Biomaterials as Tendon and Ligament Substitutes: Current Developments

Tendon and ligament have specialized dynamic microenvironment characterized by a complex hierarchical extracellular matrix essential for tissue functionality, and responsible to be an instructive niche for resident cells. Among musculoskeletal diseases, tendon/ligament injuries often result in pain, substantial tissue morbidity, and disability, affecting athletes, active working people and elder population. This represents not only a major healthcare problem but it implies considerable social and economic hurdles. Current treatments are based on the replacement and/or augmentation of the damaged tissue with severe associated limitations. Thus, it is evident the clinical challenge and emergent need to recreate native tissue features and regenerate damaged tissues. In this context, the design and development of anisotropic bioengineered systems with potential to recapitulate the hierarchical architecture and organization of tendons and ligaments from nano to macro scale will be discussed in this chapter. Special attention will be given to the state-of-the-art fabrication techniques, namely spinning and electrochemical alignment techniques to address the demanding requirements for tendon substitutes, particularly concerning the importance of biomechanical and structural cues of these tissues. Moreover, the poor innate regeneration ability related to the low cellularity and vascularization of tendons and ligaments also anticipates the importance of cell based strategies, particularly on the stem cells role for the success of tissue engineered therapies. In summary, this chapter provides a general overview on tendon and ligaments physiology and current conventional treatments for injuries caused by trauma and/or disease. Moreover, this chapter presents tissue engineering approaches as an alternative to overcome the limitations of current therapies, focusing on the discussion about scaffolds design for tissue substitutes to meet the regenerative medicine challenges towards the functional restoration of damaged or degenerated tendon and ligament tissues.Portuguese Foundation for Science and Technology for the post-doctoral grant (SFRH/BPD/111729/2015) and for the projects Recognize (UTAP-ICDT/CTM-BIO/0023/2014) and POC I-01-0145-FEDER-007

Biodegradable polymeric fiber structures in tissue engineering

Tissue engineering offers a promising new approach to create biological alternatives to repair or restore function of damaged or diseased tissues. To obtain three-dimensional tissue constructs, stem or progenitor cells must be combined with a highly porous three-dimensional scaffold, but many of the structures purposed for tissue engineering cannot meet all the criteria required by an adequate scaffold because of lack of mechanical strength and interconnectivity, as well as poor surface characteristics. Fiber-based structures represent a wide range of morphological and geometric possibilities that can be tailored for each specific tissue-engineering application. The present article overviews the research data on tissue-engineering therapies based on the use of biodegradable fiber architectures as a scaffold

Engineering tendon and ligament tissues : present developments towards successful clinical products

Musculoskeletal diseases are one of the leading causes of disability worldwide. Among them, tendon and ligament injuries represent an important aspect to consider in both athletes and active working people. Tendon and ligament damage is an important cause of joint instability, and progresses into early onset of osteoarthritis, pain, disability and eventually the need for joint replacement surgery. The social and economical burden associated with these medical conditions presents a compelling argument for greater understanding and expanding research on this issue. The particular physiology of tendons and ligaments (avascular, hypocellular and overall structural mechanical features) makes it difficult for currently available treatments to reach a complete and long-term functional repair of the damaged tissue, especially when complete tear occurs. Despite the effort, the treatmentmodalities for tendon and ligament are suboptimal, which have led to the development of alternative therapies, such as the delivery of growth factors, development of engineered scaffolds or the application of stem cells, which have been approached in this review

Fabrication and Characterization of a Silk-PCL Based Scaffold for Ligament Graft

Ligament gets damaged very often in cutting and pivoting sports. Current gold standards for ligament replacement are based on autografts which has limitations of inadequate strength and donor site morbidity. Thus, ligament tissue engineering is promising strategy for replacing severely damaged ligaments beyond repair. The objective of current study is to fabricate a hybrid scaffold for ligament graft with high tensile strength which will support cell proliferation. Briefly, knitted silk scaffold was made by use of wild type silk from Antheraea mylitta. Polycaprolactone (PCL) was electrospun on these knitted scaffold to facilitate cell growth. Degradation study and mechanical testing of scaffolds were carried out at five time points (0, 3, 7, 14, 21 d). Mouse fibroblasts (L929) were cultured on these nano-micro scaffolds to investigate the cell adhesion and proliferation potential. Cell proliferation was visualized under fluorescent microscopy and was analysed by MTT assay. Hybrid scaffolds showed slow degradation rate and high tensile strength, 22.75 ± 0.43 N at end of day 21. Cell adhesion efficiency was determined to be 92.28±0.61%. L929 cells grew profusely on the hybrid scaffold as confirmed from fluorescent microscopy and MTT assay. Silk-PCL based hybrid scaffold promises to be a better platform for ligament tissue engineering with optimal biocompatibility and mechanical properties

Fabrication of silk-based composite scaffold for bone-ligament-bone graft using aqueous polymeric dispersion technique

Tissue engineering is a promising technology for treating tissue defects or replacing nonfunctional tissues/organs. It relies upon a temporary scaffold that is basically an artificial structure which provides the support for 3D tissue formation or organogenesis. Ideally, scaffolds should be able to accommodate human cells, orchestrate their growth and differentiation leading to tissue regeneration and ultimately make it feasible for implantation. Major sports injuries involve the damage of cartilages, ligaments, tendons and the enthesis. Since ligament injury is most common and ligament-alone grafts are not so successful to replace the injured ligaments, the researchers are experimenting with the construction of a composite scaffold which can guide the stem cells to differentiate into fibrocartilage that bridges of Bone-Ligament interface i.e. enthesis. In the current project, a composite silk-based scaffold was fabricated by incorporating multiple compartments for B-L-B graft. The core scaffold was prepared by knitting the silk fibers (from Bombyx mori) to provide required mechanical strength. The individual compartments over the knitted scaffold were coated with specific biocompatible components (i.e. hydroxyapatite for bone, Polyethylene oxide and & Polyethylene glycol for ligament and cartilage) blended with gelatin using Aqueous Polymer Dispersion (APD) Technique. The morphology of fabricated scaffolds was studied under optical microscope and SEM (Scanning Electron Microscope) while the mechanical properties were analysed through the Texture Analyzer. The particle sizes were found to be between 10-1000 nm. It was concluded that silk based multi-compartmental scaffolds fabricated from APD technique are suitable for enthesis tissue engineering due to their porosity and matching mechanical properties. However, the scaffolds need to be confirmed for their bioactivity by culturing live cells on respective compartment

In-vitro Study of Cartilage Differentiation for Enthesis Tissue Engineering

Ligaments are a dense connective tissue responsible for joint movements and stability. Anterior Cruciate Ligament (ACL) is one of the four major ligaments of the knee. Being subjected to high physiological loads, ACL is commonly injured,Surgical management with ligament grafts is often required, but these treatments are associated with complications of reduced strength, joint stiffness, repair-rupture. Interface Tissue engineering (ITE) may effectively address these complications where an artificial ligament incorporating the interfacial fibrocartilage can be engineered to provide similar mechanical and functional characteristics as the native tissue. Therefore a multi-compartmental scaffold that can induce the growth and differentiation of fibrocartilage at the interface of engineered bone and ligament tissues would mimic the native structure of bone-ligament –bone block with deposition of appropriate extracellular matrix (ECM) in respective compartments and possession of adequate mechanical properties to support the healing tissue. The current project has focused on the fabrication of a silk-based knitted scaffold which comprises of three compartments, one each for the bone, ligament and enthesis tissues. an array of methods were adopted for surface modification of the compartmentalized knitted silk scaffold by using bio-polymers such as silk solution, chitosan, gelatin and hydroxyapatite on the appropriate compartments. The ligament and bone compartments were reserved for mature cell line culture like MG63 and Saos-2. The various methods used for coatings of polymers over the knitted-silk were alternate soaking, plain coating and freeze-drying. The knitted scaffold was characterized for its water absorption biodegradability,tensile strength, and bio compatibility. Such a complex graft with incorporation of enthesis in laboratory can provide natural insertional strength at the interface and can change the current scenario of replacing injured ligaments

Structural Design, Fabrication and Evaluation of Resorbable Fiber-Based Tissue Engineering Scaffolds

The use of tissue engineering to regenerate viable tissue relies on selecting the appropriate cell line, developing a resorbable scaffold and optimizing the culture conditions including the use of biomolecular cues and sometimes mechanical stimulation. This review of the literature focuses on the required scaffold properties, including the polymer material, the structural design, the total porosity, pore size distribution, mechanical performance, physical integrity in multiphase structures as well as surface morphology, rate of resorption and biocompatibility. The chapter will explain the unique advantages of using textile technologies for tissue engineering scaffold fabrication, and will delineate the differences in design, fabrication and performance of woven, warp and weft knitted, braided, nonwoven and electrospun scaffolds. In addition, it will explain how different types of tissues can be regenerated by each textile technology for a particular clinical application. The use of different synthetic and natural resorbable polymer fibers will be discussed, as well as the need for specialized finishing techniques such as heat setting, cross linking, coating and impregnation, depending on the tissue engineering application

The Essex-Lopresti lesion

International audienc