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Enzyme-sensitive hydrogels containing encapsulated chondrocytes are a promising platform for cartilage tissue engineering. However, the growth of neotissue is closely coupled to the degradation of the hydrogel and is further complicated due to the encapsulated cells serving as the enzyme source for hydrogel degradation. To better understand these coupled processes, this study combined experimental and computational methods to analyze the transition from hydrogel to neotissue in a biomimetic MMP-sensitive poly(ethylene glycol) (PEG) hydrogel with encapsulated chondrocytes. A physics-based computational model that describes spatial heterogeneities in cell distribution was used. Experimentally, cell-laden hydrogels were cultured for six weeks under free swelling or subjected daily to one-hour of dynamic compressive loading. Extracellular matrix (ECM) synthesis rates were used as model inputs, and the model was fit to the experimentally determined construct modulus over time for the free swelling condition. Experimentally, ECM accumulation comprising collagen II and aggrecan increased over time concomitant with hydrogel degradation observed by a loss in PEG. Simulations demonstrated rapid degradation in regions of high cell density (i.e., cell clusters) reaching complete degradation by day 13, which facilitated localized ECM growth. Regions of low cell density degraded more slowly, had limited ECM, and led to the decrease in construct modulus during the first two weeks. The primary difference between the two culture environments was greater ECM accumulation in the clusters under free swelling, which facilitated a faster recovery in construct modulus. By 6 weeks the compressive modulus increased 2.5-fold to 107 kPa under free swelling, but dropped 1.6-fold to 26 kPa under loading. In summary, this biomimetic MMP-sensitive hydrogel supports neocartilage growth by facilitating rapid ECM growth within cell clusters, which was followed by slower growth in the rest of the hydrogel. Subtle temporal differences in hydrogel degradation and ECM accumulation, however, had a significant impact on the evolving mechanical properties.
This article was published in the following journal.
Name: Journal of materials chemistry. B
Adventitial fibroblasts (AFs) are major contributors to vascular remodeling and maladaptive cascades associated with arterial disease, where AFs both contribute to and respond to alterations in their ...
In a novel approach, curcumin has been encapsulated inside Poly(Ethylene Oxide)-Block-Poly(Propylene Oxide)-Block-Poly(Ethylene Oxide) (F108) nanocapsules. FTIR spectra have indicated a type of hydrog...
The harmful cyanobacteria blooms which usually form in spring and summer, cause global eutrophication of freshwater and coastal marine ecosystems. This study tried to utilize cyanobacteria as a raw ma...
Transforming growth factor-β (TGF-β) is a major regulator of extracellular matrix (ECM) events, particularly collagen production.
To investigate the features of expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the matrix metalloproteinase MMP-1 in the cervix uteri and corpus uteri in cervical squamous c...
Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability and premature...
This study was to assess the distinct expression of matrix metalloproteinase 13,tissue inhibitor of metalloproteinases 3, and calcium-sensing receptor, in human trabecular meshwork between...
The matrix metalloproteinase-9 (MMP-9) is considered to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline has direct MMP-9 inhibiting properties in vitro, and ...
Purpose: To compare the levels of matrix metalloproteinase-1 (MMP-1), MMP-8, MMP-13 and tissue inhibitor of metalloproteinases (TIMPs) in keloid skin tissue with normal skin in the same ...
The primary objective of this study is to assess the sensitivity and specificity of a MMP-1/TIMP-1 ratio equal to 0.24 at study entry to predict wound healing at 12 weeks' follow up visit.
A transmembrane domain-containing matrix metalloproteinase. It is synthesized as an inactive zymogen that is activated by the proteolytic action of PROPROTEIN CONVERTASES. Matrix metalloproteinase 16 plays a direct role in the cleavage of proteins in the pericellular environment. In addition it can function indirectly by enzymatically activating the proprotein form of other MATRIX METALLOPROTEINASES such as the zymogen of MATRIX METALLOPROTEINASE 2.
A transmembrane domain-containing matrix metalloproteinase. It is synthesized as an inactive zymogen that is activated by the action of PROPROTEIN CONVERTASES such as FURIN. Matrix metalloproteinase 14 plays a direct role in the cleavage of proteins in the pericellular environment. In addition it can function indirectly by enzymatically activating the proprotein form of MATRIX METALLOPROTEINASE 15.
A secreted matrix metalloproteinase that is believed to play a role in EXTRACELLULAR MATRIX remodeling and cell fate determination during normal and pathological processes. Matrix metalloproteinase 11 was originally isolated in primary BREAST NEOPLASMS and may be involved in the process of tumorigenesis.
A transmembrane domain-containing matrix metalloproteinase that plays a role in the cleavage of proteins in the pericellular environment. It is synthesized as an inactive zymogen that is activated by the action of ENDOPEPTIDASES such as MATRIX METALLOPROTEINASE 14.
A secreted matrix metalloproteinase that is the predominant proteolytic activity in the enamel matrix. The enzyme has a high specificity for dental enamel matrix protein AMELOGENIN.
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...