Generation of Pearl/Calcium Phosphate Composite Particles and Their Integration into Porous Chitosan Scaffolds for Bone Regeneration.

Bone tissue engineering using osteoconductive scaffolds holds promise for regeneration, with pearl powder gaining interest for its bioactive qualities. This study used freeze drying to create chitosan (CS) scaffolds with pearl/calcium phosphate (p/CaP) powders, mimicking bone tissue structurally and compositionally. Characterization included scanning electron microscopy (SEM) and mechanical testing. X-ray diffraction (XRD) Fourier-transform infrared-photoacoustic photo-acoustic sampling (FTIR-PAS), and FTIR- attenuated total reflectance (FTIR-ATR) were used to characterize p/CaP. In vitro tests covered degradation, cell activity, and SEM analysis. The scaffolds showed notable compressive strength and modulus enhancements with increasing p/CaP content. Porosity, ranging from 60% to 90%, decreased significantly at higher pearl/CaP ratios. Optimal cell proliferation and differentiation were observed with scaffolds containing up to 30 wt.% p/CaP, with 30 wt.% pearl powder and 30 wt.% p/CaP yielding the best results. In conclusion, pearl/calcium phosphate chitosan (p/CaP_CS) composite scaffolds emerged as promising biomaterials for bone tissue engineering, combining structural mimicry and favourable biological responses.

Endothelialization of Whey Protein Isolate-Based Scaffolds for Tissue Regeneration.

BACKGROUND: Whey protein isolate (WPI) is a by-product from the dairy industry, whose main component is ß-lactoglobulin. Upon heating, WPI forms a hydrogel which can both support controlled drug delivery and enhance the proliferation and osteogenic differentiation of bone-forming cells. This study makes a novel contribution by evaluating the ability of WPI hydrogels to support the growth of endothelial cells, which are essential for vascularization, which in turn is a pre-requisite for bone regeneration. METHODS: In this study, the proliferation and antioxidant levels in human umbilical vascular endothelial cells (HUVECs) cultured with WPI supplementation were evaluated using real-time cell analysis and flow cytometry. Further, the attachment and growth of HUVECs seeded on WPI-based hydrogels with different concentrations of WPI (15%, 20%, 30%, 40%) were investigated. RESULTS: Supplementation with WPI did not affect the viability or proliferation of HUVECs monitored with real-time cell analysis. At the highest used concentration of WPI (500 µg/mL), a slight induction of ROS production in HUVECs was detected as compared with control samples, but it was not accompanied by alterations in cellular thiol levels. Regarding WPI-based hydrogels, HUVEC adhered and spread on all samples, showing good metabolic activity. Notably, cell number was highest on samples containing 20% and 30% WPI. CONCLUSIONS: The demonstration of the good compatibility of WPI hydrogels with endothelial cells in these experiments is an important step towards promoting the vascularization of hydrogels upon implantation in vivo, which is expected to improve implant outcomes in the future.

Whey Protein Isolate/Calcium Silicate Hydrogels for Bone Tissue Engineering Applications-Preliminary In Vitro Evaluation.

Whey protein isolate (WPI) hydrogels are attractive biomaterials for application in bone repair and regeneration. However, their main limitation is low mechanical strength. Therefore, to improve these properties, the incorporation of ceramic phases into hydrogel matrices is currently being performed. In this study, novel whey protein isolate/calcium silicate (WPI/CaSiO3) hydrogel biomaterials were prepared with varying concentrations of a ceramic phase (CaSiO3). The aim of this study was to investigate the effect of the introduction of CaSiO3 to a WPI hydrogel matrix on its physicochemical, mechanical, and biological properties. Our Fourier Transform Infrared Spectroscopy results showed that CaSiO3 was successfully incorporated into the WPI hydrogel matrix to create composite biomaterials. Swelling tests indicated that the addition of 5% (w/v) CaSiO3 caused greater swelling compared to biomaterials without CaSiO3 and ultimate compressive strength and strain at break. Cell culture experiments demonstrated that WPI hydrogel biomaterials enriched with CaSiO3 demonstrated superior cytocompatibility in vitro compared to the control hydrogel biomaterials without CaSiO3. Thus, this study revealed that the addition of CaSiO3 to WPI-based hydrogel biomaterials renders them more promising for bone tissue engineering applications.

The Effect of Chitosan on Physicochemical Properties of Whey Protein Isolate Scaffolds for Tissue Engineering Applications.

New scaffolds, based on whey protein isolate (WPI) and chitosan (CS), have been proposed and investigated as possible materials for use in osteochondral tissue repair. Two types of WPI-based hydrogels modified by CS were prepared: CS powder was incorporated into WPI in either dissolved or suspended powder form. The optimal chemical composition of the resulting WPI/CS hydrogels was chosen based on the morphology, structural properties, chemical stability, swelling ratio, wettability, mechanical properties, bioactivity, and cytotoxicity evaluation. The hydrogels with CS incorporated in powder form exhibited superior mechanical properties and higher porosity, whereas those with CS incorporated after dissolution showed enhanced wettability, which decreased with increasing CS content. The introduction of CS powder into the WPI matrix promoted apatite formation, as confirmed by energy dispersive spectroscopy (EDS) and Fourier transform infrared spectroscopy (FTIR) analyses. In vitro cytotoxicity results confirmed the cytocompatibility of CS powder modified WPI hydrogels, suggesting their suitability as cell scaffolds. These findings demonstrate the promising potential of WPI/CS scaffolds for osteochondral tissue repair.

Designing of gradient scaffolds and their applications in tissue regeneration.

Gradient scaffolds are isotropic/anisotropic three-dimensional structures with gradual transitions in geometry, density, porosity, stiffness, etc., that mimic the biological extracellular matrix. The gradient structures in biological tissues play a major role in various functional and metabolic activities in the body. The designing of gradients in the scaffold can overcome the current challenges in the clinic compared to conventional scaffolds by exhibiting excellent penetration capacity for nutrients & cells, increased cellular adhesion, cell viability & differentiation, improved mechanical stability, and biocompatibility. In this review, the recent advancements in designing gradient scaffolds with desired biomimetic properties, and their implication in tissue regeneration applications have been briefly explained. Furthermore, the gradients in native tissues such as bone, cartilage, neuron, cardiovascular, skin and their specific utility in tissue regeneration have been discussed in detail. The insights from such advances using gradient-based scaffolds can widen the horizon for using gradient biomaterials in tissue regeneration applications.

The Enrichment of Whey Protein Isolate Hydrogels with Poly-γ-Glutamic Acid Promotes the Proliferation and Osteogenic Differentiation of Preosteoblasts.

Osseous disease accounts for over half of chronic pathologies, but there is a limited supply of autografts, the gold standard; hence, there is a demand for new synthetic biomaterials. Herein, we present the use of a promising, new dairy-derived biomaterial: whey protein isolate (WPI) in the form of hydrogels, modified with the addition of different concentrations of the biotechnologically produced protein-like polymeric substance poly-γ-glutamic acid (γ-PGA) as a potential scaffold for tissue regeneration. Raman spectroscopic analysis demonstrated the successful creation of WPI-γ-PGA hydrogels. A cytotoxicity assessment using preosteoblastic cells demonstrated that the hydrogels were noncytotoxic and supported cell proliferation from day 3 to 14. All γ-PGA-containing scaffold compositions strongly promoted cell attachment and the formation of dense interconnected cell layers. Cell viability was significantly increased on γ-PGA-containing scaffolds on day 14 compared to WPI control scaffolds. Significantly, the cells showed markers of osteogenic differentiation; they synthesised increasing amounts of collagen over time, and cells showed significantly enhanced alkaline phosphatase activity at day 7 and higher levels of calcium for matrix mineralization at days 14 and 21 on the γ-PGA-containing scaffolds. These results demonstrated the potential of WPI-γ-PGA hydrogels as scaffolds for bone regeneration.

Could Curdlan/Whey Protein Isolate/Hydroxyapatite Biomaterials Be Considered as Promising Bone Scaffolds?-Fabrication, Characterization, and Evaluation of Cytocompatibility towards Osteoblast Cells In Vitro.

The number of bone fractures and cracks requiring surgical interventions increases every year; hence, there is a huge need to develop new potential bone scaffolds for bone regeneration. The goal of this study was to gain knowledge about the basic properties of novel curdlan/whey protein isolate/hydroxyapatite biomaterials in the context of their use in bone tissue engineering. The purpose of this research was also to determine whether the concentration of whey protein isolate in scaffolds has an influence on their properties. Thus, two biomaterials differing in the concentration of whey protein isolate (i.e., 25 wt.% and 35 wt.%; hereafter called Cur_WPI25_HAp and Cur_WPI35_HAp, respectively) were fabricated and subjected to evaluation of porosity, mechanical properties, swelling ability, protein release capacity, enzymatic biodegradability, bioactivity, and cytocompatibility towards osteoblasts in vitro. It was found that both biomaterials fulfilled a number of requirements for bone scaffolds, as they demonstrated limited swelling and the ability to undergo controllable enzymatic biodegradation, to form apatite layers on their surfaces and to support the viability, growth, proliferation, and differentiation of osteoblasts. On the other hand, the biomaterials were characterized by low open porosity, which may hinder the penetration of cells though their structure. Moreover, they had low mechanical properties compared to natural bone, which limits their use to filling of bone defects in non-load bearing implantation areas, e.g., in the craniofacial area, but then they will be additionally supported by application of mechanically strong materials such as titanium plates. Thus, this preliminary in vitro research indicates that biomaterials composed of curdlan, whey protein isolate, and hydroxyapatite seem promising for bone tissue engineering applications, but their porosity and mechanical properties should be improved. This will be the subject of our further work.

Biomimetic biphasic curdlan-based scaffold for osteochondral tissue engineering applications - Characterization and preliminary evaluation of mesenchymal stem cell response in vitro.

Osteochondral defects remain a huge problem in medicine today. Biomimetic bi- or multi-phasic scaffolds constitute a very promising alternative to osteochondral autografts and allografts. In this study, a new curdlan-based scaffold was designed for osteochondral tissue engineering applications. To achieve biomimetic properties, it was enriched with a protein component - whey protein isolate as well as a ceramic ingredient - hydroxyapatite granules. The scaffold was fabricated via a simple and cost-efficient method, which represents a significant advantage. Importantly, this technique allowed generation of a scaffold with two distinct, but integrated phases. Scanning electron microcopy and optical profilometry observations demonstrated that phases of biomaterial possessed different structural properties. The top layer of the biomaterial (mimicking the cartilage) was smoother than the bottom one (mimicking the subchondral bone), which is beneficial from a biological point of view because unlike bone, cartilage is a smooth tissue. Moreover, mechanical testing showed that the top layer of the biomaterial had mechanical properties close to those of natural cartilage. Although the mechanical properties of the bottom layer of scaffold were lower than those of the subchondral bone, it was still higher than in many analogous systems. Most importantly, cell culture experiments indicated that the biomaterial possessed high cytocompatibility towards adipose tissue-derived mesenchymal stem cells and bone marrow-derived mesenchymal stem cells in vitro. Both phases of the scaffold enhanced cell adhesion, proliferation, and chondrogenic differentiation of stem cells (revealing its chondroinductive properties in vitro) as well as osteogenic differentiation of these cells (revealing its osteoinductive properties in vitro). Given all features of the novel curdlan-based scaffold, it is worth noting that it may be considered as promising candidate for osteochondral tissue engineering applications.

WPI Hydrogels with a Prolonged Drug-Release Profile for Antimicrobial Therapy.

Infectious sequelae caused by surgery are a significant problem in modern medicine due to their reduction of therapeutic effectiveness and the patients' quality of life.Recently, new methods of local antimicrobial prophylaxis of postoperative sequelae have been actively developed. They allow high local concentrations of drugs to be achieved, increasing the antibiotic therapy's effectiveness while reducing its side effects. We have developed and characterized antimicrobial hydrogels based on an inexpensive and biocompatible natural substance from the dairy industry-whey protein isolate-as matrices for drug delivery. The release of cefazolin from the pores of hydrogel structures directly depends on the amount of the loaded drug and occurs in a prolonged manner for three days. Simultaneously with the antibiotic release, hydrogel swelling and partial degradation occurs. The WPI hydrogels absorb solvent, doubling in size in three days and retaining cefazolin throughout the duration of the experiment. The antimicrobial activity of cefazolin-loaded WPI hydrogels against Staphylococcus aureus growth is prolonged in comparison to that of the free cefazolin. The overall cytotoxic effect of cefazolin-containing WPI hydrogels is lower than that of free antibiotics. Thus, our work shows that antimicrobial WPI hydrogels are suitable candidates for local antibiotic therapy of infectious surgical sequelae.

Newly crosslinked chitosan- and chitosan-pectin-based hydrogels with high antioxidant and potential anticancer activity.

Monoaldehydes, due to natural origin and therapeutic activity, have attracted great attention for their ability to crosslink chitosan hydrogels for biomedical applications. However, most studies have focused on single-component hydrogels. In this work, chitosan-based hydrogels, crosslinked for the first time with 2,3,4-trihydroxybenzaldehyde (THBA), were modified with pectin (PC), bioactive glass (BG), and rosmarinic acid (RA). All of these were not only involved in the crosslinking, but also modulated properties or imparted completely new ones. THBA functioned as a crosslinker, resulting in improved mechanical properties, high swelling capacity and delayed degradation and also imparted high antioxidant activity and antiproliferative effect on cancer cells without cytotoxicity for normal cells. Hydrogels containing PC showed enhanced mechanical strength, while the combination with BG gave improved stability in PBS. All hydrogels modified with BG exhibited the ability to mineralise in SBF. The addition of RA enhanced antioxidant and anticancer activities and promoting the mineralisation process.

Freeze-Dried Curdlan/Whey Protein Isolate-Based Biomaterial as Promising Scaffold for Matrix-Associated Autologous Chondrocyte Transplantation-A Pilot In-Vitro Study.

The purpose of this pilot study was to establish whether a novel freeze-dried curdlan/whey protein isolate-based biomaterial may be taken into consideration as a potential scaffold for matrix-associated autologous chondrocyte transplantation. For this reason, this biomaterial was initially characterized by the visualization of its micro- and macrostructures as well as evaluation of its mechanical stability, and its ability to undergo enzymatic degradation in vitro. Subsequently, the cytocompatibility of the biomaterial towards human chondrocytes (isolated from an orthopaedic patient) was assessed. It was demonstrated that the novel freeze-dried curdlan/whey protein isolate-based biomaterial possessed a porous structure and a Young's modulus close to those of the superficial and middle zones of cartilage. It also exhibited controllable degradability in collagenase II solution over nine weeks. Most importantly, this biomaterial supported the viability and proliferation of human chondrocytes, which maintained their characteristic phenotype. Moreover, quantitative reverse transcription PCR analysis and confocal microscope observations revealed that the biomaterial may protect chondrocytes from dedifferentiation towards fibroblast-like cells during 12-day culture. Thus, in conclusion, this pilot study demonstrated that novel freeze-dried curdlan/whey protein isolate-based biomaterial may be considered as a potential scaffold for matrix-associated autologous chondrocyte transplantation.

The influence of Ca/Mg ratio on autogelation of hydrogel biomaterials with bioceramic compounds.

Hydrogels, which are versatile three-dimensional structures containing polymers and water, are very attractive for use in biomedical fields, but they suffer from rather weak mechanical properties. In this regard, biocompatible particles can be used to enhance their mechanical properties. The possibility of loading such particles with drugs (e.g. enzymes) makes them a particularly useful component in hydrogels. In this study, micro/nanoparticles containing various ratios of Ca2+/Mg2+ with sizes ranging from 1 to 8 µm were prepared and mixed with gellan gum (GG) solution to study the in-situ formation of hydrogel-particle composites. The particles provide multiple functionalities: 1) they efficiently crosslink GG to induce hydrogel formation through the release of the divalent cations (Ca2+/Mg2+) known to bind to GG polymer chains; 2) they enhance mechanical properties of the hydrogel from 2 up to 100 kPa; 3) the samples most efficiently promoting cell growth were found to contain two types of minerals: vaterite and hydroxymagnesite, which enhanced cells proliferation and hydroxyapatite formation. The results demonstrate that such composite materials are attractive candidates for applications in bone regeneration.

Electron Beam-Treated Enzymatically Mineralized Gelatin Hydrogels for Bone Tissue Engineering.

Biological hydrogels are highly promising materials for bone tissue engineering (BTE) due to their high biocompatibility and biomimetic characteristics. However, for advanced and customized BTE, precise tools for material stabilization and tuning material properties are desired while optimal mineralisation must be ensured. Therefore, reagent-free crosslinking techniques such as high energy electron beam treatment promise effective material modifications without formation of cytotoxic by-products. In the case of the hydrogel gelatin, electron beam crosslinking further induces thermal stability enabling biomedical application at physiological temperatures. In the case of enzymatic mineralisation, induced by Alkaline Phosphatase (ALP) and mediated by Calcium Glycerophosphate (CaGP), it is necessary to investigate if electron beam treatment before mineralisation has an influence on the enzymatic activity and thus affects the mineralisation process. The presented study investigates electron beam-treated gelatin hydrogels with previously incorporated ALP and successive mineralisation via incubation in a medium containing CaGP. It could be shown that electron beam treatment optimally maintains enzymatic activity of ALP which allows mineralisation. Furthermore, the precise tuning of material properties such as increasing compressive modulus is possible. This study characterizes the mineralised hydrogels in terms of mineral formation and demonstrates the formation of CaP in dependence of ALP concentration and electron dose. Furthermore, investigations of uniaxial compression stability indicate increased compression moduli for mineralised electron beam-treated gelatin hydrogels. In summary, electron beam-treated mineralized gelatin hydrogels reveal good cytocompatibility for MG-63 osteoblast like cells indicating a high potential for BTE applications.

Phloroglucinol-enhanced whey protein isolate hydrogels with antimicrobial activity for tissue engineering.

Aging populations in developed countries will increase the demand for implantable materials to support tissue regeneration. Whey Protein Isolate (WPI), derived from dairy industry by-products, can be processed into hydrogels with the following desirable properties for applications in tissue engineering: (i) ability to support adhesion and growth of cells; (ii) ease of sterilization by autoclaving and (iii) ease of incorporation of poorly water-soluble drugs with antimicrobial activity, such as phloroglucinol (PG), the fundamental phenolic subunit of marine polyphenols. In this study, WPI hydrogels were enriched with PG at concentrations between 0 and 20% w/v. PG solubilization in WPI hydrogels is far higher than in water. Enrichment with PG did not adversely affect mechanical properties, and endowed antimicrobial activity against a range of bacteria which occur in healthcare-associated infections (HAI). WPI-PG hydrogels supported the growth of, and collagen production by human dental pulp stem cells and - to a lesser extent - of osteosarcoma-derived MG-63 cells. In summary, enrichment of WPI with PG may be a promising strategy to prevent microbial contamination while still promoting stem cell attachment and growth.

Synthesis and Characterization of Polymer-Based Coatings Modified with Bioactive Ceramic and Bovine Serum Albumin.

This study involves the synthesis of hydroxyapatite and describes the preparation and characterization of polymer coatings based on poly(ethylene glycol) diacrylate and poly(ethylene glycol) and modified with bovine serum albumin and hydroxyapatite. Hydroxyapatite was obtained by wet chemical synthesis and characterized by X-ray diffraction and FTIR spectroscopy, and its Ca/P molar ratio was determined (1.69 ± 0.08). The ceramic and bovine serum albumin were used in the preparation of composite materials with the polymeric matrix. The chemical composition of coatings was characterized with FTIR spectroscopy, and their morphology was recorded with SEM imaging. Moreover, the measurements of surface roughness parameters and stereometric research were performed. The prepared coatings were subjected to in vitro studies in simulated body fluid and artificial saliva. Changes in chemical composition and morphology after immersion were examined with FTIR spectroscopy and SEM imaging. Based on the conducted research, it can be stated that applied modifiers promote the biomineralization process. The roughness analysis confirmed prepared materials were characterized by the micrometer-scale topography. The materials morphology and roughness, and the morphology of the newly formed apatite deposit, were dependent on the type of the used modifier, and the artificial fluid used in in vitro studies.

pH-Sensitive Dairy-Derived Hydrogels with a Prolonged Drug Release Profile for Cancer Treatment.

A novel versatile biocompatible hydrogel of whey protein isolate (WPI) and two types of tannic acid (TAs) was prepared by crosslinking of WPI with TAs in a one-step method at high temperature for 30 min. WPI is one common protein-based preparation which is used for hydrogel formation. The obtained WPI-TA hydrogels were in disc form and retained their integrity after sterilization by autoclaving. Two TA preparations of differing molecular weight and chemical structure were compared, namely a polygalloyl glucose-rich extract-ALSOK 02-and a polygalloyl quinic acid-rich extract-ALSOK 04. Hydrogel formation was observed for WPI solutions containing both preparations. The swelling characteristics of hydrogels were investigated at room temperature at different pH values, namely 5, 7, and 9. The swelling ability of hydrogels was independent of the chemical structure of the added TAs. A trend of decrease of mass increase (MI) in hydrogels was observed with an increase in the TA/WPI ratio compared to the control WPI hydrogel without TA. This dependence (a MI decrease-TA/WPI ratio) was observed for hydrogels with different types of TA both in neutral and acidic conditions (pH 5.7). Under alkaline conditions (pH 9), negative values of swelling were observed for all hydrogels with a high content of TAs and were accompanied by a significant release of TAs from the hydrogel network. Our studies have shown that the release of TA from hydrogels containing ALSOK04 is higher than from hydrogels containing ALSOK 02. Moreover, the addition of TAs, which display a strong anti-cancer effect, increases the cytotoxicity of WPI-TAs hydrogels against the Hep-2 human laryngeal squamous carcinoma (Hep-2 cells) cell line. Thus, WPI-TA hydrogels with prolonged drug release properties and cytotoxicity effect can be used as anti-cancer scaffolds.

Surface functionalization of chitosan as a coating material for orthopaedic applications: A comprehensive review.

Metallic implants have dominated the biomedical implant industries for the past century for load-bearing applications, while the polymeric implants have shown great promise for tissue engineering applications. The surface properties of such implants are critical as the interaction of implant surfaces, and the body tissues may lead to unfavourable reactions. Desired implant properties are biocompatibility, corrosion resistance, and antibacterial activity. A polymer coating is an efficient and economical way to produce such surfaces. A lot of research has been carried out on chitosan (CS)-modified metallic and polymer scaffolds in the last decade. Different methods such as electrophoretic deposition, sol-gel methods, dip coating and spin coating, electrospinning, etc. have been utilized to produce CS coatings. However, a systematic review of chitosan coatings on scaffolds focussing on widely employed techniques is lacking. This review surveys literature concerning the current status of orthopaedic applications of CS for the purpose of coatings. In this review, the various preparation methods of coating, and the role of the surface functionalities in determining the efficiency of coatings are discussed. Effect of nanoparticle additions on the polymeric interfaces and in regulating the properties of surface coatings are also investigated in detail.

Heparin Enriched-WPI Coating on Ti6Al4V Increases Hydrophilicity and Improves Proliferation and Differentiation of Human Bone Marrow Stromal Cells.

Titanium alloy (Ti6Al4V) is one of the most prominent biomaterials for bone contact because of its ability to bear mechanical loading and resist corrosion. The success of Ti6Al4V implants depends on bone formation on the implant surface. Hence, implant coatings which promote adhesion, proliferation and differentiation of bone-forming cells are desirable. One coating strategy is by adsorption of biomacromolecules. In this study, Ti6Al4V substrates produced by additive manufacturing (AM) were coated with whey protein isolate (WPI) fibrils, obtained at pH 2, and heparin or tinzaparin (a low molecular weight heparin LMWH) in order to improve the proliferation and differentiation of bone-forming cells. WPI fibrils proved to be an excellent support for the growth of human bone marrow stromal cells (hBMSC). Indeed, WPI fibrils were resistant to sterilization and were stable during storage. This WPI-heparin-enriched coating, especially the LMWH, enhanced the differentiation of hBMSC by increasing tissue non-specific alkaline phosphatase (TNAP) activity. Finally, the coating increased the hydrophilicity of the material. The results confirmed that WPI fibrils are an excellent biomaterial which can be used for biomedical coatings, as they are easily modifiable and resistant to heat treatments. Indeed, the already known positive effect on osteogenic integration of WPI-only coated substrates has been further enhanced by a simple adsorption procedure.

Phenolic-Enriched Collagen Fibrillar Coatings on Titanium Alloy to Promote Osteogenic Differentiation and Reduce Inflammation.

The adsorption of biomolecules on biomaterial surfaces can promote their integration with surrounding tissue without changing their bulk properties. For biomaterials in bone reconstruction, the promotion of osteogenic differentiation and reduction of inflammation are desirable. Fibrillar coatings are interesting because of fibrils' high surface area-volume ratio, aiding adsorption and adhesion. Fibrils also serve as a matrix for the immobilization of biomolecules with biological activity, such as the phenolic compound phloroglucinol (PG), the subunit of marine polyphenols. The aim of this work was to investigate the influence of PG coatings on fibroblast- and osteoblast-like cells to increase the osseointegration of titanium implants. Collagen fibril coatings, containing PG at low and high concentrations, were produced on titanium alloy (Ti6Al4V) scaffolds generated by additive manufacturing (AM). These coatings, especially PG-enriched coatings, reduced hydrophobicity and modulated the behavior of human osteosarcoma SaOS-2 and mouse embryonic fibroblast 3T3 cell lines. Both osteoblastic and fibroblastic cells spread and adhered well on PG-enriched coatings. Coatings significantly reduced the inflammatory response. Moreover, osteogenic differentiation was promoted by collagen coatings with a high PG concentration. Thus, the enrichment of collagen fibril coatings with PG is a promising strategy to improve Ti6Al4V implants for bone contact in orthopedics and dentistry and is worthy of further investigation.