scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm.

01 Sep 2013-Birth Defects Research Part C-embryo Today-reviews (NIH Public Access)-Vol. 99, Iss: 3, pp 203-222
TL;DR: 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.

Content maybe subject to copyright    Report

Citations
More filters
Book
09 Oct 1998
TL;DR: This poster presents a probabilistic procedure for estimating the mechanical properties of bone based on known mechanisms, including compressive forces, compressive strength, and the compressive properties of Bone.
Abstract: Forces in Joints, Skeletal Biology, Analysis of Bone Remodeling, Mechanical Properties of Bone, Fatigue and Fracture Resistance of Bone, Mechanical Adaptation of the Skeleton, Synovial Joint Mechanics, Mechanical Properties of Ligament and Tendon

1,246 citations


Cites methods from "Tendon and ligament regeneration an..."

  • ...To further explore biological aspects of tendon and ligament development and repair we refer readers to an article by Yang and co-authors entitled: Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm (Birth Defects Research, 2013) (Yang et al. 2013)....

    [...]

Journal ArticleDOI
TL;DR: This review describes and critically assess the current strategies for enhancing tendon repair by biological means, mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage.

478 citations


Cites background from "Tendon and ligament regeneration an..."

  • ...Tendon injury stimulates the production of a variety of growth factors at multiple stages in the healing process [40,42] leading to increased cellularity and tissue volume [47]....

    [...]

Journal ArticleDOI
14 May 2018
TL;DR: An implantable pressure and strain sensor made entirely of biodegradable materials designed to degrade after its useful lifetime is reported, eliminating the need for a second surgery to remove the device.
Abstract: The ability to monitor, in real time, the mechanical forces on tendons after surgical repair could allow personalized rehabilitation programmes to be developed for recovering patients. However, the development of devices capable of such measurements has been hindered by the strict requirements of biocompatible materials and the need for sensors with satisfactory performance. Here we report an implantable pressure and strain sensor made entirely of biodegradable materials. The sensor is designed to degrade after its useful lifetime, eliminating the need for a second surgery to remove the device. It can measure strain and pressure independently using two vertically isolated sensors capable of discriminating strain as small as 0.4% and the pressure exerted by a grain of salt (12 Pa), without them interfering with one another. The device has minimal hysteresis, a response time in the millisecond range, and an excellent cycling stability for strain and pressure sensing, respectively. We have incorporated a biodegradable elastomer optimized to improve the strain cycling performances by 54%. An in vivo study shows that the sensor exhibits excellent biocompatibility and function in a rat model, illustrating the potential applicability of the device to the real-time monitoring of tendon healing.

404 citations

Journal ArticleDOI
TL;DR: How the 3D printing technology can contribute to the improvement of traditional electrospinning technology for the fabrication of 3D electrospun nanofiber materials as drug delivery devices/implants, scaffolds or living tissue constructs is emphasized.

259 citations


Cites background from "Tendon and ligament regeneration an..."

  • ...tissues connecting muscle to bone, and bone to bone, respectively [237]....

    [...]

Journal ArticleDOI
TL;DR: A novel framework to understand tendon physiology and pathophysiology is described that may be useful in pushing the field forward and represents a perspective on the important role that biomaterials will play in translating research discoveries to the patient.

238 citations


Cites background from "Tendon and ligament regeneration an..."

  • ...For instance, experiments on rodents (mice, rats) and rabbits form the basis of much of our controlled experimental knowledge on healing response to injury, yet heal in an accelerated manner that deviates from humans [25,26]....

    [...]

References
More filters
Journal ArticleDOI
TL;DR: The isolation, characterization, and preclinical and clinical application of adipose-derived stem cells (ASCs) are reviewed in this article.
Abstract: The emerging field of regenerative medicine will require a reliable source of stem cells in addition to biomaterial scaffolds and cytokine growth factors. Adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate along multiple lineage pathways. The isolation, characterization, and preclinical and clinical application of adipose-derived stem cells (ASCs) are reviewed in this article.

2,189 citations


"Tendon and ligament regeneration an..." refers background in this paper

  • ...Compared to BMSCs, ASCs are (1) harvested by less invasive procedures, (2) available in greater quantities, and (3) demonstrate similar potential to differentiate along multiple mesenchymal lineages (Gimble et al., 2007)....

    [...]

Journal ArticleDOI
TL;DR: The minimum twelve-month evaluation showed excellent pain relief and improvement in the ability to perform activities of daily living despite the high rate of recurrent defects; however, at a minimum follow-up of two years, the results deteriorated with only twelve patients who had an American Shoulder and Elbow Surgeons score of >/=80.
Abstract: Background: The impact of a recurrent defect on the outcome after rotator cuff repair has been controversial. The purpose of this study was to evaluate the functional and anatomic results after arthroscopic repair of large and massive rotator cuff tears with use of ultrasound as an imaging modality to determine the postoperative integrity of the repair. Methods: Eighteen patients who had complete arthroscopic repair of a tear measuring >2 cm in the transverse dimension were evaluated at a minimum of twelve months after surgery and again at two years after surgery. The evaluation consisted of a standardized history and physical examination as well as calculation of the preoperative and postoperative shoulder scores according to the system of the American Shoulder and Elbow Surgeons. The strength of both shoulders was quantitated postoperatively with use of a portable dynamometer. Ultrasound studies were performed with use of an established and validated protocol at a minimum of twelve months after surgery. Results: Recurrent tears were seen in seventeen of the eighteen patients. Despite the absence of healing at twelve months after surgery, thirteen patients had an American Shoulder and Elbow Surgeons score of ≥90 points. Sixteen patients had an improvement in the functional outcome score, which increased from an average of 48.3 to 84.6 points. Sixteen patients had a decrease in pain, and twelve had no pain. Although eight patients had preoperative forward elevation to <95°, all eighteen regained motion above shoulder level and had an average of 152° of elevation. At the second evaluation, a minimum of twenty-four months after surgery, the average score, according to the system of the American Shoulder and Elbow Surgeons, had decreased to 79.9 points; only nine patients had a score of ≥90 points, and six patients had a score of ≤79 points. The average forward elevation decreased to 142°. Conclusions: Arthroscopic repair of large and massive rotator cuff tears led to a high percentage of recurrent defects. The minimum twelve-month evaluation showed excellent pain relief and improvement in the ability to perform activities of daily living despite the high rate of recurrent defects; however, at a minimum follow-up of two years, the results deteriorated with only twelve patients who had an American Shoulder and Elbow Surgeons score of ≥80. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.

1,871 citations


"Tendon and ligament regeneration an..." refers background in this paper

  • ...Despite advances in surgical techniques and in the understanding of shoulder pathology, chronic tears fail to heal in 20-95% of cases (Derwin et al., 2010; Galatz et al., 2004)....

    [...]

Journal ArticleDOI
TL;DR: This is the first report of a vehicle capable of delivery of multiple angiogenic factors with distinct kinetics, and these results clearly indicate the importance of multiple growth factor action in tissue regeneration and engineering.
Abstract: The development of tissues and organs is typically driven by the action of a number of growth factors. However, efforts to regenerate tissues (e.g., bone, blood vessels) typically rely on the delivery of single factors, and this may partially explain the limited clinical utility of many current approaches. One constraint on delivering appropriate combinations of factors is a lack of delivery vehicles that allow for a localized and controlled delivery of more than a single factor. We report a new polymeric system that allows for the tissue-specific delivery of two or more growth factors, with controlled dose and rate of delivery. The utility of this system was investigated in the context of therapeutic angiogenesis. We now demonstrate that dual delivery of vascular endothelial growth factor (VEGF)-165 and platelet-derived growth factor (PDGF)-BB, each with distinct kinetics, from a single, structural polymer scaffold results in the rapid formation of a mature vascular network. This is the first report of a vehicle capable of delivery of multiple angiogenic factors with distinct kinetics, and these results clearly indicate the importance of multiple growth factor action in tissue regeneration and engineering.

1,772 citations


"Tendon and ligament regeneration an..." refers background in this paper

  • ...is still in its infancy, recent advances in controlled delivery suggest the possibility of implementing these scaffolds in the near future (Richardson et al., 2001; Santo et al., 2013)....

    [...]

  • ...P A A uthor M anuscript is still in its infancy, recent advances in controlled delivery suggest the possibility of implementing these scaffolds in the near future (Richardson et al., 2001; Santo et al., 2013)....

    [...]

Journal ArticleDOI
TL;DR: Preliminary evidence from invertebrates is included which suggests that the principles for bipolar fibril assembly were established at least 500 million years ago, and how mature fibrils are assembled from early fibrILS is reviewed.
Abstract: Collagen is most abundant in animal tissues as very long fibrils with a characteristic axial periodic structure. The fibrils provide the major biomechanical scaffold for cell attachment and anchorage of macromolecules, allowing the shape and form of tissues to be defined and maintained. How the fibrils are formed from their monomeric precursors is the primary concern of this review. Collagen fibril formation is basically a self-assembly process (i.e. one which is to a large extent determined by the intrinsic properties of the collagen molecules themselves) but it is also sensitive to cell-mediated regulation, particularly in young or healing tissues. Recent attention has been focused on "early fibrils' or "fibril segments' of approximately 10 microns in length which appear to be intermediates in the formation of mature fibrils that can grow to be hundreds of micrometers in length. Data from several laboratories indicate that these early fibrils can be unipolar (with all molecules pointing in the same direction) or bipolar (in which the orientation of collagen molecules reverses at a single location along the fibril). The occurrence of such early fibrils has major implications for tissue morphogenesis and repair. In this article we review the current understanding of the origin of unipolar and bipolar fibrils, and how mature fibrils are assembled from early fibrils. We include preliminary evidence from invertebrates which suggests that the principles for bipolar fibril assembly were established at least 500 million years ago.

1,438 citations


"Tendon and ligament regeneration an..." refers background in this paper

  • ...Mature fibrillar collagens generated from this modification spontaneously self-assemble into cross-striated fibrils in an entropy-driven manner, yielding a 67 nm repeat that characterizes the axial periodicity of collagen fibrils (Kadler et al., 1996)....

    [...]

Journal ArticleDOI
TL;DR: Findings clearly indicate that, at least in an urban population, degenerative changes are common in the tendons of people who are older than thirty-five years and that these changes are associated with spontaneous rupture.
Abstract: We evaluated specimens obtained from the biopsy of spontaneously ruptured tendons in 891 patients who were treated between 1968 and 1989. The specimens, which were removed at the time of repair, included 397 Achilles tendons, 302 biceps brachii tendons, forty extensor pollicis longus tendons, eighty-two quadriceps tendons and patellar ligaments, and seventy other tendons. Age and sex-matched control specimens, from 445 tendons taken at the time of death from the cadavera of previously healthy individuals who died accidentally, also were obtained and evaluated. The histopathological analyses of the specimens included light and polarized light microscopy and scanning and transmission electron microscopy. A healthy structure was not seen in any spontaneously ruptured tendon, but two-thirds of the control tendons were structurally healthy (p less than 0.001). There were characteristic histopathological patterns in the spontaneously ruptured tendons. Most (97 per cent) of the pathological changes were degenerative; they included hypoxic degenerative tendinopathy, mucoid degeneration, tendolipomatosis, and calcifying tendinopathy, either alone or in combination. These changes were also found in 34 per cent of the control tendons, but significantly less frequently (p less than 0.001). In the other twenty-six ruptured tendons (3 per cent), the pathological change was an intratendinous foreign body, rheumatoid tendinitis, a xanthoma, a tumor, or a tumor-like lesion such as an intratendinous ganglion. The findings clearly indicate that, at least in an urban population, degenerative changes are common in the tendons of people who are older than thirty-five years and that these changes are associated with spontaneous rupture.

1,360 citations


"Tendon and ligament regeneration an..." refers background in this paper

  • ...Degenerative tendinopathy often precedes acute ruptures, with the former considered a failed healing response that is characterized by hypervascularity, mucoid degeneration, ectopic bone and cartilage nodules, and disorganized extracellular matrix (Kannus and Jozsa, 1991; Riley, 2008)....

    [...]