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Sutures are primarily used in surgery to draw tissues together. Almost all sutures only play the role of mechanically tie wound tissues together, but they do not have additional functions. For this reason, hybrid sutures with targeted mechanical properties and biological activities are of great interest (Hu & Huang, 2010). Tendons and cartilages repair remain a challenging clinical problem and a crucial medical need, as the cases involving loss of function and pain associated with tendon injuries keep increasing (Zeugolis et al., 2008). The aim of this review is to find a biomaterial that could help in the development of a new type of suture that could tie wounded tissues for their healing without any breakage nor cellular toxicity, and promoting cell growth, reducing the probabilities of a second surgical intervention.
When tears are caused in the ligaments of the body, the tendons are commonly fixed with thin fibers of inert materials like silk, polyglactin or nylon. The thinness of the suture is a stress riser, which creates shear forces and high strain levels. These are significant issues to consider when fabricating fibers to serve as sutures.
For this matter, according to Zeugolis et al. (2008), fibers made with two types of biomaterials to promote cellular growth are produced as bio-absorbable sutures for the repair of tendon tissue. Among all the different studied biomaterials, collagen has demonstrated desirable features such as high tensile strength, biodegradability, and low immunogenicity, which are favorable features for tissue engineering applications. Likewise, previous studies on extruded collagen fibers have demonstrated that such materials comprise excellent scaffolds for soft and hard tissue replacement, with similar properties to the native tissue, facilitating fibroblast migration, which occurs when fibroblasts infiltrate and remodel the collagen structure to form regenerated tissue and new tissue formation. Although momentous achievements have been made, several challenges still exist in the engineering of these scaffolds, since the ideal ones would be those that most closely mimic the naturally occurring environment in the host tissue matrix. In a study that took place in 2020, researchers Carrancá M., et al. proved that polyethylene glycol (PEG) hydrogels scaffolding properties allowed and extensive cellular infiltration and presented evidence of hydrogel degradation and neovascularization.
Furthermore, many water-soluble polymers have become an attractive field of study due to their inert properties and degradation rates. It has also been supported that collagen, which is a hydrogen donor, is able to form hydrogen bonds with the water-soluble polymers. Consequently, this polyethylene glycol (PEG), which is a low toxic and low antigenic poly-ether-diol, that has been approved by the Food and Drug Administration (FDA) for several medical applications, could be used on tissue repair. Additionally, PEG (Figure 1) has shown to facilitate cell infiltration, tissue in-growth, and an increase in the mechanical stability and enzyme degradation, with improved blood compatibility and ability to resist protein adsorption, meaning that the hydrogel is able to hold protein molecules into its surface (Zeugolis et al., 2008).
Figure 1. Images of the PEG hydrogel at room temperature. a) PEG disc 2 mm thickness and 9.1 mm in diameter, b) PEG in an inverted conical tube Carrancá M. et al. (2020).
For this reason, extruded collagen fibers (Figure 2a and 2b) with added PEG comprise a promising scaffold for tissue engineering applications. However, the engineering of these fibers has still to be improved to bring these biomaterials into clinical applications. This brings us to the analysis of a conducted research in which a novel, multi-fiber collagen-PEG fascicle structure that replicates the axial position of the natural fibers of the tendon into a fascicular arrangement was manufactured. This structure could reinforce the biomechanical capacities of the tissue to be repaired, decreasing the chances of the patient having a second tear post-surgery. The design of this biomimetic synthetic collagen fascicle (SCF) gave rise to a hypothesis statement which implied that this structure would provide the necessary behavior to cells infiltrating the scaffold. The former was based on the fascicle type of assembly and the reticulation technique used for the fiber fabrication, so that the mechanical properties of the synthetic sutures could be enhanced. By controlling scaffolding properties like strength, degradation rates, and chemical concentration amongst the PEG and collagen molecules, a SCF structure would provide an ideal microenvironment to enhance tendon regeneration. For the formation of the SCF, synthetic collagen-PEG nano-textured microfibers with reduced immunogenicity are characterized by thermal, physical, and mechanical properties like those of native tissue.
To sum up, this method allows the implementation and control of key parameters for in vivo use, such as degradation rate, cell infiltration, and nutrient diffusion, inside and outside the structure. Being able to mimic not only the native tendon composition and orientation, but also its microscopic structure, makes them suitable for our main interest: surgical repair of tendon tissue (Kew et al., 2012).
Figure 2. Typical morphology of extruded collagen fibers: (a) surface structure; (b) packed interfibrillar space; (c) schematic for the production equipment used to produce a SCF. Modified from: Synthetic collagen fascicles for the regeneration of tendon tissue. Acta biomaterialia (Kew, S. J. et al. 2012).
In addition, it is important to mention that all the materials and chemical solutions used in the experiments carried out during the research are FDA–approved, and legally distributed by pharmaceutical companies with international recognition PEG and collagen conjugates, such as the one reviewed here (Type I collagen from bovine skin) are allowed by the FDA for medical devices and regenerative medicine research (FDA Recognized Consensus Standards, 2012).
To give a background into the expense for the replication of this type of fiber fabrication procedure (Figure 2c), it would be necessary to consider that the elevated costs based on an estimated budget must be given to the high investment in specialized infrastructure. For that matter, it would be advisable to replicate the fiber manufacturing process in facilities where all the equipment required to achieve satisfactory results are available. If the previous option is not viable, then economic and infrastructure support from research centers like Tigenix Ltd., which is a European cell therapy company, and the Orthopaedic Research Unit from de University of Cambridge, which were the research centers responsible of sponsoring the development of the manufacturing process of the fibers conducted during the research and carried out by Zeugolis et al. (2008).
The novel techniques that have been developed in recent years give guidelines to future clinical implementations, offering improvements on tendon repair surgeries to give the patient a better recovery by shortening the healing times for the patients. That is to say, since there is a huge number of patients going for a second intervention, that the application of new biocompatible sutures would decrease the possibilities of the patient suffering from a second tendon tear, helping the health sector to deal with this huge burden.
References
Carrancá M, Griveau L, Remoué N, et al. Versatile lysine dendrigrafts and polyethylene glycol hydrogels with inherent biological properties: in vitro cell behavior modulation and in vivo biocompatibility. J Biomed Mater Res. 2020;1–12. https://doi.org/10.1002/jbm.a.37083
Hu, W. and Huang, Z.‐M. (2010), Biocompatibility of braided poly(L‐lactic acid) nanofiber wires applied as tissue sutures. Polym. Int., 59: 92-99. https://doi-org.udlap.idm.oclc.org/10.1002/pi.2695
Kew, S. J., Gwynne, J. H., Enea, D., Brookes, R., Rushton, N., Best, S. M., & Cameron, R. E. (2012). Synthetic collagen fascicles for the regeneration of tendon tissue. Acta biomaterialia, 8(10), 3723-3731.
Recognized Consensus Standards. (2012). Fda.gov. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/detail.cfm?standard__identification_no=30083
Zeugolis, D. I., Paul, R. G., & Attenburrow, G. (2008). Extruded collagen‐polyethylene glycol fibers for tissue engineering applications. Journal of Biomedical Materials Research Part B: Applied Biomaterials: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 85(2), 343-352.
About the authors
Aranza Rodríguez Cruz.
Student of the sixth semester of the degree in Biomedical Engineering. She belongs to the SOMIB UDLAP Student Chapter, which is the student representation of the Mexican Society of Biomedical Engineering at the UDLAP and is president of the IEEE UDLAP Student Branch where she is also an active member in the affinity groups of Women in Engineering (WIE) and Special Interest Group in Humanitarian Technologies (SIGHT). She is also a member of a Rotaract Club belonging to Rotary International.
aranza.rodriguezcz@udlap.mx
Sofía García Peña.
Sixth semester student of the Biomedical Engineering degree. She is a member of the Honors Program with the research project related to the study of the spatio-temporal distribution of electroencephalography signals during rest, imagination, and motor performance. In addition, she belongs to the IEEE-UDLAP Student Branch as a student member and as an active member in the affinity groups Women in Engineering (WIE) and Special Interest Group in Humanitarian Technologies (SIGHT) of the IEEE. She belongs to the SOMIB UDLAP Student Chapter, which is a student representation of the Mexican Society of Biomedical Engineering.
Last modified: 11 mayo, 2021