Physical and mechanical properties of a poly-3-hydroxybutyrate-coated nanocrystalline hydroxyapatite scaffold for bone tissue engineering

A major challenge for tissue engineers is the design of scaffolds with appropriate physical and mechanical properties. The present research discusses the formation of ceramic scaffolding in tissue engineering. Hydroxyapatite (HAp) powder was made from bovine bone by thermal treatment at 900?°C; 40, 50 and 60%wt porous HAp was then produced using the polyurethane sponge replication method. Scaffolds were coated with poly-3-hydroxybutyrate (P3HB) for 30?s and 1?min in order to increase the scaffold??s mechanical properties. XRD, SEM and FT-IR were used to study phase structure, morphology and agent groups, respectively. In XRD and FT-IR data, established hydrogen bands between polymer and ceramic matrix confirm that the scaffold is formed as a composite. The scaffold obtained with 50%wt HAp and a 30?s coating was 90% porous, with an average diameter of 100?C400???m, and demonstrated a compressive strength and modulus of 1.46 and 21.27?MPa, respectively. Based on these results, this scaffold is optimised for the aforementioned properties and can be utilised in bone tissue engineering.     

Three-dimensional silk impregnated HAp/PHBV nanofibrous scaffolds for bone regeneration

Three-dimensional silk fibroin impregnated poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibrous scaffolds with or without hydroxyapatite (HAp) were prepared by wet-electrospinning method followed by freeze-drying. Scaffolds with cotton wool-like structure have the average fiber diameter of 450–850?nm with 80–85% porosity. In-vitro cell culture tests using MG-63 osteosarcoma human cells revealed improved cell viability, alkaline phosphatase (ALP) activity and total cellular protein amount on the silk impregnated scaffolds compared to PHBV and HAp/PHBV scaffolds after 10 days of cell culture. Immunohistochemical analyses on the silk impregnated scaffolds showed that HAp triggered cell penetration and type I collagen production. Besides, HAp mineralization tendency increased with a decrease in percent crystallinity of the scaffolds comprising HAp and silk after 4 weeks of incubation in simulated body fluid. Consequently, cotton wool-like HAp/PHBV-SF scaffold would be a promising candidate as a bone-filling material for tissue regeneration.     

Development of bone scaffold using Puntius conchonius fish scale derived hydroxyapatite: Physico-mechanical and bioactivity evaluations

Naturally derived Hydroxyapatite (HAp) from fish scale is finding wide applications in the development of bone scaffold to promote bone regeneration. But porous HAp scaffold is fragile in nature making it unsuitable for bone repair or replacement applications. Thus, it is essential to improve the mechanical property of HAp scaffolds while retaining the interconnected porous structure for tissue ingrowth in vivo. In this study solvent casting particulate leaching technique is used to develop novel Puntius conchonius fish scale derived HAp bone scaffold by varying the wt.% of the HAp from 60 to 80% in PMMA matrix. Physico-chemical, mechanical, structural and bioactive properties of the developed scaffolds are investigated. The obtained results indicate that HAp-PMMA scaffold at 70?wt % HAp loading shows optimal properties with 7.26?±?0.45?MPa compressive strength, 75?±?0.8% porosity, 8.0?±?0.68% degradation and 190?±?11% water absorption. The obtained results of the scaffold can meet the physiological demands to guide bone regeneration. Moreover, in vitro bioactivity analysis also confirms the formation of bone like apatite in the scaffold surface after 28 days of SBF immersion. Thus, the developed scaffold has the potential to be effectively used in bone tissue engineering applications.     

Effect of Morphological Characteristics and Biomineralization of 3D-Printed Gelatin/Hyaluronic Acid/Hydroxyapatite Composite Scaffolds on Bone Tissue Regeneration

The use of porous three-dimensional (3D) composite scaffolds has attracted great attention in bone tissue engineering applications because they closely simulate the major features of the natural extracellular matrix (ECM) of bone. This study aimed to prepare biomimetic composite scaffolds via a simple 3D printing of gelatin/hyaluronic acid (HA)/hydroxyapatite (HAp) and subsequent biomineralization for improved bone tissue regeneration. The resulting scaffolds exhibited uniform structure and homogeneous pore distribution. In addition, the microstructures of the composite scaffolds showed an ECM-mimetic structure with a wrinkled internal surface and a porous hierarchical architecture. The results of bioactivity assays proved that the morphological characteristics and biomineralization of the composite scaffolds influenced cell proliferation and osteogenic differentiation. In particular, the biomineralized gelatin/HA/HAp composite scaffolds with double-layer staggered orthogonal (GEHA20-ZZS) and double-layer alternative structure (GEHA20-45S) showed higher bioactivity than other scaffolds. According to these results, biomineralization has a great influence on the biological activity of cells. Hence, the biomineralized composite scaffolds can be used as new bone scaffolds in bone regeneration.     

Glutaraldehyde crosslinked gelatin/hydroxyapatite nanocomposite scaffold,engineered via compound techniques

In this study, a scaffold was designed to be used in bone tissue repair and the effect of glutaraldehyde (GA) concentration as crosslinking agent was investigated. To mimic the mineral and organic component of natural bone, hydroxyapatite (HAp) and gelatin (GEL) were used as the main components of this composite. Nanopowders of HAp were synthesized and also used together with GEL to engineer a three‐dimensional nanocomposite scaffold. The results show that GEL/HAp nanocomposite is porous with three‐dimensional interconnected structure, pore sizes ranging from 300 to 500 μm, and about 85% porosity. In addition, increasing GA concentration provokes the enhancement of compressive strength until 1 w/v% GA solution followed by a reduction to 2.5%, whereas it causes work fracture to decrease. It was concluded that optimum concentration for crosslinking GEL matrix for this purpose is 1 w/v% GA solution. A specific combination of commonly used techniques applied to engineer a scaffold with almost ideal properties intended for the bone tissue engineering is introduced. In addition, scaffolds that are prepared via this compound process has the potential to be used in the solid free form applications and so being formed in any dimension and geometry relevant to the defect size and shape. POLYM. COMPOS., 31:2112–2120, 2010. © 2010 Society of Plastics Engineers     

Effect of particle size and freezing conditions on freeze-casted scaffold

Freeze casting is one of the emerging and novel manufacturing routes to fabricate porous scaffolds for various applications including orthopedic implants, drug delivery, energy storing devices etc. Thus, it becomes important to understand this process in a deeper sense. Present work was focused to study the effect/influence of basic parameters, particle sizes, and freezing conditions on the mechanical properties and microstructures of porous scaffold fabricated by freeze casting. β-tricalcium phosphate (β-TCP) and hydroxyapatite (HAp) powder with particle sizes of 10?μm and 20?nm were used. Prepared slurries were freeze casted at constant freezing temperature (5?°C) and constant freezing rate (1.86?°C/min) to study the effect of freezing conditions on mechanical and microstructural properties of the porous scaffold. It was observed that porous scaffold fabricated by nanoparticles has given better porosity (63.22–76.16%), than scaffold fabricated by microparticles (13–43.05%) at given solid loading of both freezing conditions. Although, the range of pore size of the scaffold fabricated by nanoparticles (CFR: 2.60–0.84?μm; CFT: 1.66–0.46?μm) was lower than that of scaffold fabricated by microparticles (CFR: 9.45–4.83?μm; CFT: 4.72–2.84?μm). The compressive strength of scaffolds prepared by nanoparticles was in the range of trabecular bone. Moreover, the results of present work will pave the way for the fabrication of porous scaffold with desired pore size and porosity for various implants, energy, and drug delivery applications.     

Preparation and characterization of collagen/silica composite scaffolds for peripheral nerve regeneration

To improve the regeneration of peripheral nerve system, the silica nanoparticles of various concentrations were synthesized in collagen solution and formed to silica incorporated porous collagen structures. We examined various properties such as morphology, chemical composition, wettability, porosity, swelling ratio and degradation behavior of the composite scaffolds. Schwann cells culture was used to evaluate the effect of the collagen/silica composite materials on nerve regeneration. And the content of DNA in Schwann cells was measured. We ascertained that the silica nanoparticles could be incorporated into collagen scaffolds successfully. The incorporation of silica nanoparticles could increase the hydrophobicity, decrease porosity, swelling ratio and degradation rate of the collagen scaffolds. Further, the attachment and proliferation of Schwann cells on the silica incorporated porous collagen patch was much better than that of the collagen patch as control. The number and DNA contents of the cells on the composite scaffolds increased firstly and then decreased with the increment of nanoparticles concentration. It was optimal to combine silica of 25 μg/mL for achieving best cell attachment and proliferation with the highest DNA contents compared with other samples. These results indicate that silica incorporated porous collagen patch may be potentially used as implanted scaffold materials for the peripheral nerve regeneration.     

The effect of filler content on mechanical properties and cell response of elastomeric PGS/apatite foam scaffolds

Poly(glycerol sebacate) (PGS) is a novel polymeric material intended for applications in tissue engineering (TE). This study involves synthesizing the PGS prepolymer (pPGS) and subsequent manufacturing of porous PGS-based scaffolds with an addition of hydroxyapatite (HAp) by means of thermally induced phase separation followed by thermal cross-linking and salt-leaching (TIPS-TCL-SL). The study aims to investigate the effect of the apatite filler content on properties and morphology of porous PGS/HAp scaffolds. The emphasis is put on the mechanical behavior of the material characterized by means of compression tests and dynamic thermal mechanical analysis (DMTA). In addition to the reference polymer scaffold, the composites with filler contents of 10, 20 and 30 wt% have been examined. Our research revealed that the HAp content does not affect the mechanical properties in a directly proportional manner. The 30 wt% addition of HAp resulted in frayed structure and decrease in the mechanical parameters in comparison to other tested specimens. On the other hand, an addition of 10% did not sufficiently boost the properties. Therefore, a 20% addition of HAp was concluded to have superior mechanical properties in comparison to other analyzed specimens. A similar relationship results from the DMTA studies. Moreover, the strain sweep and frequency sweep tests confirmed the stability of the mechanical parameters in various conditions, as well as the elastomeric nature of the materials. Finally, the material did not exhibit cytotoxicity against standard L929 fibroblasts and cells readily populated the scaffolds.     

PGS/HAp Microporous Composite Scaffold Obtained in the TIPS-TCL-SL Method: An Innovation for Bone Tissue Engineering

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (¹H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1β, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.     

Extrusion-based 3D printing of gelatin methacryloyl with nanocrystalline hydroxyapatite

The particle shape and size distribution of inorganic fillers play a crucial role in the scaffold buildability when those are incorporated in the viscoelastic polymers. In order to address this issue, the phase pure rod-shaped nanocrystalline hydroxyapatite (HAp) powders with varying particle sizes and shapes were synthesized by a one-pot hydrothermal method without any regulatory surfactant at an initial solution pH of 9. As-synthesized nanocrystalline HAp particles (0–5 wt%) were incorporated into 15 wt% pre-cross-linked gelatin methacryloyl (GelMA) hydrogel matrix to fabricate a predesigned scaffold architecture using a custom-made 3D bioprinter. The printing parameters (nozzle diameter, extrusion pressure, and printing speed) were optimized for each composition. The biophysical properties (uniaxial compression behavior, swelling ratio, and in vitro degradation) of the composite hydrogel scaffolds were critically analyzed to unravel the role of nano-sized HAp addition. The compression strength and modulus were substantially improved, while the rate of water uptake and bio-enzymatic degradation significantly reduced with HAp content. We propose that the inorganic–organic nanocomposite hydrogel could be efficiently assembled to formulate a potential bioink for 3D bioprinting applications toward tissue regeneration.     

Preparation of a hemiporous hydroxyapatite scaffold and evaluation as a cell-mediated bone substitute

A hemiporous hydroxyapatite (HAp) scaffold was prepared to support the tissue engineered approach to the restoration of damaged bone. The scaffold comprised a porous cell-seeded part and a non-porous load bearing part. A wet processing technique of HAp suspensions was used to shape the hemiporous body. The structure of the porous part was tailored using a stack of heat treated porogen placed on the plaster. The prepared specimen had approximately 30 layers of connected pores, which could accommodate sufficient human bone marrow stromal cells (hBMSCs). The result of an in vitro test showed that hBMSCs successfully proliferated and produced extracellular matrices even at the pore in the deep portion of the scaffolds. The in vivo test in the distal femur of a rabbit showed the formation of new fibrous tissue and tubular vessels with red blood cells in the hBMSCs-seeded scaffold from the pores at the deepest portion as well as from the pore at the periphery of the scaffold. The result was in distinct contrast with the scaffold without cell loading. The preloading of cell was thus very effective in the migration of cells in spite of the unconfirmed connectivity among pores. The present casting approach had the merits of simplicity and versatility in tailoring the scaffold structure without an elaborate device.     

Air‐dried 3D‐collagen–chitosan biocomposite scaffold for tissue engineering application

Collagen–chitosan scaffolds of different compositions were developed using emulsion air‐drying method. The scaffolds prepared adding 10–30 wt% of chitosan to collagen improved the mechanical properties of the composite scaffold, and 7:3 ratio (collagen :chitosan) was found to be a better composite having a tensile strength of 13.57 MPa with 9% elongation at break. The water‐uptake characteristics were performed at different pH and found to be ameliorated for the composite scaffolds compared to pure collagen and chitosan scaffold, respectively. The pores ranging from 100 to 300 μm were well interconnected, and their distribution was fairly homogeneous in the scaffold as observed through scanning electron microscopy. Furthermore, the scaffold decreased the bacterial counts and supported fibroblasts attachment and proliferation, thus demonstrating this composite to be a good substrate for biomedical application.POLYM. COMPOS., 33:2029–2035, 2012. © 2012 Society of Plastics Engineers     

Improvement of mechanical properties and in vitro bioactivity of freeze-dried gelatin/chitosan scaffolds by functionalized carbon nanotubes

Functionalized multiwall carbon nanotubes (f-MWCNTs) were used to reinforce the freeze-dried gelatin (G)/chitosan (Ch) scaffolds for bone graft substitution. Two types of G/Ch scaffolds at a ratio of 2:1 and 3:1 by weight incorporated with 0.025, 0.05, or 0.1 and 0.2 or 0.4?wt% f-MWCNT, respectively, were prepared by freeze drying, and their structure, morphology, and physicochemical and compressive mechanical properties were evaluated. The scaffolds exhibited porous structure with pore size of 80–300 and 120–140?µm for the reinforced scaffolds of G/Ch 2:1 and 3:1, respectively, and porosity 90–93% which slightly decreased with an increase in f-MWCNTs content for both types. Incorporation of f-MWCNTs led to 11- and 9.6-fold increase in modulus, with respect to their pure biopolymer blend scaffolds at a level of 0.05?wt% for G/Ch 2:1 and 0.2?wt% for G/Ch 3:1, respectively. The higher content of f-MWCNTs resulted in loss of mechanical properties due to agglomeration. The highest value of compressive strength and modulus was obtained for G/Ch 2:1 with 0.05?wt% f-MWCNT as 411?kPa and 18.7?MPa, respectively. Improvement of in vitro bioactivity as a result of f-MWCNTs incorporation was proved by formation of a bone-like apatite layer on the surface of scaffolds upon immersion in simulated body fluid. The findings indicate that the f-MWCNT-reinforced gelatin/chitosan scaffolds may be a suitable candidate for bone tissue engineering.     

Fabrication of Hydroxyapatite with Bioglass Nanocomposite for Human Wharton’s-Jelly-Derived Mesenchymal Stem Cell Growing Substrate

Recently, composite scaffolding has found many applications in hard tissue engineering due to a number of desirable features. In this present study, hydroxyapatite/bioglass (HAp/BG) nanocomposite scaffolds were prepared in different ratios using a hydrothermal approach. The aim of this research was to evaluate the adhesion, growth, viability, and osteoblast differentiation behavior of human Wharton’s-jelly-derived mesenchymal stem cells (hWJMSCs) on HAp/BG in vitro as a scaffold for application in bone tissue engineering. Particle size and morphology were investigated by TEM and bioactivity was assessed and proven using SEM analysis with hWJMSCs in contact with the HAp/BG nanocomposite. Viability was evaluated using PrestoBlue^TM assay and early osteoblast differentiation and mineralization behaviors were investigated by ALP activity and EDX analysis simultaneously. TEM results showed that the prepared HAp/BG nanocomposite had dimensions of less than 40 nm. The morphology of hWJMSCs showed a fibroblast-like shape, with a clear filopodia structure. The viability of hWJMSCs was highest for the HAp/BG nanocomposite with a 70:30 ratio of HAp to BG (HAp70/BG30). The in vitro biological results confirmed that HAp/BG composite was not cytotoxic. It was also observed that the biological performance of HAp70/BG30 was higher than HAp scaffold alone. In summary, HAp/BG scaffold combined with mesenchymal stem cells showed significant potential for bone repair applications in tissue engineering.     

Preparation and characterization of Chitosan and PLGA‐based scaffolds for tissue engineering applications

Three dimensional (3D) biodegradable porous scaffolds play a crucial role in bone tissue repair. In this study, four types of 3D polymer/hydroxyapatite (HAp) composite scaffolds were prepared by freeze drying technique in order to mimic the organic/inorganic nature of the bone. Chitosan (CH) and poly(lactic acid‐co‐glycolic acid) (PLGA) were used as the polymeric part and HAp as the inorganic component. Properties of the resultant scaffolds, such as morphology, porosity, degradation, water uptake, mechanical and thermal stabilities were examined. 3D scaffolds having interconnected macroporous structure and 77–89% porosity were produced. The pore diameters were in the range of 6 and 200 µm. PLGA and HAp containing scaffolds had the highest compressive modulus. PLGA maintained the strength by decreasing water uptake but increased the degradation rate. Scaffolds seeded with SaOs‐2 osteoblast cells showed that all scaffolds were capable of encouraging cell adhesion and proliferation. The presence of HAp particles caused an increase in cell number on CH‐HAp scaffolds compared to CH scaffolds, while cell number decreased when PLGA was incorporated in the structure. CH‐PLGA scaffolds showed highest cell number on days 7 and 14 compared to others. Based on the properties such as interconnected porosity, high mechanical strength, and in vitro cell proliferation, blend scaffolds have the potential to be applied in hard tissue treatments. POLYM. COMPOS., 36:1917–1930, 2015. © 2014 Society of Plastics Engineers     

Mechanical and biological performance of rainbow trout collagen-boron nitride nanocomposite scaffolds for soft tissue engineering

We aim to investigate the potential of collagen extracted from rainbow trout for tissue engineering applications. In this regard, nanocomposite scaffolds based on the extracted collagen reinforced with various concentrations of boron nitride (BN) nanoparticles (0, 3, 6, 9, and 12 wt%) were developed. In addition, the role of various concentrations of BN nanoparticles and two-step cross-linking process on the physical and chemical properties of nanocomposite scaffolds were investigated. Our results demonstrated the isolation of Type I collagen with excellent thermal stability but with some structural and chemical differences compared to other sources. The synergic role of BN nanoparticles and two-step cross-linking process resulted in a noticeable improvement in the mechanical properties of collagen-BN scaffolds. Noticeably, incorporation of 6 wt% BN along with a two-step cross-linking process significantly increased the compressive strength (9.5 times) and elastic modulus (four times) of the collagen scaffold. Besides, nanocomposite scaffolds significantly improved proliferation and spreading of MG-63 cell line, confirming their biocompatibility. The results suggested that the incorporation of BN nanoparticles along with a two-step cross-linking process not only could promote the mechanical and thermal performances of collagen scaffolds, but also enhanced high cell viability, and proliferation supporting their potential in tissue engineering applications.     

Fabrication of MgAl2O4 Spinel Scaffolds and Sonochemical Synthesis and Deposition of Hydroxyapatite Nanorods

Hydroxyapatite (HAp) is one of the most emerging biocompatible ceramic widely used as scaffolds in various biomedical applications such as orthopedics and dentistry. In spite of the superior properties for biomedical applications, they exhibit poor mechanical properties. This has lead to the concept of fabricating composite out of bioactive and bioinert material to derive bioactivity in combination with desirable mechanical properties. In this study, bioinert magnesium aluminate (MgAl₂O₄) spinel scaffolds are prepared through polymeric foam replication process followed by sintering. Sintered foams have exhibited good structural integrity and the stress–strain curves recorded during the uniaxial compression have shown a plateau indicating high‐energy absorption capability. Sonochemical process has been employed for the simultaneous synthesis and deposition of HAp formulation from the stoichiometric solution of precursors on the spinel scaffolds. Sonochemical process has resulted in the formation of phase pure HAp with unique morphology of nanorods coated throughout the three‐dimensional foam structures. Cytotoxicity evaluation of this new scaffold material has not shown any alteration in the viability, growth, and morphology of the cells. The new scaffold material thus developed is expected to have high potential for biomedical applications.     

Effect of ZnO reinforcement on the compressive properties,in vitro bioactivity,biodegradability and cytocompatibility of bone scaffold developed from bovine bone-derived HAp and PMMA

In this study, the effect of zinc oxide (ZnO) incorporation on the properties of Hydroxyapatite (HAp)/Poly(methyl methacrylate) (PMMA)/ZnO based composite bone scaffold is investigated. HAp is derived from calcination of bovine bone bio-waste and ZnO is synthesized by direct precipitation technique. Porous scaffolds are developed by gas foaming process using ammonium bicarbonate as the foaming agent and adding ZnO nanoparticles (NPs) at 2.5, 5, 7.5 and 10% (w/w) respectively. Incorporation of ZnO up to 5% (w/w) is found to significantly enhance the porosity, compressive strength, thermal stability and swelling properties of the developed scaffolds. In-vitro bioactivity and biodegradability assessment using simulated body fluid (SBF) show improved results of 5% ZnO loaded scaffolds. Furthermore, the composite scaffold show enhanced cytocompatibility during the in vitro cytotoxicity test performed using XTT assay. A comprehensive study on the scaffold properties shows that 5% ZnO composite scaffold exhibits the best-optimized properties suitable for bone tissue engineering applications.     

Fabrication of polylactic acid/polyethylene glycol (PLA/PEG) porous scaffold by supercritical CO2 foaming and particle leaching

PLA/PEG/NaCl blends were melt‐blended followed by gas foaming and particle leaching process to fabricate porous scaffold with high porosity and interconnectivity. A home‐made triple‐screw compounding extruder was used to intensify the mixability and dispersion of NaCl and PEG in the PLA matrix. Supercritical carbon dioxide was used as physical blowing agent for the microcellular foaming process. Sodium chloride (NaCl) was used as the porogen to further improve the porosity of PLA scaffold. This study investigated the effects of PEG and NaCl on the structure and properties of the PLA‐based blend, as well as the porosity, pore size, interconnectivity, and hydrophilicity of porous scaffolds. It was found that the incorporation of PEG and NaCl significantly improved the crystallization rate and reduced viscoelasticity of PLA. Moreover, scaffolds obtained from PLA/PEG/NaCl blends had an interconnected bimodal porous structure with the open‐pore content about 86% and the highest porosity of 80%. And the presence of PEG in PLA/NaCl composite improved the extraction ability of NaCl particles during leaching process, which resulted in a well‐interconnected structure. The biocompatibility of the porous scaffolds fabricated was verified by culturing fibroblast cells for 10 days. POLYM. ENG. SCI., 55:1339–1348, 2015. © 2015 Society of Plastics Engineers     

Rapid microwave-assisted synthesis of gold loaded hydroxyapatite collagen nano-bio materials for drug delivery and tissue engineering application

A rapid microwave assisted facile synthetic technique was adopted to load gold nanoparticles (Au) on hydroxyapatite (HAp) surface. HAp nanoparticles were primarily synthesized by wet precipitation technique and further used for gold loading and successive collagen coating for biomedical applications. The microwave-assisted controlled synthesis technique with three heating cycles allows the very fast growing of Au seeds over HAp facets. Different sophisticated analytical techniques and spectroscopic characterization were employed to confirm the structural, chemical, and morphological features. The synthesized different concentration “Au” loaded hetero nanostructures coated with collagen (Au–HAp–Col) optimized for drug (Doxorubicin: DOX) loading and releasing purposes for biomedical applications. The maximum drug-loading efficiency of ~58.22% and a pH responsive releasing of ~53% (at pH 4.5) was obtained for 0.1?wt% Au–HAp–Col nanoparticles. To study the cytotoxic effects from the hetero nanostructures, MG-63 osteoblast-like cells were exposed to different concentration ranges on Au–HAp, Au–HAp–Col, and DOX loaded Au–HAp–Col nanoparticles. The non-toxic and bioactive properties of the synthesized nanoparticle-fabricated scaffold promotes cellular attachment, growth, and proliferation. These results indicated that optimized Au–HAp–Col nanoparticles may be promising drug delivery and scaffold materials for multifunctional biomedical applications.