Fucosylated Chondroitin Sulfates with Rare Disaccharide Branches from the Sea Cucumbers Psolus peronii and Holothuria nobilis: Structures and Influence on Hematopoiesis.

Two fucosylated chondroitin sulfates were isolated from the sea cucumbers Psolus peronii and Holothuria nobilis using a conventional extraction procedure in the presence of papain, followed by anion-exchange chromatography on DEAE-Sephacel. Their composition was characterized in terms of quantitative monosaccharide and sulfate content, and structures were mainly elucidated using 1D- and 2D-NMR spectroscopy. As revealed by the data of the NMR spectra, both polysaccharides along with the usual fucosyl branches contained rare disaccharide branches α-D-GalNAc4S6R-(1→2)-α-L-Fuc3S4R → attached to O-3 of the GlcA of the backbone (R = H or SO3-). The polysaccharides were studied as stimulators of hematopoiesis in vitro using mice bone marrow cells as the model. The studied polysaccharides were shown to be able to directly stimulate the proliferation of various progenitors of myelocytes and megakaryocytes as well as lymphocytes and mesenchymal cells in vitro. Therefore, the new fucosylated chondroitin sulfates can be regarded as prototype structures for the further design of GMP-compatible synthetic analogs for the development of new-generation hematopoiesis stimulators.

Development of Bioactive Scaffolds for Orthopedic Applications by Designing Additively Manufactured Titanium Porous Structures: A Critical Review.

We overview recent findings achieved in the field of model-driven development of additively manufactured porous materials for the development of a new generation of bioactive implants for orthopedic applications. Porous structures produced from biocompatible titanium alloys using selective laser melting can present a promising material to design scaffolds with regulated mechanical properties and with the capacity to be loaded with pharmaceutical products. Adjusting pore geometry, one could control elastic modulus and strength/fatigue properties of the engineered structures to be compatible with bone tissues, thus preventing the stress shield effect when replacing a diseased bone fragment. Adsorption of medicals by internal spaces would make it possible to emit the antibiotic and anti-tumor agents into surrounding tissues. The developed internal porosity and surface roughness can provide the desired vascularization and osteointegration. We critically analyze the recent advances in the field featuring model design approaches, virtual testing of the designed structures, capabilities of additive printing of porous structures, biomedical issues of the engineered scaffolds, and so on. Special attention is paid to highlighting the actual problems in the field and the ways of their solutions.

Influence of the Phase Composition of Titanium Alloys on Cell Adhesion and Surface Colonization.

The pivotal role of metal implants within the host's body following reconstructive surgery hinges primarily on the initial phase of the process: the adhesion of host cells to the implant's surface and the subsequent colonization by these cells. Notably, titanium alloys represent a significant class of materials used for crafting metal implants. This study, however, marks the first investigation into how the phase composition of titanium alloys, encompassing the volume fractions of the α, ß, and ω phases, influences cell adhesion to the implant's surface. Moreover, the research delves into the examination of induced hemolysis and cytotoxicity. To manipulate the phase composition of titanium alloys, various parameters were altered, including the chemical composition of titanium alloys with iron and niobium, annealing temperature, and high-pressure torsion parameters. By systematically adjusting these experimental parameters, we were able to discern the distinct impact of phase composition. As a result, the study unveiled that the colonization of the surfaces of the examined Ti-Nb and Ti-Fe alloys by human multipotent mesenchymal stromal cells exhibits an upward trend with the increasing proportion of the ω phase, concurrently accompanied by a decrease in the α and ß phases. These findings signify a new avenue for advancing Ti-based alloys for both permanent implants and temporary fixtures, capitalizing on the ability to regulate the volume fractions of the α, ß, and ω phases. Furthermore, the promising characteristics of the ω phase suggest the potential emergence of a third generation of biocompatible Ti alloys, the ω-based materials, following the first-generation α-Ti alloys and second-generation ß alloys.

Anti-Cancer Potential of Transiently Transfected HER2-Specific Human Mixed CAR-T and NK Cell Populations in Experimental Models: Initial Studies on Fucosylated Chondroitin Sulfate Usage for Safer Treatment.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in numerous cancer cell types. Therapeutic antibodies and chimeric antigen receptors (CARs) against HER2 were developed to treat human tumors. The major limitation of anti-HER2 CAR-T lymphocyte therapy is attributable to the low HER2 expression in a wide range of normal tissues. Thus, side effects are caused by CAR lymphocyte "on-target off-tumor" reactions. We aimed to develop safer HER2-targeting CAR-based therapy. CAR constructs against HER2 tumor-associated antigen (TAA) for transient expression were delivered into target T and natural killer (NK) cells by an effective and safe non-viral transfection method via nucleofection, excluding the risk of mutations associated with viral transduction. Different in vitro end-point and real-time assays of the CAR lymphocyte antitumor cytotoxicity and in vivo human HER2-positive tumor xenograft mice model proved potent cytotoxic activity of the generated CAR-T-NK cells. Our data suggest transient expression of anti-HER2 CARs in plasmid vectors by human lymphocytes as a safer treatment for HER2-positive human cancers. We also conducted preliminary investigations to elucidate if fucosylated chondroitin sulfate may be used as a possible agent to decrease excessive cytokine production without negative impact on the CAR lymphocyte antitumor effect.

Bioactivity Features of a Zn-1%Mg-0.1%Dy Alloy Strengthened by Equal-Channel Angular Pressing.

The structure, phase composition, corrosion and mechanical properties, as well as aspects of biocompatibility in vitro and in vivo, of a Zn-1%Mg-0.1%Dy alloy after equal-channel angular pressing (ECAP) were studied. The structure refinement after ECAP leads to the formation of elongated α-Zn grains with a width of ~10 µm and of Mg- and Dy-containing phases. In addition, X-ray diffraction analysis demonstrated that ECAP resulted in the formation of the basal texture in the alloy. These changes in the microstructure and texture lead to an increase in ultimate tensile strength up to 262 ± 7 MPa and ductility up to 5.7 ± 0.2%. ECAP slows down the degradation process, apparently due to the formation of a more homogeneous microstructure. It was found that the alloy degradation rate in vivo after subcutaneous implantation in mice is significantly lower than in vitro ones. ECAP does not impair biocompatibility in vitro and in vivo of the Zn-1%Mg-0.1%Dy alloy. No signs of suppuration, allergic reactions, the formation of visible seals or skin ulcerations were observed after implantation of the alloy. This may indicate the absence of an acute reaction of the animal body to the Zn-1%Mg-0.1%Dy alloy in both states.

Spontaneous regression of a metastatic carcinoma transmitted by a kidney graft.

Transmission of a malignancy from a donor's organ to the recipient of the graft is a rare event, though it is a severe complication that can result in a poor outcome. Usually, immunosuppressive therapy is discontinued and the allograft is removed. However, treatment of patients with the disseminated cancers implies that after the graft removal and cessation of the immunosuppression, radiotherapy, chemotherapy, or immunotherapy with alpha-interferon (INF-α) or interleukin-2 (IL-2) are required. The case report presents a clinical case of a transmitted kidney graft with multiple metastases (MTS) in a 31-year-old woman with the spontaneous regression of the metastatic cancer after transplantectomy and cancellation of the immunosuppressive therapy. Obviously, the determining factor is the recognition of the tumor by the effectors of the antitumor immunity due to the human leukocyte antigen (HLA) mismatch between the donor and the recipient. Therefore, cancellation of the immunosuppressive therapy in cases of transferal of a malignancy with a transplanted organ allows the effectors of the immune system to distinguish the tumor as a foreign tissue and effectively eliminate this neoplasm.

Glycosaminoglycans from the Starfish Lethasterias fusca: Structures and Influence on Hematopoiesis.

Crude anionic polysaccharides extracted from the Pacific starfish Lethasterias fusca were purified by anion-exchange chromatography. The main fraction LF, having MW 14.5 kDa and dispersity 1.28 (data of gel-permeation chromatography), was solvolytically desulfated and giving rise to preparation LF-deS with a structure of dermatan core [→3)-ß-d-GalNAc-(1→4)-α-l-IdoA-(1→]n, which was identified according to NMR spectroscopy data. Analysis of the NMR spectra of the parent fraction LF led to identification of the main component as dermatan sulfate LF-Derm →3)-ß-d-GalNAc4R-(1→4)-α-l-IdoA2R3S-(1→ (where R was SO3 or H), bearing sulfate groups at O-3 or both at O-2 and O-3 of α-l-iduronic acid, as well as at O-4 of some N-acetyl-d-galactosamine residues. The minor signals in NMR spectra of LF were assigned as resonances of heparinoid LF-Hep composed of the fragments →4)-α-d-GlcNS3S6S-(1→4)-α-l-IdoA2S3S-(1→. The 3-O-sulfated and 2,3-di-O-sulfated iduronic acid residues are very unusual for natural glycosaminoglycans, and further studies are needed to elucidate their possible specific influence on the biological activity of the corresponding polysaccharides. To confirm the presence of these units in LF-Derm and LF-Hep, a series of variously sulfated model 3-aminopropyl iduronosides were synthesized and their NMR spectra were compared with those of the polysaccharides. Preparations LF and LF-deS were studied as stimulators of hematopoiesis in vitro. Surprisingly, it was found that both preparations were active in these tests, and hence, the high level of sulfation is not necessary for hematopoiesis stimulation in this particular case.

Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro.

A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with chiral amino acid amides at C6 was used for the enzymatic synthesis, and the reaction equilibrium shifted towards the synthesis of arabinonucleosides. The synthesized nucleosides were shown to be resistant to the action of E. coli adenosine deaminase. The antiproliferative activity of the synthesized nucleosides was studied on human acute myeloid leukemia cell line U937. Among all the compounds, the serine derivative exhibited an activity level (IC50 = 16 µM) close to that of Nelarabine (IC50 = 3 µM) and was evaluated as active.

Structure, Biodegradation, and In Vitro Bioactivity of Zn-1%Mg Alloy Strengthened by High-Pressure Torsion.

The effect of high-pressure torsion (HPT) on the microstructure, phase composition, mechanical characteristics, degradation rate, and bioactive properties of the Zn-1%Mg alloy is studied. An ultrafine-grained (UFG) structure with an average grain size of α-Zn equal to 890 ± 26 nm and grains and subgrains of the Mg2Zn11 and MgZn2 phases with a size of 50-100 nm are formed after HPT. This UFG structure leads to an increase in the ultimate tensile strength of the alloy by ~3 times with an increase in elongation to 6.3 ± 3.3% due to the formation of a basal texture. The study of corrosion resistance did not show a significant effect of HPT on the degradation rate of the alloy. In addition, no significant changes in the bioactivity of the alloy after HPT: hemolysis, cellular colonization and Escherichia coli growth inhibition.

Mechanical, Structural, and Biological Characteristics of Polylactide/Wollastonite 3D Printed Scaffolds.

The present work aimed to study the synergistic response of bioresorbable polylactide/bioactive wollastonite scaffolds towards mechanical stability, mesenchymal stromal cell colonization, and antibacterial activity in the physiological environment. Wollastonite was synthesized at 800 °C within 2 h by sol-gel combustion method. The surface area was found to be 1.51 m2/g, and Transmission Electron Microscopy (TEM) micrographs indicated the presence of porous structures. Fused deposition modeling was used to prepare 3D-printed polylactide/wollastonite and polylactide/hydroxyapatite scaffolds. Scanning Electron Microscopy (SEM) micrographs confirmed the interconnected porous structure and complex geometry of the scaffolds. The addition of wollastonite decreased the contact angle of the scaffolds. The mechanical testing of scaffolds examined by computational simulation, as well as machine testing, revealed their non-load-bearing capacity. The chemical constituent of the scaffolds was found to influence the attachment response of different cells on their surface. The incorporation of wollastonite effectively reduced live bacterial attachment, whereas the colonization of mesenchymal cells was improved. This observation confirms polylactide/wollastonite scaffold possesses both bactericidal as well as cytocompatible properties. Thus, the risk of peri-implant bacterial film formation can be prevented, and the biological fixation of the scaffold at the defect site can be enhanced by utilizing these composites.

Perspectives for the Use of Fucoidans in Clinical Oncology.

Fucoidans are natural sulfated polysaccharides that have a wide range of biological functions and are regarded as promising antitumor agents. The activity of various fucoidans and their derivatives has been demonstrated in vitro on tumor cells of different histogenesis and in experiments on mice with grafted tumors. However, these experimental models showed low levels of antitumor activity and clinical trials did not prove that this class of compounds could serve as antitumor drugs. Nevertheless, the anti-inflammatory, antiangiogenic, immunostimulating, and anticoagulant properties of fucoidans, as well as their ability to stimulate hematopoiesis during cytostatic-based antitumor therapy, suggest that effective fucoidan-based drugs could be designed for the supportive care and symptomatic therapy of cancer patients. The use of fucoidans in cancer patients after chemotherapy and radiation therapy might promote the rapid improvement of hematopoiesis, while their anti-inflammatory, immunomodulatory, and anticoagulant effects have the potential to improve the quality of life of patients with advanced cancer.

Novel and Promising Strategies for Therapy of Post-Transplant Chronic GVHD.

Despite the achievements that have increased viability after the transplantation of allogeneic hematopoietic stem cells (aHSCT), chronic graft-versus-host disease (cGVHD) remains the main cause of late complications and post-transplant deaths. At the moment, therapy alternatives demonstrate limited effectiveness in steroid-refractory illness; in addition, we have no reliable data on the mechanism of this condition. The lack of drugs of choice for the treatment of GVHD underscores the significance of the design of new therapies. Improved understanding of the mechanism of chronic GVHD has secured new therapy goals, and organized diagnostic recommendations and the development of medical tests have ensured a general language and routes for studies in this field. These factors, combined with the rapid development of pharmacology, have helped speed up the search of medicines and medical studies regarding chronic GVHD. At present, we can hope for success in curing this formidable complication. This review summarizes the latest clinical developments in new treatments for chronic GVHD.

Antiviral Cell Products against COVID-19: Learning Lessons from Previous Research in Anti-Infective Cell-Based Agents.

COVID-19 is a real challenge for the protective immunity. Some people do not respond to vaccination by acquiring an appropriate immunological memory. The risk groups for this particular infection such as the elderly and people with compromised immunity (cancer patients, pregnant women, etc.) have the most serious problems in developing an adequate immune response. Therefore, dendritic cell (DC) vaccines that are loaded ex vivo with SARS-CoV-2 antigens in the optimal conditions are promising for immunization. Lymphocyte effector cells with chimeric antigen receptor (CAR lymphocytes) are currently used mainly as anti-tumor treatment. Before 2020, few studies on the antiviral CAR lymphocytes were reported, but since the outbreak of SARS-CoV-2 the number of such studies has increased. The basis for CARs against SARS-CoV-2 were several virus-specific neutralizing monoclonal antibodies. We propose a similar, but basically novel and more universal approach. The extracellular domain of the immunoglobulin G receptors will be used as the CAR receptor domain. The specificity of the CAR will be determined by the antibodies, which it has bound. Therefore, such CAR lymphocytes are highly universal and have functional activity against any infectious agents that have protective antibodies binding to a foreign surface antigen on the infected cells.

Depolymerization of a fucosylated chondroitin sulfate from Cucumaria japonica: Structure and activity of the product.

Fucosylated chondroitin sulfate CJ from the body wall of sea cucumber Cucumaria japonica was depolymerized by the treatment with H2O2 in the presence of Cu(OAc)2. The molecular weight of the polysaccharide was decreased from 32 kDa to 5 kDa. The product CJ-DP was shown to contain l-Fuc, d-GalNAc, d-GlcA, and sulfate in molar proportions of 0.96:0.90:1.00:5.4, which were quite similar to those of the parent polysaccharide CJ. The NMR analysis revealed that CJ-DP, like the parent polysaccharide CJ, consisted of both branched →4)-[3-O-α-l-Fuc]-ß-d-GlcA-(1 â†’ 3)-ß-d-GalNAc-(1→ and linear →4)-ß-d-GlcA-(1 â†’ 3)-ß-d-GalNAc-(1→ repeating blocks. Sulfate groups occupy O-4 and the majority of O-6 of GalNAc, as well as O-3 of GlcA, in linear blocks and different positions in Fuc branches. This result indicates that depolymerization practically does not diminish the amount of branches and sulfate groups in the product. Both polysaccharides CJ and CJ-DP demonstrated anticoagulant and hematopoiesis-stimulatory activities in vitro.

Structure Optimization of a Fe-Mn-Pd Alloy by Equal-Channel Angular Pressing for Biomedical Use.

In this work, a Fe-Mn-Pd alloy was produced by methods of equal channel angular pressing (ECAP) in order to obtain an alloy with a high rate of degradation for the development of biodegradable devices. Special efforts were made to the obtaining of an ultrafine-grained structure of alloys in a fully austenitic state at temperatures of 300 °C and 450 °C. Further investigation of its effect on the corrosion rate and mechanical properties was carried out. The formation of an austenitic structure with structural element sizes of 100-250 nm after deformation was confirmed by X-ray diffraction analysis. ECAP proved to be the reason for a significant increase in strength with maximum σUTS = 1669 MPa and σYS = 1577 MPa while maintaining satisfactory plasticity. The alloy degradation rate was investigated using the potentiodynamic polarization analysis. The corrosion rate of the alloy after ECAP (~1 mm/y) is higher than that of the coarse-grained state and significantly higher than that of annealed iron (~0.2 mm/y). ECAP in both modes did not impair the biocompatibility of the Fe-Mn-Pd alloy and the colonization of the sample surface by cells.

Chondroitin Sulfate and Fucosylated Chondroitin Sulfate as Stimulators of Hematopoiesis in Cyclophosphamide-Induced Mice.

The immunosuppression and inhibition of hematopoiesis are considered to be reasons for the development of complications after intensive chemotherapy and allogeneic hematopoietic stem cell transplantation. Chondroitin sulfate (CS), isolated from the fish Salmo salar, and fucosylated chondroitin sulfate (FCS), isolated from the sea cucumber Apostichopus japonicus, were studied for their roles as stimulators of hematopoiesis in a model of cyclophosphamide-induced immunosuppression in mice. The recombinant protein r G-CSF was applied as a reference. The studied polysaccharides were shown to stimulate the release of white and red blood cells, as well as platelets from bone marrow in immunosuppressed mice, while r G-CSF was only responsible for the significant increase in the level of leucocytes. The analysis of different populations of leucocytes in blood indicated that r G-CSF mainly stimulated the production of neutrophils, whereas in the cases of the studied saccharides, increases in the levels of monocytes, lymphocytes and neutrophils were observed. The normalization of the level of the pro-inflammatory cytokine IL-6 in the serum and the recovery of cell populations in the spleen were observed in immunosuppressed mice following treatment with the polysaccharides. An increase in the proliferative activity of hematopoietic cells CD34(+)CD45(+) was observed following ex vivo polysaccharide exposure. Further study on related oligosaccharides regarding their potential as promising drugs in the complex prophylaxis and therapy of hematopoiesis inhibition after intensive chemotherapy and allogeneic hematopoietic stem cell transplantation seems to be warranted.

Anti-tumour activity of Mg-6%Ag and Mg-10%Gd alloys in mice with inoculated melanoma.

Cytotoxicity in vitro and anti-tumour activity in vivo of magnesium alloys Mg-6%Ag and Mg-10%Gd was studied. It was shown that specifically designed and thermomechanically processed Mg alloys produced a sizeable cytotoxic effect on PC-3 line tumour cells in vitro through inhibition of their proliferation. A pronounced grain refinement in combination with the formation of second phases and precipitates attained by means of equal-channel angular pressing (ECAP) accellerated the degradation and gave rise to enhanced anti-tumour activity of both alloys. The gadolinium-containing alloy outperformed the silver-containing one substantially. In an in vivo assay, intratumoural implantation of pins made from both alloys in the homogenised and the ECAP states in mice with inoculated B16 melanoma gave rise to an indubitable anti-tumour effect. It was documented in a decrease of Ki-67(+) cells and the occurrence of regions of destruction of tumoural tissue that were filled with gas evolving in the course of biodegradation of the implants. The data obtained suggest that intratumoural implantation of gadolinium-containing magnesium alloys can be considered for therapy of inoperable or chemoresistant forms of cancer.

Potential Use of Mesenchymal Multipotent Cells for Hemopoietic Stem Cell Transplantation: Pro and Contra.

The potential of mesenchymal multipotent (stem) cells (MSC) to modify immune reactions and mediate hematopoiesis boosted great interest for their use in allogeneic hemopoietic stem cell transplantation. Because of MSC production of a wide range of cytokines and growth factors, these cells are included in the therapy of graft-versus-host disease (GVHD). A number of clinical studies have demonstrated safety and efficacy of MSC-based therapy in acute GVHD. Japan and some other countries approved biomedical cell products on the base of allogeneic bone marrow (BM) MSCs as medical agents for acute GVHD treatment. Besides, MSCs may form BM stroma and improve hematopoiesis. Simultaneous transplantation of hematopoietic stem cells and MSCs effectively improved engraftment and prevented GVHD in transplantation of umbilical cord blood and human leukocyte antigens-incompatible BM stem cells. The review presents the analysis of clinical studies of MSCs in allogeneic hematopoietic stem cell transplantation and discusses different approaches for improvement of MSC-based GVHD treatment and prophylaxis.

Biomineralization, dissolution and cellular studies of silicate bioceramics prepared from eggshell and rice husk.

The current investigation aims to replace the synthetic starting materials with biowaste to synthesize and explore three different silicate bioceramics. Pure silica from rice husk was extracted by decomposition of rice husk in muffle furnace followed by alkali treatment and acid precipitation. Raw eggshell and extracted silica were utilized for the preparation of wollastonite, diopside and forsterite by the solid-state method. The TG-DSC analysis shows that the crystallization temperature of wollastonite, diopside and forsterite was found to be 883 °C, 870 °C and 980 °C, respectively. The phase purity of wollastonite was attained at 1100 °C whereas diopside and forsterite were composed of secondary phases even after calcination at 1250 °C and 1300 °C respectively. All three materials behaved differently when exposed to the physiological environment, as wollastonite exhibited remarkable apatite deposition within 3 days whereas a distinct apatite phase was noticed on the surface of diopside after 2 weeks and forsterite shows the formation of apatite phase after five weeks of immersion. The rapid dissolution of Mg2+ ion from forsterite lowered the leaching of silicate ions into the simulated body fluid leading to poor apatite deposition over its surface. Chemical composition was found to plays a key role in the biomineralization ability of these bioceramics. Hemolysis and Lactate Dehydrogenase (LDH) release assays were performed to evaluate the hemocompatibility of silicate ceramics cultured at different concentrations (62.5, 125, and 250 µg/mL) with red blood cells and mononuclear leucocytes (MLs) of mice. The hemolytic activity of all the tested bioceramics was insignificant (less than 1%). The interaction between diopside and mouse multipotent mesenchymal stromal cells (MMSCs) caused a negligible increase in the number of apoptosis-associated Annexin V-binding cells whereas forsterite and wollastonite induced an increase in the number of the apoptotic cells only at the concentration of 250 µg/mL. The LDH assay did not show statistically significant changes in the proliferation of MMSCs after treatment with the bioceramics at the tested concentrations when compared to control (p > 0.05). This finding showed that the death of a part of cells during the first 24 h of incubation did not prevent the proliferation of MMSCs incubated with diopside, forsterite and wollastonite for 72 h.

Biocompatibility and Physico-Chemical Properties of Highly Porous PLA/HA Scaffolds for Bone Reconstruction.

The major problem in bone tissue engineering is the development of scaffolds which can simultaneously meet the requirements of porous structure, as well as have the ability to guide the regeneration of damaged tissue by biological fixation. Composites containing biodegradable matrix and bioactive filler are the new hope in this research field. Herein we employed a simple and facile solvent casting particulate-leaching method for producing polylactide acid/hydroxyapatite (PLA/HA) composites at room temperature. FT-IR analysis confirmed the existence of necessary functional groups associated with the PLA/HA composite, whereas energy-dispersive X-ray (EDX) spectra indicated the uniform distribution of hydroxyapatite particles in the polymer matrix. The beehive-like surface morphology of the composites revealed the presence of macropores, ranged from 300 to 400 µm, whereas the thickness of the pores was noticed to be 1-2 µm. The total porosity of the scaffolds, calculated by hydrostatic weighing, was found to be 79%. The water contact angle of pure PLA was decreased from 83.6 ± 1.91° to 62.4 ± 4.17° due to the addition of hydroxyapatite in the polymer matrix. Thus, the wettability of the polymeric biomaterial could be increased by preparing their composites with hydroxyapatite. The adhesion of multipotent mesenchymal stromal cells over the surface of PLA/HA scaffolds was 3.2 times (p = 0.03) higher than the pure PLA sample. Subcutaneous implantation in mice demonstrated a good tolerance of all tested porous scaffolds and widespread ingrowth of tissue into the implant pores. HA-containing scaffolds showed a less pronounced inflammatory response after two weeks of implantation compared to pure PLA. These observations suggest that PLA/HA composites have enormous potential for hard tissue engineering and restoring maxillofacial defects.