Karina Egle

Marine-derived natural polymers have attracted increasing interest as sustainable, high-value biomaterials for hydrogel development, owing to their biocompatibility, biodegradability, and tunable physicochemical properties. This study maps publication retrieval and patent trends related to marine-derived biopolymers and hydrogel cross-linking technologies between 2000 and 2024, based on keyword searches of four bibliographic databases combining “marine”, the biopolymer name and “cross-linking”, with or without a specific cross-linking type, and individually screened patent records. Retrieval counts increased overall in all four databases with all search categories reaching their highest counts in 2020–2024, and the number of patents rose sharply in 2020–2024. Over the study period, alginate and chitosan were the most frequently retrieved algae- and animal-derived biopolymers in each database, while patents were concentrated in health and medical applications, with collagen represented in the highest number of patents. Among the cross-linking type terms, “chemical” returned the most records in every database, and no records were retrieved for the enzymatic cross-linking of most algae-derived biopolymers. Fucoidan, hyaluronic acid and carrageenan occupied an intermediate position, whereas ulvan, laminarin, agarose and chondroitin sulfate were rarely retrieved and had limited or no patent data. The main rankings were consistent across all four databases and the individually screened patent records showed similar temporal and biopolymer patterns. Based on these data, marine-derived polymers were classified into three development tiers, and the barriers and opportunities for their further development are discussed.

The Doctoral Thesis is prepared as a thematically unified set of scientific publications, which includes four publications and a summary in Latvian and English. Platelet-rich fibrin (PRF) is an autologous material that can be obtained from human blood by centrifugation. The Doctoral Thesis has developed PRF-based matrices that can provide antimicrobial properties by adding drugs or their delivery systems and provide controlled delivery of bioactive molecules contained in PRF by evaluating different PRF carriers.

Promocijas darbs sagatavots kā tematiski vienota zinātnisko publikāciju kopa, kas ietver četras publikācijas, kā arī kopsavilkumu latviešu un angļu valodā. Ar trombocītiem bagātināts fibrīns (PRF) ir autologs materiāls, ko centrifugēšanas ceļā var iegūt no cilvēka asinīm. Promocijas darbā izstrādātas PRF balstītas matricas, kas var nodrošināt antimikrobiālas īpašības, pievienojot zāles vai to piegādes sistēmas, kā arī nodrošināt kontrolētu PRF sastāvā esošo bioaktīvo molekulu piegādi, izvērtējot dažādus PRF nesējus.

In recent decades, the potential of PRF has been extensively studied. The number of studies about PRF has increased three times since the year 2012, but the full spectrum of its fundamental properties, such as antimicrobial and anti-inflammatory activity, is not clearly described. In oral and maxillofacial surgery, PRF is described in alveolar ridge preservation, orthognathic surgery, cleft lip and palate surgery, maxillary sinus augmentation, and dental implant placement as demonstrating favorable results and its clinical advantages. The structural complexity, inhomogeneous nature, and clotting ability of PRF make its antimicrobial effect evaluation complicated. Nevertheless, most of the used antimicrobial testing methods are based on antibacterial agent diffusion ability in culture media. Because the oral and maxillofacial region is the most frequent area of PRF application, its antimicrobial activity evaluation also prevails in the oral microbiome. PRF’s biological potential is highly dependent on the specific preparation protocol and methodology used; it should be carefully prepared and kept under proper conditions to keep cellular content alive. PRF’s influence on living cells demonstrates a stimulating effect on bone regeneration, and an angiogenetic effect, and it provides anti-inflammatory activity. According to analyzed studies, PRF demonstrated success in oral and maxillofacial surgery in various methods of application. Antibacterial and anti-inflammatory properties were proven by antibacterial activity against different bacterial species, sustained growth factor, sustained release, and cell activity on the material application. Accurately and correctly prepared PRF can ensure antibacterial and anti-inflammatory properties, and it can be a beneficial clinical tool in oral and maxillofacial surgery.

The aim of this study was to investigate the change in clindamycin phosphate antibacterial properties against Gram-positive bacteria using the platelet-rich fibrin as a carrier matrix, and evaluate the changes in the antibiotic within the matrix. The antibacterial properties of CLP and its combination with PRF were tested in a microdilution test against reference cultures and clinical isolates of Staphylococcus aureus (S. aureus) or Staphylococcus epidermidis (S. epidermidis). Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) analysis was done to evaluate the changes in the PRF_CLP matrix. Release kinetics of CLP was defined with ultra-performance liquid chromatography (UPLC). According to FTIR data, the use of PRF as a carrier for CLP ensured the structural changes in the CLP toward a more active form of clindamycin. A significant decrease in minimal bactericidal concentration values (from 1000 µg/mL to 62 µg/mL) against reference cultures and clinical isolates of S. aureus and S. epidermidis was observed for the CLP and PRF samples if compared to pure CLP solution. In vitro cell viability tests showed that PRF and PRF with CLP have higher cell viability than 70% after 24 h and 48 h time points. This article indicates that CLP in combination with PRF showed higher antibacterial activity against S. aureus and S. epidermidis compared to pure CLP solution. This modified PRF could be used as a novel method to increase drug delivery and efficacy, and to reduce the risk of postoperative infection.

Our research focuses on combining the valuable properties of silk fibroin (SF) and calcium phosphate (CaP). SF is a natural protein with an easily modifiable structure; CaP is a mineral found in the human body. Most of the new age biocomposites lack interaction between organic/inorganic phase, thus SF/CaP composite could not only mimic the natural bone, but could also be used to make drug delivery systems as well, which can ensure both healing and regeneration. CaP was synthesized in situ in SF at different pH values, and then crosslinked with gelatin (G), horseradish peroxide (HRP), and hydrogen peroxide (H₂O₂). In addition, dexamethasone phosphate (DEX) was incorporated in the hydrogel and drug delivery kinetics was studied. Hydrogel made at pH 10.0 was found to have the highest gel fraction 110.24%, swelling degree 956.32%, and sustained drug delivery for 72 h. The highest cell viability was observed for the hydrogel, which contained brushite (pH 6)—512.43%.

The purpose of this review is to examine the latest literature on the use of autologous platelet-rich fibrin as a drug and growth factor carrier system in maxillofacial surgery. Autologous platelet-rich fibrin (PRF) is a unique system that combines properties such as biocompatibility and biodegradability, in addition to containing growth factors and peptides that provide tissue regeneration. This opens up new horizons for the use of all beneficial ingredients in the blood sample for biomedical purposes. By itself, PRF has an unstable effect on osteogenesis: therefore, advanced approaches, including the combination of PRF with materials or drugs, are of great interest in clinics. The main advantage of drug delivery systems is that by controlling drug release, high drug concentrations locally and fewer side effects within other tissue can be achieved. This is especially important in tissues with limited blood supply, such as bone tissue compared to soft tissue. The ability of PRF to degrade naturally is considered an advantage for its use as a “warehouse” of controlled drug release systems. We are focusing on this concentrate, as it is easy to use in manipulations and can be delivered directly to the surgical site. The target audience for this review are researchers and medical doctors who are involved in the development and research of PRFs further studies. Likewise, surgeons who use PRF in their work to treat patients and who advice patients to take the medicine orally.

Autologous platelet-rich fibrin (PRF) is derived from the blood and its use in the bone tissue engineering has emerged as an effective strategy for novel drug and growth factor delivery systems. Studies have approved that combined therapy with PRF ensures higher biological outcomes, but patients still undergo additional treatment with antibiotic drugs before, during, and even after the implantation of biomaterials with PRF. These systematically used drugs spread throughout the blood and lead not only to positive effects but may also induce adverse side effects on healthy tissues. Vancomycin hydrochloride (VANKA) is used to treat severe Staphylococcal infections but its absorption in the target tissue after oral administration is low; therefore, in this study, we have developed and analyzed two kinds of VANKA carriers—liposomes and microparticles in 3D PRF matrices. The adjustment, characterization, and analysis of VANKA carriers in 3D PRF scaffolds is carried out in terms of encapsulation efficiency, drug release kinetics and antibacterial activity; furthermore, we have studied the micro- and macrostructure of the scaffolds with microtomography.