Polymeric Scaffolds for Dental, Oral, and Craniofacial Regenerative Medicine

Dental, oral, and craniofacial (DOC) regenerative medicine aims to repair or regenerate DOC tissues including teeth, dental pulp, periodontal tissues, salivary gland, temporomandibular joint (TMJ), hard (bone, cartilage), and soft (muscle, nerve, skin) tissues of the craniofacial complex. Polymeric materials have a broad range of applications in biomedical engineering and regenerative medicine functioning as tissue engineering scaffolds, carriers for cell-based therapies, and biomedical devices for delivery of drugs and biologics. The focus of this review is to discuss the properties and clinical indications of polymeric scaffold materials and extracellular matrix technologies for DOC regenerative medicine. More specifically, this review outlines the key properties, advantages and drawbacks of natural polymers including alginate, cellulose, chitosan, silk, collagen, gelatin, fibrin, laminin, decellularized extracellular matrix, and hyaluronic acid, as well as synthetic polymers including polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), poly (ethylene glycol) (PEG), and Zwitterionic polymers. This review highlights key clinical applications of polymeric scaffolding materials to repair and/or regenerate various DOC tissues. Particularly, polymeric materials used in clinical procedures are discussed including alveolar ridge preservation, vertical and horizontal ridge augmentation, maxillary sinus augmentation, TMJ reconstruction, periodontal regeneration, periodontal/peri-implant plastic surgery, regenerative endodontics. In addition, polymeric scaffolds application in whole tooth and salivary gland regeneration are discussed.

Chitosan/β-TCP composites scaffolds coated with silk fibroin: a bone tissue engineering approach

Bone regeneration and natural repair are long-standing processes that can lead to uneven new tissue growth. By introducing scaffolds that can be autografts and/or allografts, tissue engineering provides new approaches to manage the major burdens involved in this process. Polymeric scaffolds allow the incorporation of bioactive agents that improve their biological and mechanical performance, making them suitable materials for bone regeneration solutions. The present work aimed to create chitosan/beta-tricalcium phosphate-based scaffolds coated with silk fibroin and evaluate their potential for bone tissue engineering. Results showed that the obtained scaffolds have porosities up to 86%, interconnectivity up to 96%, pore sizes in the range of 60–170 μm, and a stiffness ranging from 1 to 2 MPa. Furthermore, when cultured with MC3T3 cells, the scaffolds were able to form apatite crystals after 21 d; and they were able to support cell growth and proliferation up to 14 d of culture. Besides, cellular proliferation was higher on the scaffolds coated with silk. These outcomes further demonstrate that the developed structures are suitable candidates to enhance bone tissue engineering.

Hydrogel, Electrospun and Composite Materials for Bone/Cartilage and Neural Tissue Engineering

Injuries of the bone/cartilage and central nervous system are still a serious socio-economic problem. They are an effect of diversified, difficult-to-access tissue structures as well as complex regeneration mechanisms. Currently, commercially available materials partially solve this problem, but they do not fulfill all of the bone/cartilage and neural tissue engineering requirements such as mechanical properties, biochemical cues or adequate biodegradation. There are still many things to do to provide complete restoration of injured tissues. Recent reports in bone/cartilage and neural tissue engineering give high hopes in designing scaffolds for complete tissue regeneration. This review thoroughly discusses the advantages and disadvantages of currently available commercial scaffolds and sheds new light on the designing of novel polymeric scaffolds composed of hydrogels, electrospun nanofibers, or hydrogels loaded with nano-additives.

Development and Utilization of Multifunctional Polymeric Scaffolds for the Regulation of Physical Cellular Microenvironments

Polymeric biomaterials exhibit excellent physicochemical characteristics as a scaffold for cell and tissue engineering applications. Chemical modification of the polymers has been the primary mode of functionalization to enhance biocompatibility and regulate cellular behaviors such as cell adhesion, proliferation, differentiation, and maturation. Due to the complexity of the in vivo cellular microenvironments, however, chemical functionalization alone is usually insufficient to develop functionally mature cells/tissues. Therefore, the multifunctional polymeric scaffolds that enable electrical, mechanical, and/or magnetic stimulation to the cells, have gained research interest in the past decade. Such multifunctional scaffolds are often combined with exogenous stimuli to further enhance the tissue and cell behaviors by dynamically controlling the microenvironments of the cells. Significantly improved cell proliferation and differentiation, as well as tissue functionalities, are frequently observed by applying extrinsic physical stimuli on functional polymeric scaffold systems. In this regard, the present paper discusses the current state-of-the-art functionalized polymeric scaffolds, with an emphasis on electrospun fibers, that modulate the physical cell niche to direct cellular behaviors and subsequent functional tissue development. We will also highlight the incorporation of the extrinsic stimuli to augment or activate the functionalized polymeric scaffold system to dynamically stimulate the cells.

Polylactide, Processed by a Foaming Method Using Compressed Freon R134a, for Tissue Engineering

Fabricating polymeric scaffolds using cost-effective manufacturing processes is still challenging. Gas foaming techniques using supercritical carbon dioxide (scCO2) have attracted attention for producing synthetic polymer matrices; however, the high-pressure requirements are often a technological barrier for its widespread use. Compressed 1,1,1,2-tetrafluoroethane, known as Freon R134a, offers advantages over CO2 in manufacturing processes in terms of lower pressure and temperature conditions and the use of low-cost equipment. Here, we report for the first time the use of Freon R134a for generating porous polymer matrices, specifically polylactide (PLA). PLA scaffolds processed with Freon R134a exhibited larger pore sizes, and total porosity, and appropriate mechanical properties compared with those achieved by scCO2 processing. PLGA scaffolds processed with Freon R134a were highly porous and showed a relatively fragile structure. Human mesenchymal stem cells (MSCs) attached to PLA scaffolds processed with Freon R134a, and their metabolic activity increased during culturing. In addition, MSCs displayed spread morphology on the PLA scaffolds processed with Freon R134a, with a well-organized actin cytoskeleton and a dense matrix of fibronectin fibrils. Functionalization of Freon R134a-processed PLA scaffolds with protein nanoparticles, used as bioactive factors, enhanced the scaffolds’ cytocompatibility. These findings indicate that gas foaming using compressed Freon R134a could represent a cost-effective and environmentally friendly fabrication technology to produce polymeric scaffolds for tissue engineering approaches.

Impact of statins on vascular scaffolds response in porcine carotid arteries

Surgical treatments of arterial occlusive disease with fully absorbable polymeric scaffolds, as a potential alternative to permanent metallic stents, are increasingly penetrating the clinical field. An addition part of the management of patients suffering from vascular diseases is the administration of statins. In this study, absorbable x-ray marked PLLA-based polymer scaffolds and permanent bare-metal stents (BMS) were implanted interventionally into both common carotid arteries (CCA) of 6 healthy female pigs via the left common iliac artery (8F-sheath). The pigs were administered dual antiplatelet drugs oral starting 3 days before the procedure until the end of the study. In Addition, the pigs received atorvastatin orally, beginning 5 days prior to surgery and lasting until the study ended. Stented CCA segments were explanted after 4 weeks, and processed for quantitative histomorphometry, and estimation of vascular inflammation and injury scores. Polymer scaffolds showed a decreased residual lumen area and higher stenosis after 4 weeks (6.41 ± 0.83 mm² and 40.52 ± 5.01%) as compared to the bare-metal reference stent (15.17 ± 0.896 mm² and 7.80 ± 0.88%). After 4 weeks, inflammation score were higher in the polymer group (1.30 ± 0.37) compared to the BMS group (0.42 ± 0.18). In contrast, the BMS showed a slightly elevated vascular injury score (0.85 ± 0.12), as compared to the polymer (0.60 ± 0.23) group. In this preclinical model, the new absorbable polymeric scaffolds showed similar technical feasibility and safety for vascular application as the permanent metal stents. Although no positive trends were observed with oral treatment with atorvastatin, further optimization with a dual-loaded coating is still reasonable. In addition, reduced strut thickness of the polymer scaffolds would have potential to positively impact tissue ingrowth between struts and should be considered in future work on stent design.

The application of iron oxide nanoparticles to control the release of minocycline for the treatment of glioblastoma

Background: The utilization of iron oxide nanoparticles (Fe3O4 NPs) to control minocycline release rates from poly(lactic-co-glycolic acid) scaffolds fabricated from an easy/economical technique is presented. Results/Methodology: A larger change in temperature and amount of minocycline released was observed for scaffolds with higher amounts of Fe3O4 NPs, demonstrating that nanoparticle concentration can control heat generation and minocycline release. Temperatures near a polymer’s glass transition temperature can result in the polymer’s chain becoming more mobile and thus increasing drug diffusion out of the scaffold. Elevated temperature and minocycline released from the scaffold can work synergistically to enhance glioblastoma cell death. Conclusion: This study suggests that Fe3O4 NPs are promising materials for controlling minocycline release from polymeric scaffolds by magnetic hyperthermia for the treatment of glioblastoma.

Glibenclamide Nanocrystal-Loaded Bioactive Polymeric Scaffolds for Skin Regeneration: In Vitro Characterization and Preclinical Evaluation

Skin restoration following full-thickness injury poses significant clinical challenges including inflammation and scarring. Medicated scaffolds formulated from natural bioactive polymers present an attractive platform for promoting wound healing. Glibenclamide was formulated in collagen/chitosan composite scaffolds to fulfill this aim. Glibenclamide was forged into nanocrystals with optimized colloidal properties (particle size of 352.2 nm, and polydispersity index of 0.29) using Kolliphor as a stabilizer to allow loading into the hydrophilic polymeric matrix. Scaffolds were prepared by the freeze drying method using different total polymer contents (3–6%) and collagen/chitosan ratios (0.25–2). A total polymer content of 3% at a collagen/chitosan ratio of 2:1 (SCGL3-2) was selected based on the results of in vitro characterization including the swelling index (1095.21), porosity (94.08%), mechanical strength, rate of degradation and in vitro drug release. SCGL3-2 was shown to be hemocompatible based on the results of protein binding, blood clotting and percentage hemolysis assays. In vitro cell culture studies on HSF cells demonstrated the biocompatibility of nanocrystals and SCGL3-2. In vivo studies on a rat model of a full-thickness wound presented rapid closure with enhanced histological and immunohistochemical parameters, revealing the success of the scaffold in reducing inflammation and promoting wound healing without scar formation. Hence, SCGL3-2 could be considered a potential dermal substitute for skin regeneration.