Efficacy and safety of a new heterologous fibrin biopolymer on socket bone healing after tooth extraction: An experimental pre-clinical study.

AIM: To assess the efficacy of heterologous fibrin biopolymer (HFB) in promoting alveolar bone healing after tooth extraction in rats. MATERIALS AND METHODS: The upper right incisors of 48 Wistar rats were extracted. Toothless sockets were filled with HFB (HFBG, n = 24) or blood clot (BCG, n = 24). The tooth extraction sites were subjected to micro-computed tomography (micro-CT), histological, histomorphometric and immunohistochemical (for Runt-related transcription factor 2/Runx2 and tartrate-resistant acid phosphatase/TRAP) analyses on days 0, 7, 14 and 42 after extraction. RESULTS: Socket volume remained similar between days 0 and 14 (69 ± 5.4 mm3), except in the BCG on day 14, when it was 10% lower (p = .043). Although the number of Runx2+ osteoblasts was high and similar in both groups (34 × 102 cells/mm2), the HFBG showed lower inflammatory process and osteoclast activity than BCG at 7 days. On day 14, the number of Runx2+ osteoblasts remained high and similar to the previous period in both groups. However, osteoclast activity increased. This increase was 55% lower in the HFBG than BCG. In the BCG, the presence of an inflammatory process and larger and numerous osteoclasts on day 14 led to resorption of the alveolar bone ridge and newly formed bone. On day 42, numbers of Runx2+ osteoblast and TRAP+ osteoclasts decreased dramatically in both groups. Although the BCG exhibited a more mature cortical bone formation, it exhibited a higher socket reduction (28.3 ± 6.67%) and smaller bone volume (37 ± 5.8 mm3) compared with HFBG (socket reduction of 14.8 ± 7.14% and total bone volume of 46 ± 5.4 mm3). CONCLUSIONS: HFB effectively suppresses osteoclast activity and reduces alveolar bone resorption compared with blood clot, thus preventing three-dimensional bone loss, particularly during the early healing period. HFB emerges as a promising biopharmaceutical material for enhancing healing processes after tooth extraction.

Prospects of Using Chitosan-Based Biopolymers in the Treatment of Peripheral Nerve Injuries.

Peripheral nerve injuries are common neurological disorders, and the available treatment options, such as conservative management and surgical repair, often yield limited results. However, there is growing interest in the potential of using chitosan-based biopolymers as a novel therapeutic approach to treating these injuries. Chitosan-based biopolymers possess unique characteristics, including biocompatibility, biodegradability, and the ability to stimulate cell proliferation, making them highly suitable for repairing nerve defects and promoting nerve regeneration and functional recovery. Furthermore, these biopolymers can be utilized in drug delivery systems to control the release of therapeutic agents and facilitate the growth of nerve cells. This comprehensive review focuses on the latest advancements in utilizing chitosan-based biopolymers for peripheral nerve regeneration. By harnessing the potential of chitosan-based biopolymers, we can pave the way for innovative treatment strategies that significantly improve the outcomes of peripheral nerve injury repair, offering renewed hope and better prospects for patients in need.

Overview of Antimicrobial Biodegradable Polyester-Based Formulations.

As the clinical complications induced by microbial infections are known to have life-threatening side effects, conventional anti-infective therapy is necessary, but not sufficient to overcome these issues. Some of their limitations are connected to drug-related inefficiency or resistance and pathogen-related adaptive modifications. Therefore, there is an urgent need for advanced antimicrobials and antimicrobial devices. A challenging, yet successful route has been the development of new biostatic or biocide agents and biomaterials by considering the indisputable advantages of biopolymers. Polymers are attractive materials due to their physical and chemical properties, such as compositional and structural versatility, tunable reactivity, solubility and degradability, and mechanical and chemical tunability, together with their intrinsic biocompatibility and bioactivity, thus enabling the fabrication of effective pharmacologically active antimicrobial formulations. Besides representing protective or potentiating carriers for conventional drugs, biopolymers possess an impressive ability for conjugation or functionalization. These aspects are key for avoiding malicious side effects or providing targeted and triggered drug delivery (specific and selective cellular targeting), and generally to define their pharmacological efficacy. Moreover, biopolymers can be processed in different forms (particles, fibers, films, membranes, or scaffolds), which prove excellent candidates for modern anti-infective applications. This review contains an overview of antimicrobial polyester-based formulations, centered around the effect of the dimensionality over the properties of the material and the effect of the production route or post-processing actions.

Antibody-Biopolymer Conjugates in Oncology: A Review.

Cancer is one of the most prevalent diseases and affects a large proportion of the population worldwide. Conventional treatments in the management include chemotherapy, radiotherapy, and surgery. Although being well-accepted, they have many lacunas in the form of severe side effect resulting from lack of targeted delivery. Antibody biopolymer conjugates are a novel method which is an add-on to older methods of immunization. It is used in various diseases and disorders. It ensures the targeted delivery of molecules to increase its efficacy and reduce unwanted effects of the molecule/drug to normal cells. It shows miraculous results in the treatment and management of several cancers even in advanced stages. Herein, we present the chemistry between biopolymer and antibody, their effects on cancer as well as the basic differences between antibody-drug conjugates and antibody-biopolymer conjugates.

EFFECTIVENESS OF THE APPLICATION OF THE DEVELOPED BIOPOLYMER FIBROUS MATRIX WITH CENOBONE® BIOGEL FOR THE RECONSTRUCTION OF BONE TISSUE DEFECTS OF THE JAWS.

The aim of the research was to study the framework ability of the fibrous non-woven PCL matrices we've created during the restoration of bone tissue.There were performed some spectroscopic, histological and immunohistochemical, radiological and clinical analyses of the effectiveness of microfibrous non-woven PCL polycaprolactone matrices developed by us, in the work. The obtained results of morphological studies of bone tissue in the experiment of the implantation of a fibrous matrix indicated an increase in reparative osteogenesis in the form of an increase in osteoid areas up to 34.38% (p<0.05) at an early period. The analysis of clinical data showed the effectiveness of the frame developed by us, which was confirmed by the absence of pronounced compaction of bone tissue in group III, in contrast to group II, where, on the contrary, the use of granulate based on hydroxyapatite and tricalcium phosphate has led to a significant increase in density indices of 974.53+19.74 HU p<0.05, which did not exceed 36.8% of indices of the group III 615.17+24.53 HU p<0.05.The matrix material developed by us is not only a means of delivering some other substances and materials into the damaged area, but also serves as a kind of framework for the restoration of bone tissue.

Borrowing the Features of Biopolymers for Emerging Wound Healing Dressings: A Review.

Wound dressing design is a dynamic and rapidly growing field of the medical wound-care market worldwide. Advances in technology have resulted in the development of a wide range of wound dressings that treat different types of wounds by targeting the four phases of healing. The ideal wound dressing should perform rapid healing; preserve the body's water content; be oxygen permeable, non-adherent on the wound and hypoallergenic; and provide a barrier against external contaminants-at a reasonable cost and with minimal inconvenience to the patient. Therefore, choosing the best dressing should be based on what the wound needs and what the dressing does to achieve complete regeneration and restoration of the skin's structure and function. Biopolymers, such as alginate (ALG), chitosan (Cs), collagen (Col), hyaluronic acid (HA) and silk fibroin (SF), are extensively used in wound management due to their biocompatibility, biodegradability and similarity to macromolecules recognized by the human body. However, most of the formulations based on biopolymers still show various issues; thus, strategies to combine them with molecular biology approaches represent the future of wound healing. Therefore, this article provides an overview of biopolymers' roles in wound physiology as a perspective on the development of a new generation of enhanced, naturally inspired, smart wound dressings based on blood products, stem cells and growth factors.

Bioaerogels: Promising Nanostructured Materials in Fluid Management, Healing and Regeneration of Wounds.

Wounds affect one's quality of life and should be managed on a patient-specific approach, based on the particular healing phase and wound condition. During wound healing, exudate is produced as a natural response towards healing. However, excessive production can be detrimental, representing a challenge for wound management. The design and development of new healing devices and therapeutics with improved performance is a constant demand from the healthcare services. Aerogels can combine high porosity and low density with the adequate fluid interaction and drug loading capacity, to establish hemostasis and promote the healing and regeneration of exudative and chronic wounds. Bio-based aerogels, i.e., those produced from natural polymers, are particularly attractive since they encompass their intrinsic chemical properties and the physical features of their nanostructure. In this work, the emerging research on aerogels for wound treatment is reviewed for the first time. The current scenario and the opportunities provided by aerogels in the form of films, membranes and particles are identified to face current unmet demands in fluid managing and wound healing and regeneration.

Chitosan and gelatin biopolymer supplemented with mesenchymal stem cells (Velgraft®) enhanced wound healing in goats (Capra hircus): Involvement of VEGF, TGF and CD31.

AIM: Cell-based therapy has emerged as promising strategy for chronic and impaired wounds treatment. Current research is focused on developing biomaterial systems that act as a niche for mesenchymal stem cells (MSCs) to promote wound healing through paracrine molecular cascading. This study was aimed to evaluate the wound healing potential of Velgraft, a ready-to-use biodegradable artificial skin substitute, on excision wound in goats. MATERIALS AND METHODS: Twelve male goats were randomized divided in to three groups of four animals each. After infliction of surgical wound, Velgraft and Soframycin were applied on wounds of the animals of Groups II and III while Group I (sham operated) served as control. Wound diameters were measured at pre-defined time-points for determination of progressive wound healing up to 28 days. Skin sections were stained using Hematoxylin and eosin (H&E) for examining the histoarchitectural changes, Masson trichome staining for ascertaining collagen synthesis and immunohistochemistry for expression of CD31, VEGF and TGF-ß1 proteins to determine post-treatment angiogenesis in the inflicted wounds. RESULTS: Velgraft application appreciably enhanced wound closure by day 21 which was confirmed through restoration of the normal skin architecture as evident based on histopathological examination and characterized by complete regeneration of epidermal layers, collagen fibers, blood capillaries and hair follicular formation. Stimulation of angiogenesis markers was also observed at different time-points post-Velgraft application; which is suggestive of the improved angiogenesis and vasculogenesis. CONCLUSION: Velgraft facilitates wound healing by augmenting early wound closure, enhancing collagen synthesis and deposition, trichosis development and promoting revascularization and epidermal layers restoration.

Tooth-Supporting Hard Tissue Regeneration Using Biopolymeric Material Fabrication Strategies.

The mineralized tissues (alveolar bone and cementum) are the major components of periodontal tissues and play a critical role to anchor periodontal ligament (PDL) to tooth-root surfaces. The integrated multiple tissues could generate biological or physiological responses to transmitted biomechanical forces by mastication or occlusion. However, due to periodontitis or traumatic injuries, affect destruction or progressive damage of periodontal hard tissues including PDL could be affected and consequently lead to tooth loss. Conventional tissue engineering approaches have been developed to regenerate or repair periodontium but, engineered periodontal tissue formation is still challenging because there are still limitations to control spatial compartmentalization for individual tissues and provide optimal 3D constructs for tooth-supporting tissue regeneration and maturation. Here, we present the recently developed strategies to induce osteogenesis and cementogenesis by the fabrication of 3D architectures or the chemical modifications of biopolymeric materials. These techniques in tooth-supporting hard tissue engineering are highly promising to promote the periodontal regeneration and advance the interfacial tissue formation for tissue integrations of PDL fibrous connective tissue bundles (alveolar bone-to-PDL or PDL-to-cementum) for functioning restorations of the periodontal complex.

Atom Transfer Radical Polymerization for Biorelated Hybrid Materials.

Proteins, nucleic acids, lipid vesicles, and carbohydrates are the major classes of biomacromolecules that function to sustain life. Biology also uses post-translation modification to increase the diversity and functionality of these materials, which has inspired attaching various other types of polymers to biomacromolecules. These polymers can be naturally (carbohydrates and biomimetic polymers) or synthetically derived and have unique properties with tunable architectures. Polymers are either grafted-to or grown-from the biomacromolecule's surface, and characteristics including polymer molar mass, grafting density, and degree of branching can be controlled by changing reaction stoichiometries. The resultant conjugated products display a chimerism of properties such as polymer-induced enhancement in stability with maintained bioactivity, and while polymers are most often conjugated to proteins, they are starting to be attached to nucleic acids and lipid membranes (cells) as well. The fundamental studies with protein-polymer conjugates have improved our synthetic approaches, characterization techniques, and understanding of structure-function relationships that will lay the groundwork for creating new conjugated biomacromolecular products which could lead to breakthroughs in genetic and tissue engineering.

Magnetic Composite Scaffolds for Potential Applications in Radiochemotherapy of Malignant Bone Tumors.

Background and objectives: Cancer is the second leading cause of death globally, an alarming but expected increase. In comparison to other types of cancer, malignant bone tumors are unusual and their treatment is a real challenge. This paper's main purpose is the study of the potential application of composite scaffolds based on biopolymers and calcium phosphates with the inclusion of magnetic nanoparticles in combination therapy for malignant bone tumors. Materials and Methods: The first step was to investigate if X-rays could modify the scaffolds' properties. In vitro degradation of the scaffolds exposed to X-rays was analyzed, as well as their interaction with phosphate buffer solutions and cells. The second step was to load an anti-tumoral drug (doxorubicin) and to study in vitro drug release and its interaction with cells. The chemical structure of the scaffolds and their morphology were studied. Results: Analyses showed that X-ray irradiation did not influence the scaffolds' features. Doxorubicin release was gradual and its interaction with cells showed cytotoxic effects on cells after 72 h of direct contact. Conclusions: The obtained scaffolds could be considered in further studies regarding combination therapy for malignant bone tumors.

Biopolymers: Applications in wound healing and skin tissue engineering.

Wound is a growing healthcare challenge affecting several million worldwide. Lifestyle disorders such as diabetes increases the risk of wound complications. Effective management of wound is often difficult due to the complexity in the healing process. Addition to the conventional wound care practices, the bioactive polymers are gaining increased importance in wound care. Biopolymers are naturally occurring biomolecules synthesized by microbes, plants and animals with highest degree of biocompatibility. The bioactive properties such as antimicrobial, immune-modulatory, cell proliferative and angiogenic of the polymers create a microenvironment favorable for the healing process. The versatile properties of the biopolymers such as cellulose, alginate, hyaluronic acid, collagen, chitosan etc have been exploited in the current wound care market. With the technological advances in material science, regenerative medicine, nanotechnology, and bioengineering; the functional and structural characteristics of biopolymers can be improved to suit the current wound care demands such as tissue repair, restoration of lost tissue integrity and scarless healing. In this review we highlight on the sources, mechanism of action and bioengineering approaches adapted for commercial exploitation.

Semi-IPN- and IPN-Based Hydrogels.

Semi-interpenetrating polymer networks (semi-IPNs) and interpenetrating polymeric networks (IPNs) have emerged as innovative materials for biomedical and pharmaceutical applications. The interest in these structures is due to the possibility of combining the favorable properties of each polymeric component of the IPNs or semi-IPNs leading to a new system with properties that often differ from those of the two single components. In this respect, polysaccharides represent an opportunity in this field, combining a general biocompatibility and a good availability. Moreover, the functional groups along the polymer chains allow chemical derivatization, widening the possibilities in semi-IPNs and IPNs building up. At the same time, materials based on proteins are often used in this field, due to their similarity to the materials present in the human body. All these overall properties allow tailoring new materials, thus designing desired properties and preparing new hydrogels useful in the biomedical field. In the present chapter, we chose to describe systems prepared starting from the most important and studied hydrogel-forming polysaccharides: alginate, hyaluronic acid, chitosan, dextran, gellan, and scleroglucan. Besides, systems based on proteins, such as gelatin, collagen, and elastin, are also described. With this chapter, we aim describing the routes already traveled in this field, depicting the state of the art and hoping to raise interest in designing new promising strategies useful in biomedical and pharmaceutical applications.

Chitosan magnetic nanoparticles for drug delivery systems.

The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

Synthesis, Characterization and Biological Activities of Biopolymeric Schiff Bases Prepared with Chitosan and Salicylaldehydes and Their Pd(II) and Pt(II) Complexes.

In an attempt to enhance chitosan biological activities, biopolymeric Schiff bases of chitosan and different salicylaldehydes and their palladium(II) and platinum(II) complexes were synthesized and tested. The chemical structures of these derivatives were characterized using ¹H-NMR, FTIR spectroscopy and XPRD. Thermal analysis was done through TGA/DTG-DTA. Electronic absorption spectra and surface morphologies were analyzed by SEM-EDAX. Chitosan and its derivatives were evaluated for their in vitro antimicrobial activity against two common bacterial and fungal plant pathogens Pseudomonas syringae pv. tomato and Fusarium graminearum, respectively, and for their antitumor activity against a human breast cancer cell line (MCF-7). It was found that, compared to the nonmodified chitosan, chitosan modified with Schiff bases and their complexes was highly toxic against the MCF-7 cell line and had antibacterial effects against P. syringea. However, the modified chitosan derivatives had less pronounced antifungal effects against F. graminearum compared to the nonmodified chitosan, suggesting different modes of action.

Chitin and chitosan: biopolymers for wound management.

Chitin and chitosan are biopolymers with excellent bioactive properties, such as biodegradability, non-toxicity, biocompatibility, haemostatic activity and antimicrobial activity. A wide variety of biomedical applications for chitin and chitin derivatives have been reported, including wound-healing applications. They are reported to promote rapid dermal regeneration and accelerate wound healing. A number of dressing materials based on chitin and chitosan have been developed for the treatment of wounds. Chitin and chitosan with beneficial intrinsic properties and high potential for wound healing are attractive biopolymers for wound management. This review presents an overview of properties, biomedical applications and the role of these biopolymers in wound care.

Specific Uptake of Lipid-Antibody-Functionalized LbL Microcarriers by Cells.

The modular construction of Layer-by-Layer biopolymer microcarriers facilitates a highly specific design of drug delivery systems. A supported lipid bilayer (SLB) contributes to biocompatibility and protection of sensitive active agents. The addition of a lipid anchor equipped with PEG (shielding from opsonins) and biotin (attachment of exchangeable outer functional molecules) enhances the microcarrier functionality even more. However, a homogeneously assembled supported lipid bilayer is a prerequisite for a specific binding of functional components. Our investigations show that a tightly packed SLB improves the efficiency of functional components attached to the microcarrier's surface, as illustrated with specific antibodies in cellular application. Only a low quantity of antibodies is needed to obtain improved cellular uptake rates independent from cell type as compared to an antibody-functionalized loosely packed lipid bilayer or directly assembled antibody onto the multilayer. A fast disassembly of the lipid bilayer within endolysosomes exposing the underlying drug delivering multilayer structure demonstrates the suitability of LbL-microcarriers as a multifunctional drug delivery system.

Biopolymeric agents for skin wrinkle treatment.

Skin aging is caused by several factors capable of deteriorating dermal matrix and is visibly noticed in skin color and skin contour deformities. In addition to the prevention of skin aging by application of antioxidants and sunscreens, treatment of skin wrinkles with those of dermal fillers is also recommended. Dermal filler products with enhanced injectability and longer duration are being developed continuously. Biodegradable polymers such as skin elastic fibers and dermal matrix mimetic used for treatment of skin wrinkle are summarized in this article. Additionally, the importance of amino acids, enzymes, and proteins in aesthetic of skin is addressed. Thus, elective agents are proposed for the dermatologists, cosmetic formulators, and the individuals facing skin aging problems. The candidate natural peptides from marine sources are additionally presented for widening the choice of actives application for treating aging.

Experimental use of a cellulosic biopolymer as a new material for suburethral sling in the treatment of stress urinary incontinence.

PURPOSE: To analyze the interaction between the cellulose exopolysaccharide (CEC) and urethral tissue when used as a pubovaginal sling. MATERIALS AND METHODS: Forty Wistar rats were divided into four groups. In groups A and B the cellulose exopolysaccharide (CEC) was implanted around the urethral tissue (bladder neck below the upper margin) and the rats were sacrificed at 30 and 90 days. Similar procedure was used in groups C and D using a polypropylene mesh. After sacrifice bladder and urethra were sent for histological analysis. The histological parameters (inflammatory reaction) by evaluated by quantitative analysis. For collagen deposition analysis it was used stereological method. RESULTS: The cellulose exopolysaccharide (CEC) was inert and well preserved at the implanted region at the time of examination. Morphologic alterations were not found at the CEC implant but some reactions of foreign body type were observed at the adjacent structures. In some areas a process of neovascular formation was observed. Stereological analysis at the suburethral area showed a significant difference in collagen presence in favor of CEC. CONCLUSIONS: The CEC implant showed adequate results when used as a suburethral sling with good integration to the host tissue, preserving its architecture.

Bacterial Cellulose Applied in Wound Dressing Materials: Production and Functional Modification - A Review.

In recent years, the development of new type wound dressings has gradually attracted more attention. Bacterial cellulose (BC) is a natural polymer material with various unique properties, such as ultrafine 3D nanonetwork structure, high water retention capacity, and biocompatibility. These properties allow BC to be used independently or in combination with different components (such as biopolymers and nanoparticles) to achieve diverse effects. This means that BC has great potential as a wound dressing. However, systematic summaries for the production and commercial application of BC-based wound dressings are still lacking. Therefore, this review provides a detailed introduction to the production fermentation process of BC, including various production strains and their biosynthetic mechanisms. Subsequently, with regard to the functional deficiencies of bacterial cellulose as a wound dressing, recent research progress in this area is enumerated. Finally, prospects are discussed for the low-cost production and high-value-added product development of BC-based wound dressings.