Therapeutic Strategies for Tendon Healing Based on Novel Biomaterials, Factors and Cells

Groß, Gerhard; Hoffmann, Andrea

doi:10.1159/000347059

Cited by 364 publications

(28 citation statements)

References 46 publications

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“…The main constituent of the tendon extracellular matrix is collagen. Collagen type I accounts for nearly 95% of the total content of the matrix, and the remaining 5% is formed from collagen types III, V, VI, XII, and XIV [50–52]. Controversial studies on the effect of PRP on collagen expression in tenocytes have been reported, and in some of those studies the expression of collagen types I and III seems to be induced [35].…”

Section: Resultsmentioning

confidence: 99%

Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte BehaviorIn Vitro

Giusti

D’Ascenzo

Mancò

et al. 2014

BioMed Research International

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Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP) seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon healing. The different platelet concentrations tested (up to 5 × 106 plt/µL) stimulated differently tenocytes behavior; intermediate concentrations (0.5 × 106, 1 × 106 plt/µL) strongly induced all tested processes (proliferation, migration, collagen, and MMPs production) if compared to untreated cells; on the contrary, the highest concentration had inhibitory effects on proliferation and strongly reduced migration abilities and overall collagen production but, at the same time, induced increasing MMP production, which could be counterproductive because excessive proteolysis could impair tendon mechanical stability. Thus, these in vitro data strongly suggest the need for a compromise between extremely high and low platelet concentrations to obtain an optimal global effect when inducing in vivo tendon healing.

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Section: Resultsmentioning

confidence: 99%

Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte BehaviorIn Vitro

Giusti

D’Ascenzo

Mancò

et al. 2014

BioMed Research International

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“…Conversely, an isoform of scleraxis (SCX), a critical transcription factor in tendon development [74], was reduced in old tendon. In addition, the reduced expression in old tendon of EGR2 and AS EGR1, both of which are required for tendon differentiation [75], may affect tendon repair [76]. …”

Section: Discussionmentioning

confidence: 99%

“…It is hypothesised that pseudogenes act as post-transcriptional regulators of the corresponding parental gene [74]. In other studies, pseudogenes have been identified as increasing with age, such as pseudogene cyclin D2 in the ovary [76], and recent work has indicated that they may have a role in inflammation [77]. This provides an exciting new frontier to explore in ageing research, and further work is required to determine whether any of the pseudogenes identified in this study have functional significance.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of ageing in uninjured human Achilles tendon

et al. 2015

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IntroductionThe risk of tendon injury and disease increases significantly with increasing age. The aim of the study was to characterise transcriptional changes in human Achilles tendon during the ageing process in order to identify molecular signatures that might contribute to age-related degeneration.MethodsRNA for gene expression analysis using RNA-Seq and quantitative real-time polymerase chain reaction analysis was isolated from young and old macroscopically normal human Achilles tendon. RNA sequence libraries were prepared following ribosomal RNA depletion, and sequencing was undertaken by using the Illumina HiSeq 2000 platform. Expression levels among genes were compared by using fragments per kilobase of exon per million fragments mapped. Differentially expressed genes were defined by using Benjamini-Hochberg false discovery rate approach (P <0.05, expression ratios 1.4 log2 fold change). Alternative splicing of exon variants were also examined by using Cufflinks. The functional significance of genes that showed differential expression between young and old tendon was determined by using ingenuity pathway analysis.ResultsIn total, the expression of 325 transcribed elements, including protein-coding transcripts and non-coding transcripts (small non-coding RNAs, pseudogenes, long non-coding RNAs and a single microRNA), was significantly different in old compared with young tendon (±1.4 log2 fold change, P <0.05). Of these, 191 were at higher levels in older tendon and 134 were at lower levels in older tendon. The top networks for genes differentially expressed with tendon age were from cellular function, cellular growth, and cellular cycling pathways. Notable differential transcriptome changes were also observed in alternative splicing patterns. Several of the top gene ontology terms identified in downregulated isoforms in old tendon related to collagen and post-translational modification of collagen.ConclusionsThis study demonstrates dynamic alterations in RNA with age at numerous genomic levels, indicating changes in the regulation of transcriptional networks. The results suggest that ageing is not primarily associated with loss of ability to synthesise matrix proteins and matrix-degrading enzymes. In addition, we have identified non-coding RNA genes and differentially expressed transcript isoforms of known matrix components with ageing which require further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0544-2) contains supplementary material, which is available to authorized users.

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“…Moreover, donor site is the additional wound and systemic stress factor . This clinical problem might be solved by biovital skin substitutes obtained by tissue engineering methods . The essence of the method is to use elements of allogeneic dermis extracellular matrix as a scaffold for in vitro cultured autologous fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

“…2 This clinical problem might be solved by biovital skin substitutes obtained by tissue engineering methods. [3][4][5] The essence of the method is to use elements of allogeneic dermis extracellular matrix as a scaffold for in vitro cultured autologous fibroblasts. Insertion of a scaffold into a newly formatted tissue provides mechanical protection against in vivo occurring forces until the grafted skin substitute will become an integral element of the body.…”

Section: Introductionmentioning

confidence: 99%

Atomic force microscopy in the production of a biovital skin graft based on human acellular dermal matrix produced in‐house and in vitro cultured human fibroblasts

et al. 2017

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The most efficient method in III° burn treatment is the use of the autologous split thickness skin grafts that were donated from undamaged body area. The main limitation of this method is lack of suitable donor sites. Tissue engineering is a useful tool to solve this problem. The goal of this study was to find the most efficient way of producing biovital skin substitute based on in house produced acellular dermal matrix ADM and in vitro cultured fibroblasts. Sixty samples of sterilized human allogeneic skin (that came from 10 different donors) were used to examine the influence of decellularizing substances on extracellular matrix and clinical usefulness of the test samples of allogeneic human dermis. Six groups of acellular dermal matrix were studied: ADM-1 control group, ADM-2 research group (24 h incubation in 0.05% trypsin/EDTA solution), ADM-3 research group (24 h incubation in 0.025% trypsin/EDTA solution), ADM-4 research group (24 h incubation in 0.05% trypsin/EDTA solution and 4 h incubation in 0,1% SDS), ADM-5 research group (24 h incubation in 0.025% trypsin/EDTA solution and 4 h incubation in 0,1% SDS), and ADM-6 research group (24 h incubation in 0,1% SDS). Obtained ADMs were examined histochemically and by atomic force microscopy (AFM). ADMs were settled by human fibroblasts. The number of cultured cells and their vitality were measured. The obtained results indicated that the optimal method for production of living skin substitutes is colonization of autologous fibroblasts on the scaffold prepared by the incubation of human allogeneic dermis in 0.05% trypsin/EDTA. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 726-733, 2018.

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Therapeutic Strategies for Tendon Healing Based on Novel Biomaterials, Factors and Cells

Cited by 364 publications

References 46 publications

Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte BehaviorIn Vitro

Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte BehaviorIn Vitro

Transcriptome analysis of ageing in uninjured human Achilles tendon

Atomic force microscopy in the production of a biovital skin graft based on human acellular dermal matrix produced in‐house and in vitro cultured human fibroblasts

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