Creating bioactive materials for bone tissue regeneration and augmentation remains a pertinent challenge. One of the most promising and rapidly advancing approaches involves the use of low-temperature ceramics that closely mimic the natural composition of the extracellular matrix of native bone tissue, such as Hydroxyapatite (HAp) and its phase precursors (Dicalcium Phosphate Dihydrate—DCPD, Octacalcium Phosphate—OCP, etc.). However, despite significant scientific interest, the current knowledge and understanding remain limited regarding the impact of these ceramics not only on reparative histogenesis processes but also on the immunostimulation and initiation of local aseptic inflammation leading to material rejection. Using the stable cell models of monocyte-like (THP-1ATRA) and macrophage-like (THP-1PMA) cells under the conditions of LPS-induced model inflammation in vitro, the influence of DCPD, OCP, and HAp on cell viability, ROS and intracellular NO production, phagocytosis, and the secretion of pro-inflammatory cytokines was assessed. The results demonstrate that all investigated ceramic particles exhibit biological activity toward human macrophage and monocyte cells in vitro, potentially providing conditions necessary for bone tissue restoration/regeneration in the peri-implant environment in vivo. Among the studied ceramics, DCPD appears to be the most preferable for implantation in patients with latent inflammation or unpredictable immune status, as this ceramic had the most favorable overall impact on the investigated cellular models.

The clinical success of calcium phosphate bone grafts (CPs) largely depends on the body’s immune response. However, traditional biocompatibility tests use healthy organisms and cannot predict effectiveness in patients with common chronic inflammatory diseases. This study examines how inflammation modulates the immune response, in vitro and in vivo, to low-temperature biomimetic CPs: dicalcium phosphate dihydrate (DCPD), octacalcium phosphate (OCP), and hydroxyapatite (HAp). In vitro studies involved human monocytes, macrophages, lymphocytes, and mesenchymal stromal cells (MSCs), with or without pro-inflammatory activation. In vivo biocompatibility was assessed via subcutaneous implantation in rats, with or without Complete Freund’s Adjuvant (CFA)-induced inflammation. Under normal conditions, all CP caused minimal immune reactivity. Inflammation-activated macrophages, however, triggered an acute reaction with significantly increased TNF-α and IL-1β secretion. Healthy and inflamed animals showed sharp contrasts. Although all materials exhibited thickened fibrous capsules during inflammation, biocompatibility varied markedly: DCPD performed best by promoting angiogenesis with minimal inflammation; HAp provoked the most severes response, including tissue necrosis and signs of rejection; OCP showed intermediate effects, with angiogenesis but notable fibrosis. Inflammatory processes critically influence CP biocompatibility; materials biocompatible in healthy organisms can induce fibrosis or rejection under inflammation. Disease-relevant, immune-challenged models are essential to predict clinical efficacy and safety.

One of the key factors of the interaction ‘osteoplastic material—organism’ is the state of the implant surface. Taking into account the fact that the equilibrium in regeneration conditions is reached only after the reparative histogenesis process is completed, the implant surface is constantly modified. This work is devoted to the numerical description of the dynamic bilateral material–medium interaction under close to physiological conditions, as well as to the assessment of the comparability of the model with in vitro and in vivo experimental results. The semi-empirical model obtained on the basis of chemical kinetics allows us to describe numerically the processes occurring in the in vitro systems and extrapolates well to assess the behavior of dicalcium phosphate dihydrate (DCPD) material under conditions of ectopic (subcutaneous) implantation in Wistar rats. It is shown that an experiment conducted using a perfusion–diffusion bioreactor in a cell culture medium with the addition of fetal bovine serum (FBS) allows for achieving morphologically and chemically identical changes in the surface of the material in comparison with the real organism. This fact opens up wide possibilities for the creation of an analog of a ‘laboratory-on-a-chip’ and the transition from classical in vivo models to more controlled and mathematically based in vitro systems.

In the present study, the efficiency of a biomimetic approach by coating demineralized bone matrix (DBM) amorphous calcium phosphate (DBM+CaP), including its combination with serum albumin (DBM+CaP+BSA), was investigated. The intact structure of DBM promotes the transformation of amorphous calcium phosphate (CaP) into DPCD with a characteristic plate shape and particle size of 5–35 µm. The inclusion of BSA in the coating resulted in a better and more uniform distribution of CaP on the surface of DBM trabeculae. MG63 cells showed that both the obtained forms of CaP and its complex with BSA did not exhibit cytotoxicity up to a concentration of 10 mg/ml in vitro. Ectopic (subcutaneous) implantation in rats revealed pronounced biocompatibility, as well as strong osteoconductive, osteoinductive, and osteogenic effects for both DBM+CaP and DBM+CaP+BSA, but more pronounced effects for DBM+CaP+BSA. In addition, for the DBM+CaP+BSA samples, a pronounced full physiological intrafibrillar biomineralization and proangiogenic effect with the formation of bone-morrow-like niches, accompanied by pronounced processes of intramedullary hematopoiesis, indicating a powerful osteogenic effect of this composite have been achieved.

A method for creating bioactive coatings for implants is proposed. These coatings consist of a plasma-coated hydroxyapatite layer and a dicalcium phosphate dihydrate transition layer deposited on top. This layer is then hydrolyzed to produce octacalcium phosphate (where Me = Mg²⁺, Sr²⁺, Ba²⁺) doped with divalent metal ions. X-ray diffraction analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy revealed that strontium cations isomorphically replace calcium in the octacalcium phosphate structure, while magnesium and barium ions inhibit the phase transformation of dicalcium phosphate dihydrate into octacalcium phosphate, forming amorphous phases. An in vitro study in a simulated physiological environment of SBF demonstrated the ability of coatings based on octacalcium phosphate doped with magnesium, barium and strontium cations to biomineralize, indicating their increased bioactive potential compared to bioinert hydroxyapatite.