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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Automated Decellularization of Musculoskeletal Tissues with High Extracellular Matrix Retention
TL;DR: In this paper , a low-cost open-source platform for automated decellularization of extracellular matrix (ECM)-based materials is presented, which can be adapted to an array of decellularity protocols, with an example parts' list provided by the authors.
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Clinical perspectives for repairing rotator cuff injuries with multi-tissue regenerative approaches
Xu Zhang,Dan-Bing Wang,Zuyong Wang,Samuel K.K. Ling,Patrick Shu-Hang Yung,Rocky S. Tuan,Dai Fei Elmer Ker +6 more
TL;DR: The rotator cuff is a highly integrated complex of bone-tendon-muscle units that when injured, has severe consequences for patients and healthcare systems as mentioned in this paper , which can be addressed by targeted regeneration of multi-tissue units.
Journal ArticleDOI
Long-Term Follow-Up of Synthetic Ligament (Orthotape) Usage in Reconstructive Surgery of the Hand
Shalimar Abdullah,Parminder Singh Gill Narin Singh,Elaine Soh Zi Fan,Amir Adham Ahmad,Nor Hazla Mohd Haflah,Jamari Sapuan +5 more
TL;DR: The high extrusion rate of Orthotape discourages its use in the superficial areas of the hand, including flexor and extensor surfaces of the fingers and hand, and recommends its usage in regions with a thick skin cover such as underneath a flap or in deep areas such as the palm.
Journal ArticleDOI
Nanofiber matrix formulations for the delivery of Exendin-4 for tendon regeneration: In vitro and in vivo assessment
Sama Abdulmalik,Jack Gallo,John Nip,Sara Katebifar,Michael R. Arul,Amir Lebaschi,Lucas N. Munch,J Bartly,Shilpa Choudhary,Ivo Kalajzic,Yeshavanth Kumar Banasavadi-Siddegowdae,Syam P. Nukavarapu,Sangamesh G. Kumbar +12 more
TL;DR: In this paper , a peptide growth factor (exendin-4; Ex-4) was used to enhance a nanofiber matrix in a tendon injury model to avoid burst release and protect the drug.
Journal ArticleDOI
Optimizing Tenogenic Differentiation of Equine Adipose-Derived Mesenchymal Stem Cells (eq-ASC) Using TGFB3 Along with BMP Antagonists
TL;DR: An appropriate in vitro potential of spontaneous tenogenic differentiation of eq- ASCs is revealed that can be improved by simultaneous activation of TGFB and inhibition of osteoinductive signaling pathways.
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