|Year : 2017 | Volume
| Issue : 4 | Page : 85-102
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|
Department of Neurosciences, University Center of Health Sciences, Translational Neurosciences Institute, University of Guadalajara, 44340 Guadalajara, Jalisco
Source of Support: None, Conflict of Interest: None
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 2019 Aug 23];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.,,, 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.,, 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.
| 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.,,,,,
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.,,, 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.,,, 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.,, 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.,,,
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.,,, 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. ,,,,
The current strategies of regenerative medicine focus on the reestablishment of functional and morphological architecture of pathologically altered tissues.,,,, 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.,,,,,,
| 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. [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. [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.
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., [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|
Click here to view
| 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.,,,,,,, Bone cement has also been employed to increase compression strength, or the use of a third component such as collagen has been studied, with resulting increase in tensile strength and flexibility. 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., Recently, several new forms of hydroxyapatite-chitosan composites have been developed, including nanotubes, carboxymethyl chitosan, and the combination of an apatite-wollastonite-magnetic glass ceramic with chitosan, 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, has been useful for guided bone regeneration. The use of chitosan-only-based materials or in combination with β-tricalcium phosphate , 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, the synthesis of new and more moldable biomaterials for surgery in form of gelatins, the hydrogels alone, the loaded materials with BMP-2 proteins,, or in the making of novel combinations such as with a xylan hemicellulose/chitosan composite hydrogel.
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. 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. 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, montmorillonite/poly(vinyl alcohol), and hyaluronic acid hydrogels. 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, polyvinyl alcohol membranes, or polydimethylsiloxane plates, 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.
Other materials such as polylactic-co-glycolic acid, porous sheet of poly(DL-lactic acid), soft Ca-alginate NaCl hydrogels, and porous zein microtubules  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, 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, decreased inflammatory response, higher resistance to traction, and diminished costs. 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,,, skin, and pulmonary valves. 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  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.,, 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.
We wish to thank Cesar García for his support in the English review.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
James R, Laurencin CT. The Evolution and Application of Regenerative Engineering. In MRS Proceedings. Cambridge University Press; 2014.
Williams DF. On the nature of biomaterials. Biomaterials
Rodriguez-Vazquez M, Vega-Ruiz B, Ramos-Zuniga R, Saldana-Koppel DA, Quinones-Olvera LF. Chitosan and its potential use as a scaffold for tissue engineering in regenerative medicine. Biomed Res Int
Dhandayuthapani B, Yoshida Y, Maekawa T, Kumar DS. Polymeric scaffolds in tissue engineering application: A review. Int J Polym Sci
Shi C, Zhu Y, Ran X, Wang M, Su Y, Cheng T. Therapeutic potential of chitosan and its derivatives in regenerative medicine. J Surg Res
Fung Y. A proposal to the national science foundation for an engineering research centre at USCD. Cent Eng Living Tissues UCSD 2001;2001(1):865023.
Langer R, Vacanti JP. Tissue engineering. Science
Kirkpatrick CJ. Modelling the regenerative niche: A major challenge in biomaterials research. Regen Biomater
Liu AP, Chaudhuri O, Parekh SH. New advances in probing cell-extracellular matrix interactions. Integr Biol (Camb)
Woolman M, Gribble A, Bluemke E, Zou J, Ventura M, Bernards N, Wu M, Ginsberg HJ, Das S, Vitkin A, Zarrine-Afsar A. Optimized mass spectrometry analysis workflow with polarimetric guidance for ex vivo
and in situ
sampling of biological tissues. Sci Rep
do Nascimento MH, Ferreira M, Malmonge SM, Lombello CB. Evaluation of cell interaction with polymeric biomaterials based on hyaluronic acid and chitosan. J Mater Sci Mater Med
He Z, Santos JL, Tian H, Huang H, Hu Y, Liu L, Leong KW, Chen Y, Mao HQ. Scalable fabrication of size-controlled chitosan nanoparticles for oral delivery of insulin. Biomaterials
Guarnieri V, Biazi L, Marchiori R, Lago A. Platinum metallization for MEMS application. Focus on coating adhesion for biomedical applications. Biomatter
Felix SH, Shah KG, Tolosa VM, Sheth HJ, Tooker AC, Delima TL, Jadhav SP, Frank LM, Pannu SS. Insertion of flexible neural probes using rigid stiffeners attached with biodissolvable adhesive. J Vis Exp
Kalamarz-Kubiak H. Conference scene: The 2015 tissue engineering congress, London, UK, 8-10 September 2015. Regen Med
Tabatabaei FS, Torshabi M.In vitro
proliferation and osteogenic differentiation of endometrial stem cells and dental pulp stem cells. Cell Tissue Bank
Gonzalez-Perez F, Cobianchi S, Heimann C, Phillips JB, Udina E, Navarro X. Stabilization, rolling, and addition of other extracellular matrix proteins to collagen hydrogels improve regeneration in chitosan guides for long peripheral nerve gaps in rats. Neurosurgery
Long R, Liu Y, Wang S, Ye L, He P. Co-microencapsulation of BMSCs and mouse pancreatic beta cells for improving the efficacy of type I diabetes therapy. Int J Artif Organs
Lee WD, Gawri R, Shiba T, Ji AR, Stanford WL, Kandel RA. Simple silica column-based method to quantify inorganic polyphosphates in cartilage and other tissues. Cartilage
Wang Y, Wang K, Li X, Wei Q, Chai W, Wang S, Che Y, Lu T, Zhang B. 3D fabrication and characterization of phosphoric acid scaffold with a HA/beta-TCP weight ratio of 60: 40 for bone tissue engineering applications. PLoS One
Guo T, Holzberg TR, Lim CG, Gao F, Gargava A, Trachtenberg JE, Mikos AG, Fisher JP. 3D printing PLGA: A quantitative examination of the effects of polymer composition and printing parameters on print resolution. Biofabrication
Brigo L, Urciuolo A, Giulitti S, Della Giustina G, Tromayer M, Liska R, Elvassore N, Brusatin G. 3D high-resolution two-photon crosslinked hydrogel structures for biological studies. Acta Biomater
Salazar GT, Ohneda O. Review of biophysical factors affecting osteogenic differentiation of human adult adipose-derived stem cells. Biophys Rev
Cheng H, Chawla A, Yang Y, Li Y, Zhang J, Jang HL, Khademhosseini A. Development of nanomaterials for bone-targeted drug delivery. Drug Discov Today
Rodrigues JR, Alves NM, Mano JF. Nacre-inspired nanocomposites produced using layer-by-layer assembly: Design strategies and biomedical applications. Mater Sci Eng C Mater Biol Appl
Kelly SH, Shores LS, Votaw NL, Collier JH. Biomaterial strategies for generating therapeutic immune responses. Adv Drug Deliv Rev
Lasa BV, del Barrio JS, Bravo AL, Ruiz AG. Tissue engineering”: Contribution of polymers to the development of the processes of tissue regeneration. In: Annals of the Royal Spanish Society of Chemistry. Royal Spanish Society of Chemistry. 2000.
Novitsky YW, Porter JR, Rucho ZC, Getz SB, Pratt BL, Kercher KW, Heniford BT. Open preperitoneal retrofascial mesh repair for multiply recurrent ventral incisional hernias. J Am Coll Surg
Han S, Chen Z, Han P, Hu Q, Xiao Y. Activation of macrophages by lipopolysaccharide for assessing the immunomodulatory property of biomaterials. Tissue Eng Part A
Rahn S, Bahr M, Schalamon J, Saxena AK. Single-center 10-year experience in the management of anterior abdominal wall defects. Hernia
Muzzarelli RA, Mattioli-Belmonte M, Pugnaloni A, Biagini G. Biochemistry, histology and clinical uses of chitins and chitosans in wound healing. EXS
Wu T, Zivanovic S, Draughon FA, Conway WS, Sams CE. Physicochemical properties and bioactivity of fungal chitin and chitosan. J Agric Food Chem
Madihally SV, Matthew HW. Porous chitosan scaffolds for tissue engineering. Biomaterials
Hong SC, Yoo SY, Kim H, Lee J. Chitosan-based multifunctional platforms for local delivery of therapeutics. Marine Drugs
Venkatesan J, Anil S, Kim SK, Shim MS. Chitosan as a vehicle for growth factor delivery: Various preparations and their applications in bone tissue regeneration. Int J Biol Macromol
2017;104 (Pt B):1383-97.
Lu Z, Chen Y, Dunstan C, Roohani-Esfahani S, Zreiqat H. Priming adipose stem cells with tumor necrosis factor-alpha preconditioning potentiates their exosome efficacy for bone regeneration. Tissue Engineering Part A
Petrenko Y, Syková E, Kubinová Š. The therapeutic potential of three-dimensional multipotent mesenchymal stromal cell spheroids. Stem Cell Res Ther
Murphy AR, Laslett A, O'Brien CM, Cameron NR. Scaffolds for 3D in vitro
culture of neural lineage cells. Acta Biomater
Gerhard EM, Wang W, Li C, Guo J, Ozbolat IT, Rahn KM, Armstrong AD, Xia J, Qian G, Yang J. Design strategies and applications of nacre-based biomaterials. Acta Biomater
Shotorbani BB, Alizadeh E, Salehi R, Barzegar A. Adhesion of mesenchymal stem cells to biomimetic polymers: A review. Mater Sci Eng C
Sun SF, Hsu CW, Lin HS, Liou IH, Chen YH, Hung CL. Comparison of Single intra-articular injection of novel hyaluronan (HYA-JOINT Plus) with Synvisc-one for knee osteoarthritis: A Randomized, controlled, double-blind trial of efficacy and safety. J Bone Joint Surg Am
Martins EA, Michelacci YM, Baccarin RY, Cogliati B, Silva LC. Evaluation of chitosan-GP hydrogel biocompatibility in osteochondral defects: An experimental approach. BMC Vet Res
Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Restrepo A, Shive MS. Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. J Bone Joint Surg Am
Lin LX, Yuan F, Zhang HH, Liao NN, Luo JW, Sun YL. Evaluation of surgical anti-adhesion products to reduce postsurgical intra-abdominal adhesion formation in a rat model. PLoS One
Zhou T, Sui B, Mo X, Sun J. Multifunctional and biomimetic fish collagen/bioactive glass nanofibers: Fabrication, antibacterial activity and inducing skin regeneration in vitro
and in vivo
. Int J Nanomedicine
Echave MC, Saenz del Burgo L, Pedraz JL, Orive G. Gelatin as biomaterial for tissue engineering. Curr Pharm Des
Oshikawa M, Okada K, Kaneko N, Sawamoto K, Ajioka I. Affinity-immobilization of VEGF on laminin porous sponge enhances angiogenesis in the ischemic brain. Adv Healthc Mater
Hosseinpour S, Ghazizadeh Ahsaie M, Rezai Rad M, Baghani MT, Motamedian SR, Khojasteh A. Application of selected scaffolds for bone tissue engineering: A systematic review. Oral Maxillofac Surg
Zhao F, Yin Y, Lu WW, Leong JC, Zhang W, Zhang J, Zhang M, Yao K. Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds. Biomaterials
Yoshida A, Miyazaki T, Ishida E, Ashizuka M. Preparation of bioactive chitosan-hydroxyapatite nanocomposites for bone repair through mechanochemical reaction. Mater Trans
Yuan H, Chen N, Lü X, Zheng B. Experimental study of natural hydroxyapatite/chitosan composite on reconstructing bone defects. J Nanjing Med Univ
Xianmiao C, Yubao L, Yi Z, Li Z, Jidong L, Huanan W. Properties and in vitro
biological evaluation of nano-hydroxyapatite/chitosan membranes for bone guided regeneration. Mater Sci Eng C
Liu J, Shi F, Yu L, Niu L, Gao S. Synthesis of chitosan-hydroxyapatite composites and its effect on the properties of bioglass bone cement. J Mater Sci Technol
Li H, Zhou CR, Zhu MY, Tian JH, Rong JH. Preparation and characterization of homogeneous hydroxyapatite/chitosan composite scaffolds via in-situ
hydration. J Biomater Nanobiotechnol
Zhang J, Liu G, Wu Q, Zuo J, Qin Y, Wang J. Novel mesoporous hydroxyapatite/chitosan composite for bone repair. J Bionics Eng
Pu XM, Yao QQ, Yang Y, Sun ZZ, Zhang QQ.In vitro
degradation of three-dimensional chitosan/apatite composite rods prepared via in situ
precipitation. Int J Biol Macromol
Kim SB, Kim YJ, Yoon TL, Park SA, Cho IH, Kim EJ, Kim IA, Shin JW. The characteristics of a hydroxyapatite-chitosan-PMMA bone cement. Biomaterials
Teng SH, Lee EJ, Wang P, Shin DS, Kim HE. Three-layered membranes of collagen/hydroxyapatite and chitosan for guided bone regeneration. J Biomed Mater Res B Appl Biomater
Wu T, Nan K, Chen J, Jin D, Jiang S, Zhao P, Xu J, Du H, Zhang X, Li J. A new bone repair scaffold combined with chitosan/hydroxyapatite and sustained releasing icariin. Chin Sci Bull
Lee M, Li W, Siu RK, Whang J, Zhang X, Soo C, Ting K, Wu BM. Biomimetic apatite-coated alginate/chitosan microparticles as osteogenic protein carriers. Biomaterials
Venkatesan J, Qian ZJ, Ryu B, Kumar NA, Kim SK. Preparation and characterization of carbon nanotube-grafted-chitosan–natural hydroxyapatite composite for bone tissue engineering. Carbohydr Polym
Budiraharjo R, Neoh KG, Kang ET. Hydroxyapatite-coated carboxymethyl chitosan scaffolds for promoting osteoblast and stem cell differentiation. J Colloid Interface Sci
Li C, Wang GX, Zhang Z, Liu DP. Biocompatibility and in vivo
osteogenic capability of novel bone tissue engineering scaffold AW-MGC/CS. J Orthop Surg Res
Fu S, Ni P, Wang B, Chu B, Peng J, Zheng L, Zhao X, Luo F, Wei Y, Qian Z.In vivo
biocompatibility and osteogenesis of electrospun poly (ε-caprolactone)–poly (ethylene glycol)–poly (ε-caprolactone)/nano-hydroxyapatite composite scaffold. Biomaterials
Mota J, Yu N, Caridade SG, Luz GM, Gomes ME, Reis RL, Jansen JA, Walboomers XF, Mano JF. Chitosan/bioactive glass nanoparticle composite membranes for periodontal regeneration. Acta Biomaterialia
Azevedo A, Sá M, Fook M, Neto PN, Sousa O, Azevedo S, Teixeira M, Costa F, Araújo A. Use of chitosan and β-tricalcium phosphate, alone and in combination, for bone healing in rabbits. J Mater Sci Mater Med
Ye K, Felimban R, Traianedes K, Moulton SE, Wallace GG, Chung J, Quigley A, Choong PF, Myers DE. Chondrogenesis of infrapatellar fat pad derived adipose stem cells in 3D printed chitosan scaffold. PloS One
Nommeots-Nomm A, Labbaf S, Devlin A, Todd N, Geng H, Solanki AK, Tang HM, Perdika P, Pinna A, Ejeian F, Tsigkou O, Lee PD, Esfahani MH, Mitchell CA, Jones JR. Highly degradable porous melt-derived bioactive glass foam scaffolds for bone regeneration. Acta Biomater
Sagar N, Pandey AK, Gurbani D, Khan K, Singh D, Chaudhari BP, Soni VP, Chattopadhyay N, Dhawan A, Bellare JR. In-vivo
efficacy of compliant 3D nano-composite in critical-size bone defect repair: A six month preclinical study in rabbit. PloS One
Fan J, Park H, Lee MK, Bezouglaia O, Fartash A, Kim J, Aghaloo T, Lee M. Adipose-derived stem cells and BMP-2 delivery in chitosan-based 3D constructs to enhance bone regeneration in a rat mandibular defect model. Tissue Eng Part A
Coletta DJ, Ibáñez-Fonseca A, Missana LR, Jammal MV, Vitelli EJ, Aimone M, Zabalza F, Issa JP, Alonso M, Rodríguez-Cabello JC. Bone regeneration mediated by a bioactive and biodegradable ECM-like hydrogel based on elastin-like recombinamers. Tissue Eng
Bush JR, Liang H, Dickinson M, Botchwey EA. Xylan hemicellulose improves chitosan hydrogel for bone tissue regeneration. Polym Adv Technol
Chan KM, Gordon T, Zochodne DW, Power HA. Improving peripheral nerve regeneration: From molecular mechanisms to potential therapeutic targets. Exp Neurol
Simoes M, Gärtner A, Shirosaki Y, da Costa RG, Cortez P, Gartner F, Santos J, Lopes M, Geuna S, Varejão A.In vitro
and in vivo
chitosan membranes testing for peripheral nerve reconstruction. Acta Méd Port
Ahn HS, Hwang JY, Kim MS, Lee JY, Kim JW, Kim HS, Shin US, Knowles JC, Kim HW, Hyun JK. Carbon-nanotube-interfaced glass fiber scaffold for regeneration of transected sciatic nerve. Acta Biomaterialia
Meyer C, Stenberg L, Gonzalez-Perez F, Wrobel S, Ronchi G, Udina E, Suganuma S, Geuna S, Navarro X, Dahlin LB. Chitosan-fi lm enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves. Biomaterials
Peng SW, Li CW, Chiu M, Wang GJ. Nerve guidance conduit with a hybrid structure of a PLGA microfi brous bundle wrapped in a micro/nanostructured membrane. Int J Nanomedicine
Leijs MJ, Villafuertes E, Haeck J, Koevoet WJ, Fernandez-Gutierrez B, Hoogduijn M, Verhaar J, Bernsen M, van Buul G, van Osch G. Encapsulation of allogeneic mesenchymal stem cells in alginate extends local presence and therapeutic function. Eur Cells Mater
Moshayedi P, Nih LR, Llorente IL, Berg AR, Cinkornpumin J, Lowry WE, Segura T, Carmichael ST. Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials
Li RY, Liu ZG, Liu HQ, Chen L, Liu JF, Pan YH. Evaluation of biocompatibility and toxicity of biodegradable poly (DL-lactic acid) films. Am J Transl Res
Matyash M, Despang F, Ikonomidou C, Gelinsky M. Swelling and mechanical properties of alginate hydrogels with respect to promotion of neural growth. Tissue Eng Part C Methods
Zhao Y, Wang Y, Gong J, Yang L, Niu C, Ni X, Wang Y, Peng S, Gu X, Sun C. Chitosan degradation products facilitate peripheral nerve regeneration by improving macrophage-constructed microenvironments. Biomaterials
Wang GW, Yang H, Wu WF, Zhang P, Wang JY. Design and optimization of a biodegradable porous zein conduit using microtubes as a guide for rat sciatic nerve defect repair. Biomaterials
Zhu W, Harris BT, Zhang LG. Gelatin methacrylamide hydrogel with graphene nanoplatelets for neural cell-laden 3D bioprinting. In: Engineering in Medicine and Biology Society (EMBC), 2016 IEEE 38th
Annual International Conference. IEEE; 2016.
Rose JC, Cámara-Torres M, Rahimi K, Köhler J, Möller M, De Laporte L. Nerve cells decide to orient inside an injectable hydrogel with minimal structural guidance. Nano Lett
Jiao G, Lou G, Mo Y, Pan Y, Zhang Z, Guo R, Li Z. A combination of GDNF and hUCMSC transplantation loaded on SF/AGs composite scaffolds for spinal cord injury repair. Mater Sci Eng C
Hyysalo A, Ristola M, Joki T, Honkanen M, Vippola M, Narkilahti S. Aligned poly(ε-caprolactone) nanofibers guide the orientation and migration of human pluripotent stem cell-derived neurons, astrocytes, and oligodendrocyte precursor cells in vitro
. Macromol Biosci
Ghasemi Hamidabadi H, Rezvani Z, Nazm Bojnordi M, Shirinzadeh H, Seifalian AM, Joghataei MT, Razaghpour M, Alibakhshi A, Yazdanpanah A, Salimi M. Chitosan-intercalated montmorillonite/ poly (vinyl alcohol) nanofi bers as a platform to guide neuronlike differentiation of human dental pulp stem cells. ACS Appl Mater Interfaces
Requejo-Aguilar R, Alastrue-Agudo A, Cases-Villar M, Lopez-Mocholi E, England R, Vicent MJ, Moreno-Manzano V. Combined polymer-curcumin conjugate and ependymal progenitor/ stem cell treatment enhances spinal cord injury functional recovery. Biomaterials
Ribeiro J, Caseiro AR, Pereira T, Armada-da-Silva PA, Pires I, Prada J, Amorim I, Leal Reis I, Amado S, Santos JD, Bompasso S, Raimondo S, Varejão A, Geuna S, Luís AL, Maurício AC. Evaluation of PVA biodegradable electric conductive membranes for nerve regeneration in axonotmesis injuries: The rat sciatic nerve animal model. J Biomed Mater Res A
Zhang Q, Yan S, You R, Kaplan DL, Liu Y, Qu J, Li X, Li M, Wang X. Multichannel silk protein/laminin grafts for spinal cord injury repair. J Biomed Mater Res Part A
Li LM, Han M, Jiang XC, Yin XZ, Chen F, Zhang TY, Ren H, Zhang JW, Hou TJ, Chen Z, Ou-Yang HW, Tabata Y, Shen YQ, Gao JQ. Peptide-tethered hydrogel scaffold promotes recovery from spinal cord transection via synergism with mesenchymal stem cells. ACS Appl Mater Interfaces
Nune M, Subramanian A, Krishnan UM, Kaimal SS, Sethuraman S. Self-assembling peptide nanostructures on aligned poly (lactide-co-glycolide) nanofibers for the functional regeneration of sciatic nerve. Nanomedicine
Nawrotek K, Marqueste T, Modrzejewska Z, Zarzycki R, Rusak A, Decherchi P. Thermogelling chitosan lactate hydrogel improves functional recovery after a C2 spinal cord hemisection in rat. J Biomed Mater Res A
Terraf P, Kouhsari SM, Ai J, Babaloo H. Tissue-engineered regeneration of hemisected spinal cord using human endometrial stem cells, poly ε-caprolactone scaffolds, and crocin as a neuroprotective agent. Mol Neurobiol
Berkovitch Y, Seliktar D. Semi-synthetic hydrogel composition and stiffness regulate neuronal morphogenesis. Int J Pharm
Wang C, Oh S, Lee HA, Kang J, Jeong KJ, Kang SW, Hwang DY, Lee J. In vivo
feasibility test using transparent carbon nanotube-coated polydimethylsiloxane sheet at brain tissue and sciatic nerve. J Biomed Mater Res A
Lu G, Huang S. Bioengineered skin substitutes: Key elements and novel design for biomedical applications. Int Wound J
Niekraszewicz A, Kucharska M, Wawro D, Struszczyk MH, Rogaczewska A. Partially resorbable hernia meshes. Prog Chem Appl Chitin Derivatives
Gobin AS, Butler CE, Mathur AB. Repair and regeneration of the abdominal wall musculofascial defect using silk fibroin-chitosan blend. Tissue Eng
Burger J, Halm J, Wijsmuller A, ten Raa S, Jeekel J. Evaluation of new prosthetic meshes for ventral hernia repair. Surg Endosc Other Intervent Tech
d'Acampora AJ, Kestering DM, Soldi MS, Rossi LF. Experimental study comparing the tensile strength of different surgical meshes following aponeurotic-muscle deformity synthesis on Wistar rats. Acta Cir Bras
Paulo NM, de Brito e Silva MS, Moraes AM, Rodrigues AP, de Menezes LB, Miguel MP, de Lima FG, de Morais Faria A, Lima LM. Use of chitosan membrane associated with polypropylene mesh to prevent peritoneal adhesion in rats. J Biomed Mater Res Part B Appl Biomater
Ławniczak P, Grobelski B, Pasieka Z. Properties comparison of intraperitoneal hernia meshes in reconstruction of the abdominal wall-animal model study. Pol J Surg
Pascual G, Rodríguez M, Sotomayor S, Moraleda E, Bellón JM. Effects of collagen prosthesis cross-linking on long-term tissue regeneration following the repair of an abdominal wall defect. Wound Repair Regen
Melman L, Jenkins E, Hamilton N, Bender L, Brodt M, Deeken C, Greco S, Frisella M, Matthews B. Histologic and biomechanical evaluation of a novel macroporous polytetrafluoroethylene knit mesh compared to lightweight and heavyweight polypropylene mesh in a porcine model of ventral incisional hernia repair. Hernia
Yuan Y, Zhang J, Yin M, Liu C. Plasma-mediated immobilization of antibody with peg as spacer for enhanced endothelial cell adhesion and proliferation. Adv Biomater
López-Cano M, Armengol M, Quiles MT, Biel A, Velasco J, Huguet P, Mestre A, Delgado LM, Gil FX, Arbós MA. Preventive midline laparotomy closure with a new bioabsorbable mesh: An experimental study. J Surg Res
Udpa N, Iyer SR, Rajoria R, Breyer KE, Valentine H, Singh B, McDonough SP, Brown BN, Bonassar LJ, Gao Y. Effects of chitosan coatings on polypropylene mesh for implantation in a rat abdominal wall model. Tissue Eng Part A
Melnik I, Goldstein D, Yoffe B. Use of a porcine dermal collagen implant for contaminated abdominal wall reconstruction in a 105-year-old woman: A case report and review of the literature. J Med Case Rep
Veleirinho B, Coelho DS, Dias PF, Maraschin M, Pinto R, Cargnin-Ferreira E, Peixoto A, Souza JA, Ribeiro-do-Valle RM, Lopes-da-Silva JA. Foreign body reaction associated with PET and PET/chitosan electrospun nanofi brous abdominal meshes. PloS One
Ghanavati Z, Neisi N, Bayati V, Makvandi M. The influence of substrate topography and biomaterial substance on skin wound healing. Anat Cell Biol
Xuan F, Rong J, Liang M, Zhang X, Sun J, Zhao L, Li Y, Liu D, Li F, Wang X. Biocompatibility and effectiveness evaluation of a new hemostatic embolization agent: Thrombin loaded alginate calcium microsphere. Biomed Res Int
Kluin J, Talacua H, Smits AI, Emmert MY, Brugmans MC, Fioretta ES, Dijkman PE, Söntjens SH, Duijvelshoff R, Dekker S. In situ
heart valve tissue engineering using a bioresorbable elastomeric implant–From material design to 12 months follow-up in sheep. Biomaterials
Lima SV, Machado MR, Pinto FC, Lira MM, Albuquerque AV, Lustosa ES, Silva JG, Campos O Jr. A new material to prevent urethral damage after implantation of artifi cial devices: An experimental study. Int Braz J Urol
Han H, Ning H, Liu S, Lu Q, Fan Z, Lu H, Lu G, Kaplan DL. Silk biomaterials with vascularization capacity. Adv Funct Mater
Ge L, Li Q, Jiang J, You X, Liu Z, Zhong W, Huang Y, Xing MM. Integration of nondegradable polystyrene and degradable gelatinin a core–sheath nanofi brous patch for pelvic reconstruction. Int J Nanomedicine
Turk A, Selimoglu A, Demir K, Celik O, Saglam E, and Tarhan F. Endoscopic treatment of vesicoureteral reflux with polyacrylate polyalcohol copolymer and dextranomer/hyaluronic acid in adults. Int Braz J Urol
Suzuhigashi M, Kaji T, Nakame K, Mukai M, Yamada W, Onishi S, Yamada K, Kawano T, Takamatsu H, Ieiri S. Abdominal wall regenerative medicine for a large defect using tissue engineering: An experimental study. Pediatr Surg Int
Yang X, Wei J, Lei D, Liu Y, Wu W. Appropriate density of PCL nano-fiber sheath promoted muscular remodeling of PGS/PCL grafts in arterial circulation. Biomaterials
Bigozzi MA, Provenzano S, Maeda F, Palma P, Riccetto C.In vivo
biomechanical properties of heavy versus light weight monofilament polypropylene meshes. Does the knitting pattern matter? Neurourol Urodyn
Tchemtchoua VT, Atanasova G, Aqil A, Filée P, Garbacki N, Vanhooteghem O, Deroanne C, Noël A, Jérome C, Nusgens B. Development of a chitosan nanofibrillar scaffold for skin repair and regeneration. Biomacromolecules
Zou Q, Cai B, Li J, Li J, Li Y.In vitro
and in vivo
evaluation of the chitosan/Tur composite film for wound healing applications. J Biomater Sci Polym Ed
Xie X, Zaitsev Y, Velásquez-García LF, Teller S, Livermore C. Scalable, MEMS-enabled, vibrational tactile actuators for high resolution tactile displays. J Micromech Microeng
Xie X, Livermore C. A pivot-hinged, multilayer SU-8 micro motion amplifier assembled by a self-aligned approach. Micro Electro Mech Syst
Xie X, Livermore C. Passively self-aligned assembly of compact barrel hinges for high-performance, out-of-plane MEMS actuators. Micro Electro Mech Syst
[Table 1], [Table 2], [Table 3]