Tendon-Inspired Nanotopographic Scaffold for Tissue Regeneration in Rotator Cuff Injuries.
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ABSTRACT:
SUBMITTER: Kim W
PROVIDER: S-EPMC7301599 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Tendon-Inspired Nanotopographic Scaffold for Tissue Regeneration in Rotator Cuff Injuries.
Kim Woochan W Kim Ga-Eon GE Attia Abdou Mohamed M Kim Sujin S Kim Daun D Park Sunho S Kim Yang-Kyung YK Gwon Yonghyun Y Jeong Sung-Eun SE Kim Myung-Sun MS Kim Jangho J
ACS omega 20200602 23
Acute and chronic rotator cuff (RC) tears are common etiologies of shoulder disabilities. Despite the advanced surgical techniques and graft materials available for tendon repair, the high re-tear rate remains a critical challenge in RC healing. Inspired by the highly organized nanotopography of the extracellular matrix (ECM) in tendon tissue of the shoulder, nanotopographic scaffolds are developed using polycaprolactone for the repair and regeneration of RC tendons. The scaffolds show appropria ...[more]
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Project description:Repairing massive rotator cuff tendon defects remains a challenge due to the high retear rate after surgical intervention. 3D printing has emerged as a promising technique that enables the fabrication of engineered tissues with heterogeneous structures and mechanical properties, as well as controllable microenvironments for tendon regeneration. In this study, we developed a new strategy for rotator cuff tendon repair by combining a 3D printed scaffold of polylactic-co-glycolic acid (PLGA) with cell-laden collagen-fibrin hydrogels. We designed and fabricated two types of scaffolds: one featuring a separate layer-by-layer structure and another with a tri-layered structure as a whole. Uniaxial tensile tests showed that both types of scaffolds had improved mechanical properties compared to single-layered PLGA scaffolds. The printed scaffold with collagen-fibrin hydrogels effectively supported the growth, proliferation, and tenogenic differentiation of human adipose-derived mesenchymal stem cells. Subcutaneous implantation of the multilayered scaffolds demonstrated their excellent in vivo biocompatibility. This study demonstrates the feasibility of 3D printing multilayered scaffolds for application in rotator cuff tendon regeneration.
| S-EPMC7212184 | biostudies-literature
Project description:Background Rotator cuff tears are a common source of shoulder pain and dysfunction. An irreparable rotator cuff tear poses a particular treatment challenge. There have been few studies reporting the outcomes of lower trapezius tendon (LTT) transfer for irreparable rotator cuff injuries. Therefore, the purpose of this review is to summarize the postoperative functional outcomes and complications of patients undergoing a LTT transfer for massive irreparable rotator cuff injuries. Methods A scoping review was performed using the Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases with the search terms “trapezius” AND “transfer.” Of 362 studies included for initial screening, 37 full-text citations were reviewed, with 5 studies meeting all the inclusion criteria to be included in the review. Two reviewers extracted data on study design, patient demographics, surgical technique, functional outcomes, range of motion (ROM), and complications for each study according to the predefined criteria. Results Improvements in the preoperative to postoperative functional status, identified using the Disabilities of the Arm, Shoulder, and Hand (50.34 to 18), The American Shoulder and Elbow Surgeons Score (48.56 to 80.24), Visual Analog Scale (5.8 to 1.89), Single Assessment Numeric Evaluation (34.22 to 69.86), and Subjective Shoulder Value (52.24 to 77.66), were evident across all 5 studies. Preoperative to postoperative increases in ROM were seen for flexion (85 to 135), external rotation (18 to 52), and abduction (50 to 98). The overall complication rate was 18%, with seroma formation (8%) as the most common postoperative complication. Discussion/Conclusion Our analysis showed that LTT transfer improved postoperative function, ROM, and pain for patients with irreparable rotator cuff tears with an overall complication rate of 18%. Future controlled studies are required to directly compare LTT transfer to other tendon transfers and other surgical techniques for irreparable rotator cuff tears.
| S-EPMC10426520 | biostudies-literature
Project description:BACKGROUND:Scaffolds have considerably advanced in recent years. In orthopaedic surgery, scaffolds have been used as grafts in procedures involving tendon and ligament reconstruction. This paper aimed to produce and evaluate decellularized tendon scaffolds (DTSs) from biomechanical, microscopic, macroscopic and in vivo perspectives. METHODS:Bilateral gastrocnemius muscle tendons from 18 adult New Zealand rabbits were collected. Of these 36 tendons, 11 were used as controls (Group A - control), and 25 were used in the decellularization protocol (Group B - DTS). The groups were subjected to histological, biomechanical and macroscopic analyses, and Group B - DTS was subjected to an additional in vivo evaluation. In the decellularization protocol, we used a combination of aprotinin, ethylenediamine tetraacetic acid (EDTA), sodium dodecyl sulfate (SDS) and t-octyl-phenoxypolyethoxyethanol (Triton X-100) for six days. During this period, the scaffolds were kept at room temperature on an orbital shaker with constant motion. RESULTS:The DTSs showed an increased cross-sectional area and inter-fascicular distance and no change in parallelism or matrix organization. The nuclear material was not organized in the DTSs as it was in the control. In the biomechanical analysis, no significant differences were found between the groups after analysing the ultimate tensile load, stiffness, and elongation at the ultimate tensile load. During the in vivo evaluation, mononuclear cell infiltration was noted. CONCLUSIONS:The evaluated decellularization protocol generated a tendon scaffold, maintained the most important biomechanical characteristics and permitted cell infiltration.
| S-EPMC7568836 | biostudies-literature
Project description:The rotator cuff consists of several tendons and muscles that provide stability and force transmission in the shoulder joint. Whereas most rotator cuff tears are amenable to suture repair, the overall success rate of repair is low, and massive tears are prone to re-tear. Extracellular matrix (ECM) patches are used to augment suture repair, but they have limitations. Tissue-engineered approaches provide a promising solution for massive rotator cuff tears. Previous studies have shown that, compared to nonaligned scaffolds, aligned electrospun polymer scaffolds exhibit greater anisotropy and exert a greater tenogenic effect. Nevertheless, achieving rapid cell infiltration through the full thickness of the scaffold is challenging, and scaling to a translationally relevant size may be difficult. Our goal was to evaluate whether a novel method of alignment, combining a multilayered electrospinning technique with a hybrid of several electrospinning alignment techniques, would permit cell infiltration and collagen deposition through the thickness of poly(ε-caprolactone) scaffolds following seeding with human adipose-derived stem cells. Furthermore, we evaluated whether multilayered aligned scaffolds enhanced collagen alignment, tendon-related gene expression, and mechanical properties compared to multilayered nonaligned scaffolds. Both aligned and nonaligned multilayered scaffolds demonstrated cell infiltration and ECM deposition through the full thickness of the scaffold after only 28days of culture. Aligned scaffolds displayed significantly increased expression of tenomodulin compared to nonaligned scaffolds and exhibited aligned collagen fibrils throughout the full thickness, the presence of which may account for the increased yield stress and Young's modulus of cell-seeded aligned scaffolds along the axis of fiber alignment.Statement of significanceRotator cuff tears are an important clinical problem in the shoulder, with over 300,000 surgical repairs performed annually. Re-tear rates may be high, and current methods used to augment surgical repair have limited evidence to support their clinical use due to inadequate initial mechanical properties and slow cellular infiltration. Tissue engineering approaches such as electrospinning have shown similar challenges in previous studies. In this study, a novel technique to align electrospun fibers while using a multilayered approach demonstrated increased mechanical properties and development of aligned collagen through the full thickness of the scaffolds compared to nonaligned multilayered scaffolds, and both types of scaffolds demonstrated rapid cell infiltration through the full thickness of the scaffold.
| S-EPMC4560626 | biostudies-literature
Project description:The risk of the development of tendon disorders or ruptures increases with age, but it is unclear whether intrinsic fitness during lifetime might also affect tendon properties. To investigate this, a contrasting rat model of high-capacity runners (HCR with high intrinsic fitness) and low-capacity runners (LCR with low intrinsic fitness) was employed. Histological and molecular changes in rotator cuff (RC) tendons from 10 weeks old (young; HCR-10 and LCR-10) and 100 weeks old (old; HCR-100 and LCR-100) female rats were investigated. Age-dependent changes of RC tendons observed in HCR and LCR were increase of weight, decrease of tenocytes and RNA content, reduction of the wavy pattern of collagen and elastic fibers, repressed expression of Col1a1, Eln, Postn, Tnmd, Tgfb3 and Egr1 and reduction of the Col1:Col3 and Col1:Eln ratio. The LCR rats showed less physical activity, increased body weight, signs of metabolic disease and a reduced life expectancy. Their RC tendons revealed increased weight (more than age-dependent) and enlargement of the tenocyte nuclei (consistent with degenerative tendons). Low intrinsic fitness led to repressed expression of a further nine genes (Col3a1, Fbn1, Dcn, Tnc, Scx, Mkx, Bmp1, Tgfb1, Esr1) as well as the rise of the Col1:Col3 and Col1:Eln ratios (related to the lesser expression of Col3a1 and Eln). The intrinsic fitness influences the female RC tendons at least as much as age. Lower intrinsic fitness accelerates aging of RC tendons and leads to further impairment; this could result in decreased healing potential and elasticity and increased stiffness.
| S-EPMC8962357 | biostudies-literature
Project description:Despite advancements in surgical techniques and materials for rotator cuff repair procedures, primary repair failures remain common. This study examines the use of electrochemically aligned collagen (ELAC) threads woven into biotextile scaffolds as grafts to repair critical infraspinatus tendon defects in New Zealand White rabbits. Three surgical treatment groups were evaluated: rabbits undergoing direct repair as operative controls, rabbits receiving ELAC scaffolds alone, and rabbits treated with mesenchymal stem cell (MSC)-seeded ELAC scaffolds. In each animal, the intact, contralateral infraspinatus served as an internal positive control. Tendon-bone constructs were harvested after 3 months in vivo and outcome measures included biomechanical testing, histological staining, and immunohistochemical staining. Biomechanical testing revealed that maximum load-bearing capacity was comparable between all groups, while MSC-seeded scaffold repairs exhibited increased stiffness relative to non-seeded scaffold repairs. Histological staining revealed robust collagen deposition around ELAC fibers and increased cellularity within the continuum of woven scaffolds as compared to native tendon. Immunohistochemical staining revealed presence of collagens I and III in all groups, but procollagen I and the tendon-specific marker tenomodulin were only observed in seeded and non-seeded ELAC scaffold repairs. Findings of this pilot study warrant continued investigation of ELAC biotextile scaffolds for repair of critically-sized rotator cuff tendon defects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1864-1876, 2019.
| S-EPMC7369170 | biostudies-literature
Project description:A histologically normal insertion site does not regenerate following rotator cuff tendon-to-bone repair, which is likely due to abnormal or insufficient gene expression and/or cell differentiation at the repair site. Techniques to manipulate the biologic events following tendon repair may improve healing. We used a sheep infraspinatus repair model to evaluate the effect of osteoinductive growth factors and BMP-12 on tendon-to-bone healing. Magnetic resonance imaging and histology showed increased formation of new bone and fibrocartilage at the healing tendon attachment site in the treated animals, and biomechanical testing showed improved load-to-failure. Other techniques with potential to augment repair site biology include use of platelets isolated from autologous blood to deliver growth factors to a tendon repair site. Modalities that improve local vascularity, such as pulsed ultrasound, have the potential to augment rotator cuff healing. Important information about the biology of tendon healing can also be gained from studies of substances that inhibit healing, such as nicotine and antiinflammatory medications. Future approaches may include the use of stem cells and transcription factors to induce formation of the native tendon-bone insertion site after rotator cuff repair surgery.
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Project description:Various biomaterial technologies are promising for tissue engineering, including electrospinning, but commercial scale-up of throughput is difficult. The goal of the study was to evaluate meltblown fabrics as candidate scaffolds for rotator cuff tendon tissue engineering. Meltblown poly(lactic acid) fabrics were produced with several polymer crystallinities and airflow velocities [500(low), 900(medium) or 1400(high) m3air/h/m fabric]. Fiber diameter, alignment, and baseline bidirectional tensile mechanical properties were evaluated. Attachment and spreading of human adipose-derived stem cells (hASCs) were evaluated over 3 days immediately following seeding. After initial screening, the fabric with the greatest Young's modulus and yield stress was selected for 28-day in vitro culture and for evaluation of tendon-like extracellular matrix production and development of mechanical properties. As expected, airflow velocity of the polymer during meltblowing demonstrated an inverse relationship with fiber diameter. All fabrics exhibited fiber alignment parallel to the direction of collector rotation. All fabrics demonstrated mechanical anisotropy at baseline. Cells attached, proliferated, and spread on all fabrics over the initial three-day culture period. Consistent with the observed loss of integrity of the unseeded biomaterial, hASC-seeded scaffolds demonstrated a significant decrease in Young's modulus over 28 days of culture. However, dsDNA, sulfated glycosaminoglycan, and collagen content increased significantly over 28 days. Histology and polarized light microscopy demonstrated collagen deposition and alignment throughout the thickness of the scaffolds. While fiber diameters approximated an order of magnitude greater than those previously reported for electrospun scaffolds intended for tendon tissue engineering, they were still within the range of collagen fiber diameters found in healthy tendon. The extent of matrix production and alignment was similar to that previously observed for multilayered electrospun scaffolds. While the Young's modulus of scaffolds after 28 days of culture was lower than native rotator cuff tendon, it approximated that reported previously following culture of electrospun scaffolds and was on the same order of magnitude as of current Food and Drug Administration-approved patches for rotator cuff augmentation. Together, these data suggest that with minor polymer and parameter modifications, meltblown scaffolds could provide an economical, high-throughput production alternative method to electrospinning for use in rotator cuff tendon tissue engineering.
| S-EPMC5610401 | biostudies-literature
Project description:BackgroundRotator Cuff (RC) tendon tearing is a common clinical problem and there is a high incidence of revision surgery due to re-tearing. In an effort to improve patient outcome and reduce surgical revision, scaffolds have been widely used for augmentation of RC repairs. However, little is known about how scaffolds support tendon stem cell growth or facilitate tendon regeneration. The purpose of this study is to evaluate the structural and biological properties of a bioactive collagen scaffold (BCS) with the potential to promote tendon repair. Additionally, we conducted a pilot clinical study to assess the safety and feasibility of using the BCS for repair of RC tears.MethodsA series of physical, ultrastructural, molecular and in vitro tests determined the biocompatibility and teno-inductive properties of this BCS. In addition, a prospective case study of 18 patients with RC tendon tears (>20 mm in diameter) was performed in an open-label, single-arm study, involving either mini-open or arthroscopic surgical RC repair with the BCS. Clinical assessment of RC repair status was undertaken by MRI-imaging at baseline, 6 and 12 months and patient evaluated questionnaires were taken at baseline as well as 3, 6 & 12 months.ResultsThe BCS consists of highly purified type-I collagen, in bundles of varying diameter, arranged in a higher order tri-laminar structure. BCS have minimal immunogenicity, being cell and essentially DNA-free as well as uniformly negative for the porcine α-Gal protein. BCS seeded with human primary tendon-derived cells and exposed to 6% uniaxial loading conditions in vitro, supported increased levels of growth and proliferation as well as up-regulating expression of tenocyte differentiation marker genes including TNMD, Ten-C, Mohawk and Collagen-1α1. To test the safety and feasibility of using the BCS for augmentation of RC repairs, we followed the IDEAL framework and conducted a first, open-label single arm prospective case series study of 18 patients. One patient was withdrawn from the study at 3 months due to wound infection unrelated to the BCS. The remaining 17 cases showed that the BCS is safe to be implanted. The patients reported encouraging improvements in functional outcomes (ASES, OSS and Constant-Murley scores), as well as quality of life assessments (AQoL) and a reduction in VAS pain scores. MRI assessment at 12 months revealed complete healing in 64.8% patients (11/17), 3 partial thickness re-tears (17.6%) and 3 full thickness re-tears (17.6%).ConclusionThe BCS is composed of type-I collagen that is free of immunogenic proteins and supports tendon-derived cell growth under mechanical loading in vitro. This pilot study shows that it is safe and feasible to use BCS for RC argumentation and further controlled prospective studies are required to demonstrate its efficacy.The translational potential of this articleThe results of this study indicate that this bioactive collagen scaffold has unique properties for supporting tendon growth and that it is non-immunogenic. The clinical study further confirms that the scaffold is a promising biological device for augment of human rotator cuff repairs.
| S-EPMC8671806 | biostudies-literature
Project description:Rotator cuff tears are common musculoskeletal injuries that can cause significant pain and disability. While the clinical results of rotator cuff repair can be good, failure of tendon healing remains a significant problem. Molecular mechanisms underlying structural failure following surgical repair remain unclear. Histologically, enhanced inflammation, disorganization of the collagen fibers, calcification, apoptosis and tissue necrosis affect the normal healing process. Mesenchymal stem cells (MSCs) have the ability to provide improved healing following rotator cuff repair via the release of mediators from secreted 30-100 nm extracellular vesicles called exosomes. They carry regulatory proteins, mRNA and miRNA and have the ability to increase collagen synthesis and angiogenesis through increased expression of mRNA and release of proangiogenic factors and regulatory proteins that play a major role in proper tissue remodeling and preventing extracellular matrix degradation. Various studies have shown the effect of exosomes on improving outcome of cutaneous wound healing, scar tissue formation, degenerative bone disease and Duchenne Muscular Dystrophy. In this article, we critically reviewed the potential role of exosomes in tendon regeneration and propose the novel use of exosomes alone or seeded onto biomaterial matrices to stimulate secretion of favorable cellular factors in accelerating the healing response following rotator cuff repair.
| S-EPMC6830879 | biostudies-literature