Three-dimensional Porous Scaffolds Research Articles

Silver Nanoparticles and Simvastatin-Loaded PLGA-Coated Hydroxyapatite/Calcium Carbonate Scaffolds.

The need to develop synthetic bone substitutes with structures, properties, and functions similar to bone and capable of preventing microbial infections is still an ongoing challenge. This research is focused on the preparation and characterization of three-dimensional porous scaffolds based on hydroxyapatite (HA)-functionalized calcium carbonate loaded with silver nanoparticles and simvastatin (SIMV). The scaffolds were prepared using the foam replica method, with a polyurethane (PU) sponge as a template, followed by successive polymer removal and sintering. The scaffolds were then coated with poly(lactic-co-glycolic) acid (PLGA) to improve mechanical properties and structural integrity, and loaded with silver nanoparticles and SIMV. The scaffolds were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), ATR FT-IR, and silver and SIMV loading. Moreover, the samples were analyzed by Brillouin and Raman microscopy. Finally, in vitro bioactivity, SIMV and silver release, and antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis were evaluated. From the Brillouin spectra, samples showed characteristics analogous to those of bone tissue. They exhibited new hydroxyapatite growth, as evidenced by SEM, and good antimicrobial activity against the tested bacteria. In conclusion, the obtained results demonstrate the potential of the scaffolds for application in bone repair.

In-situ building of multiscale porous NiFeZn/NiZn-Ni heterojunction for superior overall water splitting

The development of efficient nonprecious bifunctional electrocatalysts for water electrolysis is crucial to enhance the sluggish kinetics of the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). A self-supporting, multiscale porous NiFeZn/NiZn-Ni catalyst with a triple interface heterojunction on nickel foam (NF) (NiFeZn/NiZn-Ni/NF) was in-situ fabricated using an electroplating−annealing−etching strategy. The unique multi- interface engineering and three-dimensional porous scaffold significantly modify the mass transport and electron interaction, resulting in superior bifunctional electrocatalytic performance for water splitting. The NiFeZn/NiZn-Ni/NF catalyst demonstrates low overpotentials of 187 mV for HER and 320 mV for OER at a current density of 600 mA/cm², along with high durability over 150 h in alkaline solution. Furthermore, an electrolytic cell assembled with NiFeZn/NiZn-Ni/NF as both the cathode and anode achieves the current densities of 600 and 1000 mA/cm2 at cell voltages of 1.796 and 1.901 V, respectively, maintaining the high stability at 50 mA/cm2 for over 100 h. These findings highlight the potential of NiFeZn/NiZn-Ni/NF as a cost-effective and highly efficient bifunctional electrocatalyst for overall water splitting.

The Story, Properties and Applications of Bioactive Glass “1d”: From Concept to Early Clinical Trials

Bioactive glasses in the CaO–MgO–Na2O–P2O5–SiO2–CaF2 system are highly promising materials for bone and dental restorative applications. Furthermore, if thermally treated, they can crystallize into diopside–fluorapatite–wollastonite glass-ceramics (GCs), which exhibit appealing properties in terms of mechanical behaviour and overall bone-regenerative potential. In this review, we describe and critically discuss the genesis, development, properties and applications of bioactive glass “1d” and its relevant GC derivative products, which can be considered a good example of success cases in this class of SiO2/CaO-based biocompatible materials. Bioactive glass 1d can be produced by melt-quenching in the form of powder or monolithic pieces, and was also used to prepare injectable pastes and three-dimensional porous scaffolds. Over the past 15 years, it was investigated by the authors of this article in a number of in vitro, in vivo (with animals) and clinical studies, proving to be a great option for hard tissue engineering applications.

Three-dimensional porous polycaprolactone/chitosan/bioactive glass scaffold for bone tissue engineering

Three-dimensional (3D) porous scaffolds based on polycaprolactone (PCL)/chitosan (CS)/bioactive glass (BG) nanoparticle composites were fabricated by the freeze-drying technique for bone tissue engineering. The physiochemical properties of the developed PCL/CS/BG scaffolds were studied using FTIR, XRD, EDX and SEM. Furthermore, the swelling degree, porosity, water retention ability, compression strength, in vitro biodegradation, bioactivity and biocompatibility of the scaffolds were examined. The PCL/CS/BG scaffolds with 4 wt. % of BG content presented adequate pore size (106 μm), porosity (156%), water swelling degree (128%), water retention ability (179%), compressive strength (3.7 MPa) and controlled degradation behavior, which could be ideal for bone tissue engineering. The PCL/CS/BG composite scaffolds showed good antimicrobial activity against both test bacteria and fungi. The MTT assay demonstrated the biocompatibility of PCL/CS/BG scaffolds against C3H10T1/2 cell line. The Alizarin red staining assay confirmed the osteogenic activity of the PCL/CS/BG scaffolds.

Tailored edible 3D porous scaffolds constructed by Pickering emulgel templating for cell-cultured fish meat

Cell-cultured fish meat have emerged as an innovative approach to resolving the issues in response to consumer demand. Food-grade scaffolds, which not only serve as the “comfortable home” for stem cells but also endow the final product with meat-like texture, play a vital role in the construction of cell-cultured fish meat. In this study, pea protein, an abundant and inexpensive plant protein, is used to construct edible three-dimensional (3D) porous scaffolds, which exhibit desirable stem cell proliferation and differentiation performance. Our findings demonstrate that it is feasible to apply the Pickering emulgel templating combined with double-crosslinking to the preparation of cell-cultured fish meat scaffolds. The pore structure of 3D porous scaffolds can be altered by varying the emulsification parameters on demand. The Pickering emulgels with large droplet size (around 40 μm) are conducive to the formation of 3D porous scaffolds with large enough pore size for the growth of stem cells. The now available result help to explore the plant protein-derived scaffolds, provide insights into the development of Pickering emulgel-based 3D porous scaffolds and illuminate the relationship between the structural characteristics of scaffolds and the biological functions of stem cells.

Silver phosphate-modified carbonate apatite honeycomb scaffolds for anti-infective and pigmentation-free bone tissue engineering

Bone regeneration using synthetic materials has a high rate of surgical site infection, resulting in severe pain for patients and often requiring revision surgery. We propose Ag3PO4-based surface modification and structural control of scaffolds for preventing infections in bone regeneration. We demonstrated the differences in toxicity and antibacterial activity between in vitro and in vivo studies and determined the optimal silver content in terms of overall anti-infection effects, bone regeneration, toxicity, and pigmentation. A honeycomb structure comprising osteoconductive and resorbable carbonate apatite (CAp) was used as the base scaffold. CAp in the scaffold surface was partially replaced with different concentrations of Ag3PO4 via controlled dissolution-precipitation reactions in an AgNO3 solution. Both bone regeneration and infection prevention were achieved at 860–2300 ppm of silver. Despite the absence of Ag3PO4, honeycomb scaffolds were less susceptible to infection, even under conditions where infection occurs in clinically used three-dimensional porous scaffolds. Regardless of in vitro cytotoxicity at >5200 ppm of silver, increasing the silver content to 21,000 ppm did not adversely affect in vivo bone formation and scaffold resorption or cause acute systemic toxicity. Rather, bone formation was enhanced with 5200 ppm of silver. However, pigmentation was observed at that concentration. Hence, we concluded that the optimal silver concentration range is 860–2300 ppm for anti-infective and pigmentation-free bone regeneration. Bone regeneration was achieved via surface modification, resulting in the rapid release of silver ions immediately after implantation, followed by gradual release over several months. The scaffold structure may also aid in preventing bacterial growth within the scaffolds.

Methacrylated Carboxymethyl Chitosan Scaffold Containing Icariin-Loaded Short Fibers for Antibacterial, Hemostasis, and Bone Regeneration.

Bone defects typically result in bone nonunion, delayed or nonhealing, and localized dysfunction, and commonly used clinical treatments (i.e., autologous and allogeneic grafts) have limited results. The multifunctional bone tissue engineering scaffold provides a new treatment for the repair of bone defects. Herein, a three-dimensional porous composite scaffold with stable mechanical support, effective antibacterial and hemostasis properties, and the ability to promote the rapid repair of bone defects was synthesized using methacrylated carboxymethyl chitosan and icariin-loaded poly-l-lactide/gelatin short fibers (M-CMCS-SFs). Icariin-loaded SFs in the M-CMCS scaffold resulted in the sustained release of osteogenic agents, which was beneficial for mechanical reinforcement. Both the porous structure and the use of chitosan facilitate the effective absorption of blood and fluid exudates. Moreover, its superior antibacterial properties could prevent the occurrence of inflammation and infection. When cultured with bone mesenchymal stem cells, the composite scaffold showed a promotion in osteogenic differentiation. Taken together, such a multifunctional composite scaffold showed comprehensive performance in antibacterial, hemostasis, and bone regeneration, thus holding promising potential in the repair of bone defects and related medical treatments.

A hierarchical porous structure integrated three-dimensional electrochemical biosensor for cell culture and real-time monitoring

Three-dimensional (3D) porous scaffolds are arousing tremendous interests in tissue engineering, in-vitro biological models and drug discovery for the potential on integration in-vivo 3D culture stimulation and real-time electrochemical sensing. However, the development on this field is still hindered by the lack of basic 3D conductive materials, unsatisfactory electrochemical performance and complicated construction strategy. Herein, we developed a hierarchical porous 3D electrochemical biosensor with facile preparation strategy for cell culture and real-time detection of cell-released molecules. In this biosensor, the micropores and nanopores were concurrently integrated within the Ni foam 3D porous scaffold, through which the fast mass transfer and the large specific surface area can be accomplished. As a proof of concept, the sensing materials, Pt nanoparticles were functionalized on the 3D porous scaffold. The fabricated biosensor presented a wide linear range from 200 nM to 20 μM with a high sensitivity of 423.1 nA/μM toward hydrogen peroxide. More importantly, HeLa cells cultured thereon demonstrated high viability and the cell-released H2O2 were also real-time monitored, illustrating its great application prospects on the in-vivo 3D modeling systems.

Tendon Decellularized Matrix Modified Fibrous Scaffolds with Porous and Crimped Microstructure for Tendon Regeneration.

Current engineered synthetic scaffolds fail to functionally repair and regenerate ruptured native tendon tissues, partly because they cannot satisfy both the unique biological and biomechanical properties of these tissues. Ideal scaffolds for tendon repair and regeneration need to provide porous topographic structures and biological cues necessary for the efficient infiltration and tenogenic differentiation of embedded stem cells. To obtain crimped and porous scaffolds, highly aligned poly(l-lactide) fibers were prepared by electrospinning followed by postprocessing. Through a mild and controlled hydrogen gas foaming technique, we successfully transformed the crimped fibrous mats into three-dimensional porous scaffolds without sacrificing the crimped microstructure. Porcine derived decellularized tendon matrix was then grafted onto this porous scaffold through fiber surface modification and carbodiimide chemistry. These biofunctionalized, crimped, and porous scaffolds supported the proliferation, migration, and tenogenic induction of tendon derived stem/progenitor cells, while enabling adhesion to native tendons. Together, our data suggest that these biofunctionalized scaffolds can be exploited as promising engineered scaffolds for the treatment of acute tendon rupture.

Meniscal repair with additive manufacture of bioresorbable polymer: From physicochemical characterization to implantation of 3D printed poly (L-co-D, L lactide-co-trimethylene carbonate) with autologous stem cells in rabbits.

Three-dimensional (3D) structures are actually the state-of-the-art technique to create porous scaffolds for tissue engineering. Since regeneration in cartilage tissue is limited due to intrinsic cellular properties this study aims to develop and characterize three-dimensional porous scaffolds of poly (L-co-D, L lactide-co-trimethylene carbonate), PLDLA-TMC, obtained by 3D fiber deposition technique. The PLDLA-TMC terpolymer scaffolds (70:30), were obtained and characterized by scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, thermal gravimetric analysis, compression mechanical testing and study on in vitro degradation, which showed its amorphous characteristics, cylindrical geometry, and interconnected pores. The in vitro degradation study showed significant loss of mechanical properties compatible with a decrease in molar mass, accompanied by changes in morphology. The histocompatibility association of mesenchymal stem cells from rabbit's bone marrow, and PLDLA-TMC scaffolds, were evaluated in the meniscus regeneration, proving the potential of cell culture at in vivo tissue regeneration. Nine New Zealand rabbits underwent total medial meniscectomy, yielding three treatments: implantation of the seeded PLDLA-TMC scaffold, implantation of the unseeded PLDLA-TMC and negative control (defect without any implant). After 24weeks, the results revealed the presence of fibrocartilage in the animals treated with polymer. However, the regeneration obtained with the seeded PLDLA-TMC scaffolds with mesenchymal stem cells had become intimal to mature fibrocartilaginous tissue of normal meniscus both macroscopically and histologically. This study demonstrated the effectiveness of the PLDLA-TMC scaffold in meniscus regeneration and the potential of mesenchymal stem cells in tissue engineering, without the use of growth factors. It is concluded that bioresorbable polymers represent a promising alternative for tissue regeneration.

Development of porous hydroxyapatite/PVA/gelatin/alginate hybrid flexible scaffolds with improved mechanical properties for bone tissue engineering

Porous scaffolds based on gelatin and hydroxyapatite particles (HAp) are promising for applications in bone tissue engineering and regenerative medicine. However, they are not ideal for stress and shock protection due to low compressive strength, brittleness, and poor toughness. Herein, we developed porous hybrid scaffolds by combining multiple components into a single bone scaffold, including hydroxyapatite nanoparticles (HAp NPs), alginate, polyvinyl alcohol (PVA), and gelatin with different gelatin/PVA composition ratios. HAp NPs were synthesized in situ in PVA solution and scaffolds were fabricated using a freeze-drying method. The results showed good physicochemical properties of the scaffolds: formation of pure HAp NPs phase, high porosity, large pore sizes, large swelling capacity depending on varying gelatin/PVA ratios, as well as a long-term degradation rate up to 28 days. The porous scaffolds exhibited compressive strength close to the cancellous bone with stress-strain behavior exhibiting three-stage flexible behavior indicating improved fracture resistance with an energy absorbing capability up to 1.9 MJ/m3. The scaffolds have a yield strength of 70–403 kPa, a compressive strength at 65 % strain of 0.96–1.80 MPa, a nonporous elastic modulus of 10.44–12.40 GPa, and a densification strain of approximately 0.92 %. This work develops three-dimensional (3D) porous hybrid bone scaffolds with mechanical strength within the minimum compressive strength of cancellous bone and mechanical energy absorption capacity favor for cancellous bone repair, bone tissue engineering, and regenerative medicine applications.

An Overview on the Big Players in Bone Tissue Engineering: Biomaterials, Scaffolds and Cells.

Presently, millions worldwide suffer from degenerative and inflammatory bone and joint issues, comprising roughly half of chronic ailments in those over 50, leading to prolonged discomfort and physical limitations. These conditions become more prevalent with age and lifestyle factors, escalating due to the growing elderly populace. Addressing these challenges often entails surgical interventions utilizing implants or bone grafts, though these treatments may entail complications such as pain and tissue death at donor sites for grafts, along with immune rejection. To surmount these challenges, tissue engineering has emerged as a promising avenue for bone injury repair and reconstruction. It involves the use of different biomaterials and the development of three-dimensional porous matrices and scaffolds, alongside osteoprogenitor cells and growth factors to stimulate natural tissue regeneration. This review compiles methodologies that can be used to develop biomaterials that are important in bone tissue replacement and regeneration. Biomaterials for orthopedic implants, several scaffold types and production methods, as well as techniques to assess biomaterials' suitability for human use-both in laboratory settings and within living organisms-are discussed. Even though researchers have had some success, there is still room for improvements in their processing techniques, especially the ones that make scaffolds mechanically stronger without weakening their biological characteristics. Bone tissue engineering is therefore a promising area due to the rise in bone-related injuries.

Soy conglycinin amyloid fibril and chitosan complex scaffold for cultivated meat application

This study addresses the critical need in cultivated meat production for suitable scaffolds that support the growth and differentiation of muscle cells. We explore the synergy of soy conglycinin (7S) amyloid protein fibrils and chitosan to create three-dimensional (3D) porous scaffolds, specifically designed for this application. By varying the molecular weight and deacetylation degrees of chitosan, we employed a controlled temperature water annealing method to produce these complex scaffolds. The formation mechanism of the 7S-chitosan scaffolds was elucidated through molecular simulation and Fourier-transform infrared (FTIR) analysis. Characterization of the scaffolds revealed pore sizes within the 50–250 μm range, porosities from 71% to 78%, and compressive moduli varying between 4.8 and 15.3 kPa, dependent on the chitosan's deacetylation degree and molecular weight. Notably, these scaffolds maintained structural integrity in refrigerated Phosphate Buffered Saline (PBS) for up to three months and effectively supported the growth and differentiation of C2C12 mouse skeletal muscle cells without necessitating additional cell adhesion enhancements. Their mechanical properties, comparable to natural muscle tissue, and compatibility with high-temperature sterilization processes, underscore their potential as innovative solutions in the field of cultivated meat production.

Multilayered Shape-Morphing Scaffolds with a Hierarchical Structure for Uterine Tissue Regeneration.

Owing to dysfunction of the uterus, millions of couples around the world suffer from infertility. Different from conventional treatments, tissue engineering provides a new and promising approach to deal with difficult problems such as human tissue or organ failure. Adopting scaffold-based tissue engineering, three-dimensional (3D) porous scaffolds in combination with stem cells and appropriate biomolecules may be constructed for uterine tissue regeneration. In this study, a hierarchical tissue engineering scaffold, which mimicked the uterine tissue structure and functions, was designed, and the biomimicking scaffolds were then successfully fabricated using solvent casting, layer-by-layer assembly, and 3D bioprinting techniques. For the multilayered, hierarchical structured scaffolds, poly(l-lactide-co-trimethylene carbonate) (PLLA-co-TMC, "PLATMC" in short) and poly(lactic acid-co-glycolic acid) (PLGA) blends were first used to fabricate the shape-morphing layer of the scaffolds, which was to mimic the function of myometrium in uterine tissue. The PLATMC/PLGA polymer blend scaffolds were highly stretchable. Subsequently, after etching of the PLATMC/PLGA surface and employing estradiol (E2), polydopamine (PDA), and hyaluronic acid (HA), PDA@E2/HA multilayer films were formed on PLATMC/PLGA scaffolds to build an intelligent delivery platform to enable controlled and sustained release of E2. The PDA@E2/HA multilayer films also improved the biological performance of the scaffold. Finally, a layer of bone marrow-derived mesenchymal stem cell (BMSC)-laden hydrogel [which was a blend of gelatin methacryloyl (GelMA) and gelatin (Gel)] was 3D printed on the PDA@E2/HA multilayer films of the scaffold, thereby completing the construction of the hierarchical scaffold. BMSCs in the GelMA/Gel hydrogel layer exhibited excellent cell viability and could spread and be released eventually upon biodegradation of the GelMA/Gel hydrogel. It was shown that the hierarchically structured scaffolds could evolve from the initial flat shape into the tubular structure completely in an aqueous environment at 37 °C, fulfilling the requirement for curved scaffolds for uterine tissue engineering. The biomimicking scaffolds with a hierarchical structure and curved shape, high stretchability, and controlled and sustained E2 release appear to be very promising for uterine tissue regeneration.

Structural descriptor and surrogate modeling for design of biodegradable scaffolds

Biodegradable scaffolds are important to regenerative medicine in that they provide an amicable environment for tissue regrowth. However, establishing structure-property (SP) relationships for scaffold design is challenging due to the complexity of the three-dimensional porous scaffold geometry. The complexity requires high-dimensional geometric descriptors. The training of such a SP surrogate model will need a large amount of experimental or simulation data. In this work, a schema of constructing SP relationship surrogates is developed to predict the degraded mechanical properties from the initial scaffold geometry. A new structure descriptor, the extended surfacelet transform (EST), is proposed to capture important details of pores associated with the degradation of scaffolds. The efficiency is further enhanced with principal component analysis to reduce the high-dimensional EST data into a low-dimensional representation. The schema also includes a kinetic Monte Carlo biodegradation model to simulate the biodegradation of polymer scaffolds and to generate the training data for the formation of SP relationships. The schema is demonstrated with the design of polycaprolactone biodegradable scaffolds by connecting the initial scaffold geometry to the degraded compressive modulus.

A biomimetic three-dimensional porous scaffold of mineralized recombinant collagen-sodium alginate for efficiently repairing critical-size cranial defects

The reconstruction of critical-size bone defects caused by trauma, tumor resection, and congenital anomalies remains a fundamental challenge in tissue engineering. Biomimetic scaffolds have received extensive attention for the discovery of advanced artificial bone substitutes due to their inherent biocompatibility and biodegradability. Herein, we have for the first time developed a biomimetic three-dimensional porous scaffold of mineralized recombinant collagen-sodium alginate (MRCSA) with supreme healing efficacy for critical-size cranial defects. In situ biomineralization using recombinant collagen as the unique biotemplate results in the formation of nano-hydroxyapatite with well-ordered mineralized recombinant collagen with fibrous morphology. The MRCSA scaffold finely mimics the organic-inorganic composition and the uniform porous nanostructures of natural bone, which exhibits excellent biocompatibility, adequate biodegradability, superior cellular activity, and exceptional osteogenic differentiation capability. Magnetic resonance imaging (MRI), Micro-computed tomography (micro-CT), and histological characterization of rat models of critical-size cranial defects have consistently demonstrated that the MRCSA scaffold has regenerated an abundance of new bones to refill the defect sites with much higher bone mineral density, bone volume/total volume as well as trabeculae. The novel biomimetic scaffold provides a remarkably improved remedy of critical-size cranial defects, suggesting very promising applications in orthopedics and plastics.

Consolidation of Spray-Dried Amorphous Calcium Phosphate by Ultrafast Compression: Chemical and Structural Overview.

A large amount of research in orthopedic and maxillofacial domains is dedicated to the development of bioactive 3D scaffolds. This includes the search for highly resorbable compounds, capable of triggering cell activity and favoring bone regeneration. Considering the phosphocalcic nature of bone mineral, these aims can be achieved by the choice of amorphous calcium phosphates (ACPs). Because of their metastable property, these compounds are however to-date seldom used in bulk form. In this work, we used a non-conventional "cold sintering" approach based on ultrafast low-pressure RT compaction to successfully consolidate ACP pellets while preserving their amorphous nature (XRD). Complementary spectroscopic analyses (FTIR, Raman, solid-state NMR) and thermal analyses showed that the starting powder underwent slight physicochemical modifications, with a partial loss of water and local change in the HPO42- ion environment. The creation of an open porous structure, which is especially adapted for non-load bearing bone defects, was also observed. Moreover, the pellets obtained exhibited sufficient mechanical resistance allowing for manipulation, surgical placement and eventual cutting/reshaping in the operation room. Three-dimensional porous scaffolds of cold-sintered reactive ACP, fabricated through this low-energy, ultrafast consolidation process, show promise toward the development of highly bioactive and tailorable biomaterials for bone regeneration, also permitting combinations with various thermosensitive drugs.

ASSESSMENT OF MECHANICAL RESPONSES BETWEEN TRABECULAR BONES AND POROUS SCAFFOLDS UNDER STATIC LOADING AND FLUID FLOW CONDITIONS: A MULTISCALE APPROACH

A three-dimensional porous scaffold is one of the standard and evocative approaches to create a favorable biomechanical environment in tissue engineering for tissue regeneration and repair. The architectural design parameters (e.g., pore-shape, size, distribution and interconnectivity; permeability; specific surface area; etc.) of the porous model have significant influence on their mechano-biological behavior. Along with this, interstitial fluid flow dynamics within the porous scaffold also regulate cell behavior. Therefore, von Mises stress, deformation, wall shear stress, and permeability across the model have been investigated. In this work, a multiscale approach has been applied to explore the various mechanical stimuli that control the cell mechanobiology within a scaffold and compare it to the natural bone with different porosity to identify which architectural design of the scaffold is close to the bone.

3D printed bioactive calcium silicate ceramics as antibacterial scaffolds for hard tissue engineering

VAT photopolymerization technology was applied to fabricate three-dimensional (3D) porous β-Ca2SiO4 ceramic scaffolds functionalized with graphene oxide (GO) sheets decorated with silver nanoparticles (AgNPs).

Chitosan/PVA reinforced boron/strontium multi-substituted hydroxyapatite-based biocomposites: Effects of synthesis pH and coating on the physicochemical, mechanical, and in vitro biological properties of scaffolds

Bioceramics are used in hard tissue applications to repair and replace damaged parts inside the human body. Hydroxyapatite (HAp) is the most widely used bioceramic due to its ability to bind to hard tissues. Furthermore, enhancing the bioactivity of HAp in hard tissue applications through co-substituted particles is of great interest. In this study, different types of HAp microparticles, including unsubstituted, boron-substituted (B-HAp), strontium-substituted (Sr-HAp), boron and strontium co-substituted HAp (B–Sr-HAp) were synthesized at pH 9 and 11 using the wet precipitation method. The impact of synthesis pH on the chemical composition and crystalline structure of the microparticles was investigated. Sintered porous three-dimensional ceramic scaffolds were prepared, polyvinyl alcohol (PVA) and chitosan (Chi) were chosen to improve the mechanical properties of the ceramic scaffolds owing to their biocompatibility and functional groups. In vitro cytotoxicity and in vitro hemocompatibility studies were conducted to evaluate the biocompatibility of the constructs. The results revealed that synthesis pH of 11 yielded the highest substitution without altering the crystalline phase. Also, the PVA/Chi coating improved the compressive strength of all scaffolds, with the most significant improvement observed in Br-HAp due to borate-diol complexation at the ceramic-polymer interface. Preliminary in vitro studies revealed that scaffolds were non-cytotoxic and hemocompatible.