Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm.
TLDR
A greater understanding of the molecular mechanisms involved in T/L development and natural healing, coupled with the capability of producing complex biomaterials to deliver multiple biofactors with high spatiotemporal resolution and specificity, should lead to regenerative procedures that more closely recapitulate T/l morphogenesis.Abstract:
Tendon and ligament (T/L) are dense connective tissues connecting bone to muscle and bone to bone, respectively. Similar to other musculoskeletal tissues, T/L arise from the somitic mesoderm, but they are derived from a recently discovered somitic compartment, the syndetome. The adjacent sclerotome and myotome provide inductive signals to the interposing syndetome, thereby upregulating the expression of the transcription factor Scleraxis, which in turn leads to further tenogenic and ligamentogenic differentiation. These advances in the understanding of T/L development have been sought to provide a knowledge base for improving the healing of T/L injuries, a common clinical challenge due to the intrinsically poor natural healing response. Specifically, the three most common tendon injuries involve tearing of the rotator cuff of the shoulder, the flexor tendon of the hand, and the Achilles tendon. At present, injuries to these tissues are treated by surgical repair and/or conservative approaches, including biophysical modalities such as physical rehabilitation and cryotherapy. Unfortunately, the healing tissue forms fibrovascular scar and possesses inferior mechanical and biochemical properties as compared to native T/L. Therefore, tissue engineers have sought to improve upon the natural healing response by augmenting the injured tissue with cells, scaffolds, bioactive agents, and mechanical stimulation. These strategies show promise, both in vitro and in vivo, for improving T/L healing. However, several challenges remain in restoring full T/L function following injury, including uncertainties over the optimal combination of these biological agents as well how to best deliver tissue engineered elements to the injury site. A greater understanding of the molecular mechanisms involved in T/L development and natural healing, coupled with the capability of producing complex biomaterials to deliver multiple growth factors with high spatiotemporal resolution and specificity, will allow tissue engineers to more closely recapitulate T/L morphogenesis, thereby offering future patients the prospect of T/L regeneration, as opposed to simple tissue repair.read more
Citations
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Journal ArticleDOI
Chemically Modified Messenger RNA: Modified RNA Application for Treatment of Achilles Tendon Defects.
Elmar Herbst,Elmar Herbst,Florian B. Imhoff,Peter Foehr,Stefan Milz,Christian Plank,Carsten Rudolph,Günther Hasenpusch,Johannes Geiger,Manish K. Aneja,Karoline Groth,Stephan Vogt,Andreas B. Imhoff,Andreas Schmitt +13 more
TL;DR: This pilot study demonstrates the feasibility of a novel messenger RNA (mRNA)-based therapy for Achilles tendon defects using chemically modified mRNA coding for bFGF.
DissertationDOI
A physicochemical approach to design bioactive scaffolds for tissue engineering
TL;DR: A submitted manuscript is the version of the article upon submission and before peer-review as mentioned in this paper, while a published version is the final layout of the paper including the volume, issue and page numbers.
Journal ArticleDOI
Complete mid-portion rupture of the rat achilles tendon leads to remote and time-mismatched changes in uninjured regions
Flávio Santos da Silva,Bento João Abreu,Bengt I. Eriksson,Paul W. Ackermann,Paul W. Ackermann +4 more
TL;DR: It is demonstrated that uninjured areas of the AT remote from the rupture site also undergo pronounced remodeling, although with time-span differences relative to injured AT portions, which may have implications in the choice of rehabilitation regimes.
Journal ArticleDOI
Molecular Characteristics of the Equine Periodontal Ligament.
TL;DR: Significantly higher expression levels of COL1 and 3 were found in the mature equine PDL in comparison with mature tendon, indicating higher rates of collagen production and turnover in the maturity equinePDL.
Journal ArticleDOI
Mutations in COMP cause familial carpal tunnel syndrome
Chunyu Li,Ni Wang,Alejandro A. Schäffer,Xilin Liu,Zhuo Zhao,Gene Elliott,Lisa Garrett,Nga Ting Choi,Yueshu Wang,Yufa Wang,Cheng Wang,Jin Wang,Danny Chan,Peiqiang Su,Shusen Cui,Yingzi Yang,Yingzi Yang,Bo Gao,Bo Gao +18 more
TL;DR: Two CTS-related mutations in two large families that impair secretion of COMP in tenocytes, leading to ER stress-induced unfolded protein response, inflammation and fibrosis in patients and mouse models are reported.
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