|Year : 2020 | Volume
| Issue : 6 | Page : 692-699
|Scaffolds— The Ground for Regeneration: A Narrative Review
Sourabh Ramesh Joshi1, Gowri Swaminatham Pendyala2, Pratima Shah1, Viddyasagar Prabhakar Mopagar1, Neeta Padmawar1, Meghana Padubidri1
1 Department of Pediatric & Preventive Dentistry, Rural Dental College, Loni, Maharashtra, India
2 Department of Peridontics, Rural Dental College, Loni, Maharashtra, India
|Date of Submission||20-Apr-2020|
|Date of Decision||02-May-2020|
|Date of Acceptance||16-Oct-2020|
|Date of Web Publication||23-Nov-2020|
Dr. Sourabh Ramesh Joshi
Department of Pediatric & Preventive Dentistry, Rural Dental College, Loni 413736, Maharashtra.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aim: The aim of this study was to comprehensively review the various biomaterials used as scaffolds, rates of biodegradability of natural, artificial and composite hybrid scaffolds, and the role of controlled biodegradability in tissue engineering. Materials and Methods: An electronic search for systematic review was conducted in PubMed/MEDLINE (www.ncbi.nlm.nih.gov), Cochrane (www.cochrane.org), Scopus (www.scopus.com) databases, and dental journals related to endodontics and pediatric dentistry to identify the research investigations associated with the degradation profiles, factors relating to degradation, rates of biodegradability and the role of controlled biodegradability of natural, artificial and composite scaffolds. A sample of 17 relevant studies and case reports were identified in our search of 100 using simple random sampling. Results: Naturally derived scaffolds degrade at a much higher rate than artificial and composite scaffolds. The degradation profiles of composite scaffolds can be much better controlled than naturally derived scaffolds. Conclusion: Composite scaffolds are more favorable as compared to natural or artificial scaffolds, as it has superior mechanical properties, minimal immune response, and a controlled rate of degradation and consequent tissue regeneration.
Keywords: Artificial, degradation profiles, natural, scaffolds, tissue engineering
|How to cite this article:|
Joshi SR, Pendyala GS, Shah P, Mopagar VP, Padmawar N, Padubidri M. Scaffolds— The Ground for Regeneration: A Narrative Review. J Int Soc Prevent Communit Dent 2020;10:692-9
|How to cite this URL:|
Joshi SR, Pendyala GS, Shah P, Mopagar VP, Padmawar N, Padubidri M. Scaffolds— The Ground for Regeneration: A Narrative Review. J Int Soc Prevent Communit Dent [serial online] 2020 [cited 2021 Mar 8];10:692-9. Available from: https://www.jispcd.org/text.asp?2020/10/6/692/300930
| Introduction|| |
People and animals have a natural scaffold that surrounds cells and provides structural support for the formation of tissues and organs. Tissue engineering is a discipline that collaborates cell behavior and the technique of growing them on a substrate known as the “scaffold” along with suitable biochemical factors that promote regeneration. Scaffolds are designed to create a 3D environment that promotes tissue development of cells that are placed on or within the scaffold., One of the most important properties of a scaffold is its biodegradability. The degradation timeline of a scaffold is very important and should closely follow the rate of tissue regeneration. When taking into consideration natural scaffolds, they may degrade before the tissue regeneration occurs. However with synthetic materials, it must be considered that the release of acidic products will reduce the pH of the surrounding tissues and will thereby affect the tissues. Some of the other applications in dentistry include regenerative endodontic procedures, guided tissue regeneration in the field of periodontics, and correction of disease affected temporo mandibular joint.
This narrative review aimed to describe the various biomaterials used as scaffolds, rates of biodegradability of natural, artificial and composite hybrid scaffolds, and the role of controlled biodegradability in tissue engineering.
| Materials and Methods|| |
Articles for this systematic review were searched using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
For deciding the inclusion criteria, the PICOS Guidelines were followed.[Annexure Table 1] shows the strategy for deciding the inclusion criteria, which were as follows: (1) randomized controlled trials, prospective and retrospective studies, (2) studies (in vivo and in vitro) that evaluated degradation profiles, factors relating to degradation, rates of biodegradability, role of controlled biodegradability of natural, artificial and composite scaffolds, (3) studies published in the English language, and (4) animal studies.
Exclusion criteria of the study included any letters to editor, reviews, abstracts, and article published in foreign language.
The outcomes of this review were to assess rates of biodegradability of natural, artificial and composite hybrid scaffolds, the role of controlled biodegradability in tissue engineering, and as to which scaffold works best in dentistry.
Strategy of search
An electronic search for the narrative review was conducted in PubMed/MEDLINE (www.ncbi.nlm.nih.gov), Cochrane (www.cochrane.org), and Scopus (www.scopus.com) databases to identify studies related to the degradation profiles, factors relating to degradation, rates of biodegradability, and the role of controlled biodegradability of natural, artificial, and composite scaffolds. The search structure followed the pediatric and endodontics journals: Dental Traumatology, International Journal of Pediatric Dentistry, Pediatric Dentistry, Journal of Endodontics, International Endodontic Journal, Journal of American Dental Association, and Australian Endodontic Journal. The keywords included were as follows: “tissue engineering,” “scaffolds,” “degradation profiles,” “natural,” and “artificial.” The search includes all the articles from start date of each source until February 15, 2020 [Annexure Table 1] and [Annexure Table 2]. The articles searched were selected based on the quality of literature.
Risk of bias
Cochrane Collaboration’s Tool for Assessing Risk of Bias in Randomized Trials was used to evaluate the risk of bias. Critical assessments were made separately for different domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. For each domain, the risk of bias was graded as high, low, or unclear based on criteria described in the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0.
Various biomaterials both natural and artificial scaffolds that are most commonly used have been described briefly as follows [Annexure Table 3].,,,,,,,,
Composite materials with polymeric matrices also defined as polymer-based composite materials have emerged as suitable candidates for load-bearing applications in several fields. For example, polymer materials lack adequate stiffness. Addition of stiff materials such as glasses and ceramic overcomes the inherent weakness of polymers making it suitable for dental tissue regeneration.
Biodegrability of scaffolds: the concept,
Various groups have stated that degradation of the scaffolds happens due to infiltrating phagocytes. Phagocytes adhere to the scaffold and synthesize large amounts of hydrolytic enzymes. Macrophages are the predominant cells and remain present at the biomaterial interface until the degradation process is finalized. In the presence of large scaffold remnants, macrophages fuse to form foreign body giant cells (FBGCS) and undertake phagocytosis. Ultimately, they release large quantities of ROS, degradative enzymes, and acids in the final attempt to break down the scaffold.
| Results|| |
From the characteristic table [Annexure Table 4], it was clear that naturally derived scaffolds degrade at a much higher rate than artificial and composite scaffolds. The degradation profiles of composite and synthetic scaffolds can be better controlled than naturally derived scaffolds. A sample of 17 relevant studies was identified in our search of 100. The variables were authors/journal, type of study, scaffolds considered, tests used, and conclusion.
| Discussion|| |
In this narrative review, all in vitro, in vivo animal models as well as case reports were included. The aim was to evaluate the literature to describe biodegradation as an individual property, and the rate of degradation of commonly used scaffolds. Our article also described the various natural, artificial, and composite scaffolds commonly used. In all of the records evaluated, the method of measurement of biodegradability was done by two of the following methods: either by measuring mass loss in in vitro studies or by histologic evaluation at certain intervals in in vivo study models. In in vitro testing, testing is done according to ISO 10993-14: 2009.
In most of our evaluated studies, PBS (phosphate buffered saline) or SBF (simulated body fluids) were the solutions used. The samples were placed in a closed test tube in either of these solutions at 37°C. Mass loss was measured after washing with deionized water and dehydration.,,,
Among synthetic membranes, the degradation rate is relatively slow (12–24 months). Naturally derived membranes without cross-linking show a rapid degradation profile of approximately 7–10 days. Cross-linked membranes show a slow rate of degradation. Controlled degradation was seen with Mg-based bioceramics doped with Zn or Cu ions. The samples doped with Cu showed a faster rate of degradation as well as consequent hydroxyapatite formation as compared to the Zn doped samples. Another example of controlled degradation of natural scaffolds was given by Park et al., who concluded that aqueous silk fibroin scaffolds showed 95% mass loss. However, the scaffolds prepared with hexaflouroisopropanol (HFIP) showed only 7% mass loss after dehydration, which showed that HFIP could be used to control and slow the rate of degradation of silk fibroin scaffolds.
| Conclusion|| |
From the above narrative review, it is clear that composite scaffolds are more favorable as they have superior mechanical properties, minimal immune response, and a controlled rate of degradation and consequent tissue regeneration.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Ethical policy and institutional review board statement
Patient declaration of consent
Data availability statement
| References|| |
Murray PE. Constructs and scaffolds employed to regenerate dental tissue. Dent Clin North Am 2012;56:577-88.
Sharma S, Srivastava D, Grover S, Sharma V. Biomaterials in tooth tissue engineering: A review. J Clin Diagn Res 2014;8:309-15.
Zhu J. Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 2010;31:4639-56.
Barre A, Naudot M, Colin F, Sevestre H, Collet L, Devauchelle B, et al
. An alginate-based hydrogel with a high angiogenic capacity and a high osteogenic potential. Biores Open Access 2020;9:174-82.
Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Reprint - Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther2009;89:873-80.
Methley AM, Campbell S, Chew-Graham C, McNally R, Cheraghi-Sohi S. PICO, PICOS and SPIDER: A comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res 2014;14:579.
Higgins JP, Thomas J. Cochrane Handbook for Systematic Reviews of Interventions, Version 6; 2019. Chichester: John Wiley & Sons Ltd. Available from: http:// handbook.cochrane.org. [Last accessed date on 10 Jul 2020].
Gathani KM, Raghavendra SS. Scaffolds in regenerative endodontics: A review. Dent Res J 2016;13:379.
] [Full text]
Borie E, Oliví DG, Orsi IA, Garlet K, Weber B, Beltrán V, et al
. Platelet-rich fibrin application in dentistry: A literature review. Int J Clin Exp Med 2015;8:7922.
Chen G, Lv Y. Decellularized bone matrix scaffold for bone regeneration. Methods Mol Biol 2018;1577:239-54.
Gentile P, Chiono V, Carmagnola I, Hatton PV. An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. Int J Mol Sci 2014;15:3640-59.
Kular JK, Basu S, Sharma RI. The extracellular matrix: Structure, composition, age-related differences, tools for analysis and applications for tissue engineering. J Tissue Eng2014;5:2041731414557112.
Galler KM, D’Souza RN, Hartgerink JD, Schmalz G. Scaffolds for dental pulp tissue engineering. Adv Dent Res 2011;23: 333-9.
Wissing TB, Bonito V, van Haaften EE, van Doeselaar M, Brugmans MMCP, Janssen HM, et al
. Macrophage-driven biomaterial degradation depends on scaffold microarchitecture. Front Bioeng Biotechnol 2019;7:87.
Sadtler K, Wolf MT, Ganguly S, Moad CA, Chung L, Majumdar S, et al
. Divergent immune responses to synthetic and biological scaffolds. Biomaterials 2019;192:405-15.
Lam CX, Hutmacher DW, Schantz JT, Woodruff MA, Teoh SH. Evaluation of polycaprolactone scaffold degradation for 6 months in vitro
and in vivo
. J Biomed Mater Res A 2009;90:906-19.
Lundquist R, Dziegiel MH, Agren MS. Bioactivity and stability of endogenous fibrogenic factors in platelet-rich fibrin. Wound Repair Regen 2008;16:356-63.
Park SH, Gil ES, Kim HJ, Lee K, Kaplan DL. Relationships between degradability of silk scaffolds and osteogenesis. Biomaterials 2010;31:6162-72.
Gomes ME, Azevedo HS, Moreira AR, Ellä V, Kellomäki M, Reis RL. Starch-poly(epsilon-caprolactone) and starch-poly(lactic acid) fibre-mesh scaffolds for bone tissue engineering applications: Structure, mechanical properties and degradation behaviour. J Tissue Eng Regen Med 2008;2:243-52.
Kawase T, Kamiya M, Kobayashi M, Tanaka T, Okuda K, Wolff LF, et al
. The heat-compression technique for the conversion of platelet-rich fibrin preparation to a barrier membrane with a reduced rate of biodegradation. J Biomed Mater Res B Appl Biomater 2015;103:825-31.
Singhal AR, Agrawal CM, Athanasiou KA. Salient degradation features of a 50:50 PLA/PGA scaffold for tissue engineering. Tissue Eng 1996;2:197-207.
Fu Q, Rahaman MN, Bal BS, Bonewald LF, Kuroki K, Brown RF. Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. II. In vitro
and in vivo
biological evaluation. J Biomed Mater Res A 2010;95:172-9.
Theodorou GS, Kontonasaki E, Theocharidou A, Bakopoulou A, Bousnaki M, Hadjichristou C, et al
. Sol-gel derived mg-based ceramic scaffolds doped with zinc or copper ions: Preliminary results on their synthesis, characterization, and biocompatibility. Int J Biomater 2016;2016:3858301.
Hafeman AE, Li B, Yoshii T, Zienkiewicz K, Davidson JM, Guelcher SA. Injectable biodegradable polyurethane scaffolds with release of platelet-derived growth factor for tissue repair and regeneration. Pharm Res 2008;25:2387-99.
Smidt A, Gutmacher Z, Sharon E. A nouveau collagen scaffold to simplify lateral augmentation of deficient ridges between natural teeth. Quintessence Int 2019;50:576-82.
Moses O, Vitrial D, Aboodi G, Sculean A, Tal H, Kozlovsky A, et al
. Biodegradation of three different collagen membranes in the rat calvarium: A comparative study. J Periodontol 2008;79:905-11.
Kozlovsky A, Aboodi G, Moses O, Tal H, Artzi Z, Weinreb M, et al
. Bio-degradation of a resorbable collagen membrane (bio-gide) applied in a double-layer technique in rats. Clin Oral Implants Res 2009;20:1116-23.
Gilbert TW, Stewart-Akers AM, Badylak SF. A quantitative method for evaluating the degradation of biologic scaffold materials. Biomaterials 2007;28:147-50.
Wang Y, Rudym DD, Walsh A, Abrahamsen L, Kim HJ, Kim HS, et al
. In vivo
degradation of three-dimensional silk fibroin scaffolds. Biomaterials 2008;29: 3415-28.
Shah SS, Liang H, Pandit S, Parikh Z, Schwartz JA, Goldstein T, et al
. Optimization of degradation profile for new scaffold in cartilage repair. Cartilage 2018;9: 438-49.
Magno MHR, Kim J, Srinivasan A, McBride S, Bolikal D, Darr A, et al
. Synthesis, degradation and biocompatibility of tyrosine-derived polycarbonate scaffolds. J Mater Chem 2010;20:8885-93.
Mobini S, Taghizadeh-Jahed M, Khanmohammadi M, Moshiri A, Naderi M-M, Heidari-Vala H, et al
. Comparative evaluation of in vivo
biocompatibility and biodegradability of regenerated silk scaffolds reinforced with/without natural silk fibers. J Biomater Appl 2016;30:793-809.