abstract":"<p><p>Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFβ1) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery. After 1, 2, 4 and 8 weeks, healing was assessed based on tendon length and thickness, mechanical strength, stiffness and histology. Best results were achieved when GFs were loaded onto a collagen sponge - with a rapid increase in mechanical strength (load to failure, 71.2 N vs. 7.7 N in controls), consistent tendon length over time (9.9 mm vs. 16.2 mm in controls) and faster tendon remodelling, as measured by histology - followed by tiered injection therapy over 96 h. In conclusion, implantation of a GF-loaded collagen sponge could provide a promising treatment, especially in high-performance athletes and revision cases prone to re-rupture. For conservative treatment, tiered percutaneous GF application could be an option for improving clinical outcome.</p>","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"35 ","pages":"318-334"},"PeriodicalIF":3.1,"publicationDate":"2018-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.22203/eCM.v035a22","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36218226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B J Klotz, K S Lim, Y X Chang, B G Soliman, I Pennings, F P W Melchels, T B F Woodfield, A J Rosenberg, J Malda, D Gawlitta
{"title":"Engineering of a complex bone tissue model with endothelialised channels and capillary-like networks.","authors":"B J Klotz, K S Lim, Y X Chang, B G Soliman, I Pennings, F P W Melchels, T B F Woodfield, A J Rosenberg, J Malda, D Gawlitta","doi":"10.22203/eCM.v035a23","DOIUrl":"https://doi.org/10.22203/eCM.v035a23","url":null,"abstract":"<p><p>In engineering of tissue analogues, upscaling to clinically-relevant sized constructs remains a significant challenge. The successful integration of a vascular network throughout the engineered tissue is anticipated to overcome the lack of nutrient and oxygen supply to residing cells. This work aimed at developing a multiscale bone-tissue-specific vascularisation strategy. Engineering pre-vascularised bone leads to biological and fabrication dilemmas. To fabricate channels endowed with an endothelium and suitable for osteogenesis, rather stiff materials are preferable, while capillarisation requires soft matrices. To overcome this challenge, gelatine-methacryloyl hydrogels were tailored by changing the degree of functionalisation to allow for cell spreading within the hydrogel, while still enabling endothelialisation on the hydrogel surface. An additional challenge was the combination of the multiple required cell-types within one biomaterial, sharing the same culture medium. Consequently, a new medium composition was investigated that simultaneously allowed for endothelialisation, capillarisation and osteogenesis. Integrated multipotent mesenchymal stromal cells, which give rise to pericyte-like and osteogenic cells, and endothelial-colony-forming cells (ECFCs) which form capillaries and endothelium, were used. Based on the aforementioned optimisation, a construct of 8 × 8 × 3 mm, with a central channel of 600 µm in diameter, was engineered. In this construct, ECFCs covered the channel with endothelium and osteogenic cells resided in the hydrogel, adjacent to self-assembled capillary-like networks. This study showed the promise of engineering complex tissue constructs by means of human primary cells, paving the way for scaling-up and finally overcoming the challenge of engineering vascularised tissues.</p>","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"35 ","pages":"335-348"},"PeriodicalIF":3.1,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.22203/eCM.v035a23","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36197424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D M Varma, H A Lin, R G Long, G T Gold, A C Hecht, J C Iatridis, S B Nicoll
{"title":"Thermoresponsive, redox-polymerized cellulosic hydrogels undergo in situ gelation and restore intervertebral disc biomechanics post discectomy.","authors":"D M Varma, H A Lin, R G Long, G T Gold, A C Hecht, J C Iatridis, S B Nicoll","doi":"10.22203/eCM.v035a21","DOIUrl":"10.22203/eCM.v035a21","url":null,"abstract":"<p><p>Back and neck pain are commonly associated with intervertebral disc (IVD) degeneration. Structural augmentation of diseased nucleus pulposus (NP) tissue with biomaterials could restore degeneration-related IVD height loss and degraded biomechanical behaviors; however, effective NP replacement biomaterials are not commercially available. This study developed a novel, crosslinked, dual-polymer network (DPN) hydrogel comprised of methacrylated carboxymethylcellulose (CMC) and methylcellulose (MC), and used in vitro, in situ and in vivo testing to assess its efficacy as an injectable, in situ gelling, biocompatible material that matches native NP properties and restores IVD biomechanical behaviors. Thermogelling MC was required to enable consistent and timely gelation of CMC in situ within whole IVDs. The CMC-MC hydrogel was tuned to match compressive and swelling NP tissue properties. When injected into whole IVDs after discectomy injury, CMC-MC restored IVD height and compressive biomechanical behaviors, including range of motion and neutral zone stiffness, to intact levels. Subcutaneous implantation of the hydrogels in rats further demonstrated good biocompatibility of CMC-MC with a relatively thin fibrous capsule, similar to comparable biomaterials. In conclusion, CMC-MC is an injectable, tunable and biocompatible hydrogel with strong potential to be used as an NP replacement biomaterial since it can gel in situ, match NP properties, and restore IVD height and biomechanical function. Future investigations will evaluate herniation risk under severe loading conditions and assess long-term in vivo performance.</p>","PeriodicalId":11849,"journal":{"name":"European cells & materials","volume":"35 ","pages":"300-317"},"PeriodicalIF":3.2,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/c9/nihms974462.PMC6016390.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36174110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}