|
 
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| REVIEW ARTICLE |
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| Year : 2017 | Volume
: 2
| Issue : 4 | Page : 85-102 |
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Biomaterials and surgical applications: The translational perspective
Brenda Vega-Ruiz, Rodrigo Ramos-Zúñiga, Ivan Segura Duran, Yara Ursiel-Ortega
Department of Neurosciences, University Center of Health Sciences, Translational Neurosciences Institute, University of Guadalajara, Guadalajara, Jalisco, Mexico
| Date of Submission | 05-Jul-2017 |
| Date of Acceptance | 16-Oct-2017 |
| Date of Web Publication | 28-Dec-2017 |
Correspondence Address:
Rodrigo Ramos-Zúñiga
Department of Neurosciences, University Center of Health Sciences, Translational Neurosciences Institute, University of Guadalajara, 44340 Guadalajara, Jalisco
Mexico
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ts.ts_17_17
Basic research provides the results necessary to pursue translational work, where basic and translational approaches used in conjunction can allow for an increased impact in solving public health problems. Biomaterials draws from both approaches and are used today in many surgical specialty areas, such as tissue regeneration and regenerative medicine. These materials can be used as replacements for tissue, as scaffolds for regeneration, as substrates for cell growth, as drug-releasing or bioactive molecule-releasing vehicles, and as several other medical devices. Biopolymers used in regenerative medicine provide a good example of such materials and demonstrate the methodology of a translational approach, where the product begins at the laboratory bench, is applied in preclinical stages, and is finally delivered as a new medical solution back to the patient. The biocompatible, biodegradable, and bioactive properties of some of these polymers have opened different possibilities for their use in the repair and/or regeneration of different tissues, including skin, bone, cartilage, nerves, liver, and muscle. This article serves as a review of the properties of these biopolymers, their use in tissue engineering, and promising alternatives in regenerative medicine. Keywords: Biomaterials, chitosan scaffold, tissue engineering, translational medicine
How to cite this article:
Vega-Ruiz B, Ramos-Zúñiga R, Duran IS, Ursiel-Ortega Y. Biomaterials and surgical applications: The translational perspective. Transl Surg 2017;2:85-102 |
How to cite this URL:
Vega-Ruiz B, Ramos-Zúñiga R, Duran IS, Ursiel-Ortega Y. Biomaterials and surgical applications: The translational perspective. Transl Surg [serial online] 2017 [cited 2018 Jun 22];2:85-102. Available from: http://www.translsurg.com/text.asp?2017/2/4/85/221876 |
| Introduction | |  |
Regenerative medicine creates strategies to promote repair of damaged tissues, and the popularity of this research area and its treatment potential toward a great deal of pathological conditions make it attractive for a translational approach. Through translation, outcomes will be more timely, precise, and available for patients in medical situations where chronic and degenerative processes are found or when there are lesions or trauma that morphologically and functionally affect a given tissue and/or organ.[1],[2],[3],[4] In such circumstances, the biomaterial can be found not only as a bioimplant with an anatomical impact but also as a substitute for a regenerative process.[5],[6],[7] In the search for new alternatives to treat several diseases, tissue engineering uses biomaterials and applies them in a timely and efficient manner. This review attempts to create a complete picture about the alternatives present in the use of biomaterials and translational medicine.[8]
| The Principle of Regenerative Medicine | | |
The current use of biomaterials is vastly different from only 10 years ago. Implantable medical devices are still important, and medical technologies contribute to a broad range of uses for these materials, such as serving as vehicles for delivery of drugs and genes, scaffolds for tissue engineering and cell therapies, three-dimensional (3D) organ printing, image-based nanotechnology, diagnostic systems, and microelectronic devices.[9],[10],[11],[12],[13],[14]
These new technologies include not only materials such as metals, ceramics, and synthetic polymers, but also biopolymers, self-assembled nanoparticles, carbon nanotubes, and quantic points. These technologies set an expectation for innovation that creates a constant process of design change and improvement. Among these innovations, some are driven by how polymer biomaterials have characteristics of biocompatibility, low cost, and wide use in a variety of representative scaffolds and biological systems. Several materials have been designed to create scaffolds that function similar to biological systems with the purpose of being directly controlled by tissue interactions and components.[15],[16],[17],[18] These materials can be associated with bioactive compounds such as tissue, cells, organs, and even viruses. Furthermore, recent technological advances have given way to growth and progress in the field of stem cell biology. Biomaterials can be used also for tissue regeneration and for the development and improvement of 3D cultures used in scaffolds. The focus for the creation of biomaterials in the field of biomedicine must be interdisciplinary, based on the combination of new generation technologies and cell-based therapies that can lead to progress in tissue regeneration for the future.[19],[20],[21],[22] The bioactive component in tissue engineering must be incorporated into the study of the design, regenerative capacity, biocompatibility, and characteristics of the biopolymer chosen. The selection of polymers and design of tissue types are broad and are being fully investigated within the context of translational research.
“Regenerative engineering” is meant to create systems to repair large and complex tissues that incorporate advances in the fields of biomaterials, stem cell technology, and biology. We consider that the latest innovations in the science of materials and nanotechnology will allow for the redesigning of native tissues. The newly designed polymers incorporate bioactivity and physical features of the host tissue, mantaining also a role to induce regeneration. In general terms, materials used as scaffolds in tissue engineering offer a platform meant to hold an orderly proliferative and regenerative process that is well organized according to the characteristics required by the recipient tissue, where design is based on the primary biological conditions.[23],[24],[26] Damage to musculoskeletal tissue is an example where there is extremely limited endogenous regenerative capacity; however, with the use of bioactive scaffolds, this process becomes more dynamic and gives the possibility of functional regeneration. One of the challenges for successful application of biomaterials is to reduce the immune response that arises when intervening in a biological system.[27],[28],[29],[30]
Tissue engineering is an important treatment strategy that will be used in regenerative medicine ever more frequently. Research on functional biomaterials focuses on the creation and improvement of scaffolds, which may be used to repair or regenerate an organ or tissue. Scaffolding is one of the basic strategies for tissue engineering. The development of biomaterials made from natural polymers has become common and popular. An example is chitosan, a copolymer derived from alkaline deacetylation of chitin. Expectations from the use of these scaffolds in new biomedical applications are increasing as more knowledge is learned about their biological, chemical, and mechanical properties.[1],[2],[3],[4] Due to their multiple and varied biological properties (biocompatibility, biodegradability, and bioactivity), an important increase has occurred in their use in tissue engineering for repair and/or regeneration of different tissues, including skin, bone, cartilage, nerves, liver, muscle, as well as their use in wound healing, drug-release vehicles, cell growth substrates, and scaffolds. [31],[32],[33],[34],[35]
The current strategies of regenerative medicine focus on the reestablishment of functional and morphological architecture of pathologically altered tissues.[36],[37],[38],[39],[40] In the last few years, biologically active scaffolds have been devised on the basis of extracellular matrix analogs that have induced tissue and organ growth. To restore function or to regenerate tissue, a scaffold is needed to act as a matrix for cell proliferation and extracellular matrix deposit, with subsequent growth until tissues are totally restored or to regenerated. The translational approach is appropriate in regenerative medicine, where the main goal is to combine existing and new technologies to devise, for example biomaterial scaffolds with controlled porous structures, which can be applied in the regeneration of damaged or injured tissues/organs. The design of these strategies should be made so that they can be immediately available for patients in clinical settings.[41],[42],[43],[44],[45],[46],[47]
| Applications of Biomaterials in Biomedicine and Their Translational Impact | | |
There are multiple strategies to apply biomaterials for reconstruction of tissues, either for functional or for cosmetic purposes. The focus for creating a biomaterial depends on the type of tissue to be replaced and its functions within a biological system. An important case is the treatment of bone defects, in reconstructive surgery. It is known that a perfect scaffold in bone tissue engineering must have the following features: (1) biocompatibility, (2) be osteoconductive and osteoinductive, (3) the biodegradation rate must be similar to the natural bone production, (4) the porous structure must provide an appropriate matrix for proliferation and cell differentiation, (5) mechanical properties must be similar to those in bone, and (6) a proper structure to allow vascularization.[48] [Table 1] shows the different strategies that have been used and their applications in biomedicine focused on bone tissue.
The existing clinical approaches to repair nervous tissue injuries include end-to-end suture, fascicular suture, nerve graft (autologous or allogeneic), and nerve bridging. Different biogenic matrices have been used to create a favorable environment for nerve regeneration, given the limited capacity to regenerate in long-and-severe lesions or defects.[73] [Table 2] describes the different strategies that have been used and their applications in nervous tissue biomedicine.
The biomaterials aiming to repair soft tissue or skin must restore function, initiate or accelerate wound healing, reduce pain, and help achieve the desired cure while also allowing for the correct tissue repair, at least in anatomical terms. Today, a priority is to design biomaterials that are bioactive and can lead to a regenerative process in the recipient tissue. It is important that the type of scaffold and conditions should be adequate to support the proliferation and differentiation of the particular cell type used.[98]
These strategies are centered on the creation of scaffolds that are biochemically and structurally similar to the natural extracellular matrix, providing treatment options in case of acute and chronic wounds, including burns. These new treatments are focused to facilitate skin regeneration and wound healing. There are different types of scaffolds made of natural and synthetic polymers such as films, sponges, and micro- and nano-fibers [Figure 1]. Multiple manufacturing techniques have been used, such as polyanion complexation, layer-by-layer assembly, electrodeposition, autoassembly, phase separation, microcontact printing, crosslinking, grafting, and synthesis of templates to produce nanofibers.[21],[35] [Table 3] describes the different strategies that have been used and their biomedical applications aimed at repairing injured soft tissues. | Figure 1: Representative images of the different types of scaffolds used in tissue engineering using biomaterials synthesized in this case from chitosan
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| Discussion | | |
This work is a particular review of the recent literature on biomaterials, the objective of which is to give a current panoramic view of their main uses and designs in repairing and restoring several kinds of tissues. Many of these new biomaterials were developed not only to fill gaps in effective therapies for certain clinical problems but also to reduce costs and improve the clinical results obtained with other medical materials that lack the desired biological interactions between the host and implanted biomaterial. The vast majority of the research carried out in the development of these new tissue engineering technologies achieved promising results. Nevertheless, they were lacking in clinical studies comparing the effectiveness shown in animal models to that in human patients. This void of information provides numerous opportunities for further research, and this review represents an improvement from similar articles because the most recent research on biomaterials is listed on simple tables ordered by tissue, year, and specific application in translational sciences. The presentation through tables offers an analytical comparison between each study, giving the main advantages, disadvantages, and current clinical trials in the field. The review brings a clear and complete perspective on state of the art in biomaterials and how it will advance in the future. The division between three main tissues (bone, neural, and soft tissue) is carried out because these are the most notable and challenging areas for biomedical application, due to their particular high demand and complexity with regard to regenerative medicine. It is imperative in many surgical areas to find biocompatible substitutes representing an attractive cost-benefit option that will lead to better clinical outcomes and better quality of life for the patient.
Nowadays, one of the most frequently studied cases of tissue engineering is the use of biomaterials for bone regeneration; the current research often focuses on the development of biocompatible osteoconductive and osteoinductive scaffolds that permit directed and effective bone regeneration, primarily for orthopedic and maxillofacial procedures, as shown in [Table 1]. Several biomaterials have been studied alone and in combination, and the majority are in vitro and in animal models, where they displayed different characteristics. The increased research for improved and effective biomaterials in bone regeneration, exits due to the limitations in the use of autologous bone graft, considred the gold standard for this kind of procedures. Bone grafts at times present serious problems in clinical settings, mostly because of the relatively small amount that can be harvested from a patient and the concomitant comorbidities and complications related to this procedure. Other options have been used to address these problems, such as the application of allografts and xenografts, the former having high manufacturing-related costs and low but latent risks of infectious disease transmission and rejection. On the other hand, the xenografts are a less expensive option but generally lack osteogenic activity.
Hydroxyapatite is an excellent scaffold option and one of the most extensively used biomaterials for bone regeneration due to its absence in inflammatory response and long resorption time. Its main disadvantages are fragility and reduced mechanical resistance, problems that are dealt with by the development of composites that combine the properties and advantages of two different biomaterials. An example is that of chitosan, where an important improvement in moldability and osteoconductive properties has been achieved.[49],[50],[51],[52],[53],[54],[55],[56] Bone cement has also been employed to increase compression strength,[57] or the use of a third component such as collagen has been studied, with resulting increase in tensile strength and flexibility.[58] Other methods used to improve the effectiveness of these biomaterials are the loading of bioactive substances into the scaffold, resulting in the improvement of osteoinductive characteristics.[59],[60] Recently, several new forms of hydroxyapatite-chitosan composites have been developed, including nanotubes,[61] carboxymethyl chitosan,[62] and the combination of an apatite-wollastonite-magnetic glass ceramic with chitosan,[63] but have only brought slight new benefits. The design of synthetic materials with improved flexibility, such as poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)/nano-hydroxyapatite,[64] has been useful for guided bone regeneration. The use of chitosan-only-based materials or in combination with β-tricalcium phosphate [65],[66] has demonstrated good intrinsic properties of chitosan for osteoconductivity. Currently, research is centered around the combination of these scaffolds with stem cells that could be induced to differentiate into osteoblasts,[67] the synthesis of new and more moldable biomaterials for surgery in form of gelatins,[68] the hydrogels alone,[69] the loaded materials with BMP-2 proteins,[70],[71] or in the making of novel combinations such as with a xylan hemicellulose/chitosan composite hydrogel.[72]
Further outstanding advantages of these bone biomaterials are that they are more available and have reduced manufacturing costs compared to the current gold standard. Furthermore, the synthesis of injectable hydrogels and drug-loaded scaffolds make these biomaterials attractive as future options for surgeons and patients. However, the risks and side effects of these biomaterials have not been firmly established in clinical trials although the potential side effects found in animal models have been related with inflammation of the surgical zone and the intrinsic risks of infection that can occur during any surgery.
In case of nervous tissue, chitosan has shown promising results, due to its excellent capacity of personalized designs, biodegradability, biocompatibility, antimicrobial properties, and angiogenic stimulation.[74] Even the degradation products of chitosan have shown promotion of nervous tissue regeneration; one of the main properties of this biomaterial is that this regenerative effect is constant in pathologic states, such as in diabetes.[75] The most prominent biomaterials used in nervous tissue repair, together with their different characteristics, are presented in [Table 2].
One of the main disadvantages of chitosan is its low resistance and durability in physiological conditions. Because of this intrinsic labile nature, it is difficult for chitosan to keep its shape, therefore limiting its use. This has been improved with the combination of chitosan with other materials, such as glycidyloxypropyltrimethoxysilane,[74] montmorillonite/poly(vinyl alcohol),[76] and hyaluronic acid hydrogels.[77] It has also been reported that there is a potential host inflammatory response proportional to the material porosity perhaps as a consequence of the large contact surface interaction with the immune system.
Other materials used for nerve regeneration are carbon nanotubes despite that direct contact with neuronal cells can cause cytotoxicity. However, in combination with phosphate glass fiber,[78] polyvinyl alcohol membranes,[79] or polydimethylsiloxane plates,[80] this cytotoxicity could be decreased as a consequence of longer release times and less solubility produced by the improved mechanical and chemical properties of the composite. It is also important to mention the improvement in electric conductivity and functional nerve regeneration.[78]
Other materials such as polylactic-co-glycolic acid,[81] porous sheet of poly(DL-lactic acid),[82] soft Ca-alginate NaCl hydrogels, and porous zein microtubules [83] have demonstrated good mechanical resistance, easy manufacturing, and low or inexistent toxicity. They also offer a convenient microenvironment for cell proliferation and migration, ascribed to its controlled and slow degradation.
In addition, there are new innovative trends in research, for instance the use of combinations of stem cells in printed structures of poly (methacrylamide) gels, bioactive graphene nanoplatelets,[84] peptidic scaffolds alone or with injectable peptidic materials doped with superparamagnetic iron oxide nanoparticles that prompt ordered and guided cell growth.
In the area of soft tissue repair, there are many reported studies in the literature of an abdominal mesh using mostly polypropylene and chitosan; both of them showing less formation of adhesions,[97] decreased inflammatory response,[99] higher resistance to traction,[101] and diminished costs.[102] The most recent biomaterials for soft tissue are summarized in [Table 3]. There are reports of mesh applications for other tissues, such as pelvic soft tissue,[109],[110],[111] skin,[112] and pulmonary valves.[114] It is important to mention that in the case of soft tissue there are two clinical studies, one is for a collagen mesh that is programmed to be used in geriatric patients [115] and the other for a polyacrylate-polyalcohol copolymer used in endoscopic surgery for vesicoureteral reflux. Notwithstanding, in the first study, only one patient was enrolled and in the second a small number of patients were tested with these biomaterials; new strategies in the scaffolds and displays designs have been proposed, from 3D models to piezoelectric actuators, that surely will improve the design of new devices in the future.[124],[125],[126] The preliminary results showed good functionality and biocompatibility. Further research is necessary for clinical settings to establish the real advantages of this promising field of medicine.
| Conclusion | | |
The development of new improved biomaterials is crucial in the field of regenerative medicine; this will allow the construction of improved strategies that will provide better medical and surgical solutions for patients. Therefore, it is important to put together all possible efforts, knowledge, and capabilities from different disciplines within the physical sciences related to these topics in pursuance of the development of biomaterials and their use in tissue engineering. The finding of effective treatments for regeneration and/or repair of injured or harmed tissue, as well as improving or enhancing the functionality of a given organ and/or tissue, or its total replacement, will ultimately extend the quality of life of patients who have such problems. All of this is possible because of the effective association between basic research and clinical situations. This work with a translational approach should be the goal of health systems all over the world where collaboration is no longer as a dream, but as a tangible reality that expresses the idea, “from the laboratory bench to the patient.”
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Acknowledgment
We wish to thank Cesar García for his support in the English review.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1], [Table 2], [Table 3]
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