Scaffolds— The Ground for Regeneration: A Narrative Review

Abstract

INTRODUCTION People and animals have a natural scaffold that surrounds cells and provides structural support for the formation of tissues and organs.[1] 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.[2] Scaffolds are designed to create a 3D environment that promotes tissue development of cells that are placed on or within the scaffold.[34] 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.[5] ELIGIBILITY CRITERIA For deciding the inclusion criteria, the PICOS Guidelines were followed.[6]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.Table 1: PICOS guidelinesExclusion criteria of the study included any letters to editor, reviews, abstracts, and article published in foreign language. OUTCOME 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 Information sources 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 Tables 1 and 2]. The articles searched were selected based on the quality of literature.Table 2: Search strategyRISK OF BIAS Cochrane Collaboration’s Tool for Assessing Risk of Bias in Randomized Trials was used to evaluate the risk of bias.[7] 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.[7] Various biomaterials both natural and artificial scaffolds that are most commonly used have been described briefly as follows [Annexure Table 3].[1238910111213]Table 3: Characteristics of natural and artificial scaffoldsCOMPOSITE SCAFFOLDS Composite materials with polymeric matrices also defined as polymer-based composite materials have emerged as suitable candidates for load-bearing applications in several fields.[2] 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[14,15] 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.Table 4: Characteristic tableDISCUSSION 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.[16] 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.[16171819] Among synthetic membranes, the degradation rate is relatively slow (12–24 months).[20] 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.,[18] 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 Nil. CONFLICTS OF INTEREST There are no conflicts of interest. AUTHORS CONTRIBUTIONS Not applicable. ETHICAL POLICY AND INSTITUTIONAL REVIEW BOARD STATEMENT Not applicable. PATIENT DECLARATION OF CONSENT Not applicable. DATA AVAILABILITY STATEMENT Not applicable. ACKNOWLEDGEMENT Not applicable.

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