Engineering 2D Mesoporous Silica@MXene‐Integrated 3D‐Printing Scaffolds for Combinatory Osteosarcoma Therapy and NO‐Augmented Bone Regeneration

The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb₂C MXene wrapped with S‐nitrosothiol (R? SNO)‐grafted mesoporous silica with 3D‐printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)‐triggered photonic hyperthermia of MXene in the NIR‐II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone‐regeneration bioactivity, augmented by sufficient blood supply triggered by on‐demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.     

Collaborative Design of MgO/FeOx Nanosheets on Titanium: Combining Therapy with Regeneration

The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeO_x nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeO_x double metal oxide demonstrates good peroxidase activity to catalyze H₂O₂, which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeO_x film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.     

2D‐Black‐Phosphorus‐Reinforced 3D‐Printed Scaffolds:A Stepwise Countermeasure for Osteosarcoma

With the ever‐deeper understanding of nano–bio interactions and the development of fabrication methodologies of nanomaterials, various therapeutic platforms based on nanomaterials have been developed for next‐generation oncological applications, such as osteosarcoma therapy. In this work, a black phosphorus (BP) reinforced 3D‐printed scaffold is designed and prepared to provide a feasible countermeasure for the efficient localized treatment of osteosarcoma. The in situ phosphorus‐driven, calcium‐extracted biomineralization of the intra‐scaffold BP nanosheets enables both photothermal ablation of osteosarcoma and the subsequent material‐guided bone regeneration in physiological microenvironment, and in the meantime endows the scaffolds with unique physicochemical properties favoring the whole stepwise therapeutic process. Additionally, a corrugated structure analogous to Haversian canals is found on newborn cranial bone tissue of Sprague–Dawley rats, which may provide much inspiration for the future research of bone‐tissue engineering.     

A novel photothermally controlled multifunctional scaffold for clinical treatment of osteosarcoma and tissue regeneration

After an osteosarcoma excision, recurrence, large bone defects, and soft tissue injury are significant challenges for clinicians. Conventional treatment by implanting bone replacement materials can induce bone regeneration after surgery, but this does not prevent bleeding, promote soft tissue repair, or help destroy the residual tumor cells. We attempted to develop a new multifunctional scaffold, with the clinical goals of facilitating tumor cell death through thermal ablation and promoting osteogenesis. Accordingly, we first investigated the effect of nano-hydroxyapatite/graphene oxide (nHA/GO) composite particles with different proportions on human osteosarcoma cells (HOS), pre-osteoblastic MC3T3-E1 cells, and human bone marrow mesenchymal stem cells (hBMSC) with or without 808-nm near-infrared (NIR) light irradiation. Next, we fabricated a novel temperature-controlled multifunctional nano-hydroxyapatite/graphene oxide/chitosan (nHA/GO/CS) scaffold, which can effectively kill human osteosarcoma cells under 808-nm NIR irradiation by reaching a temperature of 48 °C and further promote osteogenesis of hBMSC at 42 ± 0.5 °C in coordination with nHA. This scaffold demonstrates the best post-operative bone volume/tissue volume (BV/TV) ratio performance (20.36%) 8 weeks after scaffold implantation in the cranial defects of rats. Further exploration has revealed that NIR irradiation may promote the osteogenesis of hBMSC with the addition of nHA by enhancing the BMP2/Smad signaling pathway. Further, this scaffold has a good hemostatic effect and facilitates soft tissue repair under irradiation. This novel photothermally controlled multifunctional scaffold, which not only kills human osteosarcoma cells but also facilitates tissue regeneration, is a promising clinical tool for treating tissue injuries from an osteosarcoma resection.     

掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥的制备与性能表征

骨肉瘤是一种常见的恶性骨肿瘤, 常通过手术切除进行治疗。但术后造成的骨缺损难以自愈, 残余肿瘤细胞还会增加复发可能性。本研究开发了一种用于修复骨缺损和协同治疗骨肉瘤的掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥。首先通过溶胶-凝胶法结合固态反应制备了可作为光热剂和药物载体的掺钕介孔硼硅酸盐生物活性玻璃陶瓷微球(MBGC-xNd), 然后将微球与海藻酸钠(SA)溶液混合制备了可同时进行光热治疗和化学治疗的可注射骨水泥(MBGC-xNd/SA)。结果表明掺Nd³⁺赋予微球可控的光热性能, 负载阿霉素(DOX)的微球显示出持续的药物释放行为。此外, 载药骨水泥的药物释放量随着温度的升高而显著增加, 说明光热疗法产生的热量可促进DOX释放。体外细胞实验结果表明, MBGC-xNd/SA具有良好的促成骨活性, 并且光热-化学联合疗法对MG-63骨肉瘤细胞起到了更显著的杀伤作用, 表现出协同效应。因此,MBGC-xNd/SA作为一种新颖的多功能骨修复材料, 在骨肉瘤的术后治疗方面具有良好的应用前景。     

Hierarchically multifunctional bioactive nanoglass for integrated tumor/infection therapy and impaired wound repair

The complex wound repair induced by tumor surgery and infection is still the clinical challenge due to the subsequent tumor recurrence and serious inflammation. Herein, we develop a bioactive Si-Ca-Sr glass-based therapy-regeneration-enabled nanohybrids (BSr@PPE) with hierarchical versatility for overcoming the challenges of tumor and infection-impaired wound repair. BSr@PPE showed a representative concentration-dependent photothermal effect, strong free radical scavenging and antibacterial ability, as well as good UV-shielding properties and high biocompatibility. BSr@PPE could efficiently kill tumor cells through the photothermal effect, show the robust antibacterial activity against normal and multi-drug resistant bacteria and enhance the fibroblasts migration in vitro. In vivo animal experiments suggested that BSr@PPE could effectively promote epithelial reconstruction, collagen deposition and angiogenesis in normal wounds, reduce inflammation and enhance repair in multi-drug bacterial infected wounds, accelerate the tumor-impaired wound through inhibit the tumor cells. This work may provide a new strategy and multifunctional bioactive material for treating the tissue repair and regeneration under the multi-pathological environments.     

Bioactive borate glass scaffolds: in vitro and in vivo evaluation for use as a drug delivery system in the treatment of bone infection

The objective of this work was to evaluate borate bioactive glass scaffolds (with a composition in the system Na₂O–K₂O–MgO–CaO–B₂O₃–P₂O₅) as devices for the release of the drug Vancomycin in the treatment of bone infection. A solution of ammonium phosphate, with or without dissolved Vancomycin, was used to bond borate glass particles into the shape of pellets. The in vitro degradation of the pellets and their conversion to a hydroxyapatite-type material in a simulated body fluid (SBF) were investigated using weight loss measurements, chemical analysis, X-ray diffraction, and scanning electron microscopy. The results showed that greater than 90% of the glass in the scaffolds degraded within 1 week, to form poorly crystallized hydroxyapatite (HA). Pellets loaded with Vancomycin provided controlled release of the drug over 4 days. Vancomycin-loaded scaffolds were implanted into the right tibiae of rabbits infected with osteomyelitis. The efficacy of the treatment was assessed using microbiological examination and histology. The HA formed in the scaffolds in vivo, resulting from the conversion of the glass, served as structure to support the growth of new bone and blood vessels. The results in this work indicate that bioactive borate glass could provide a promising biodegradable and bioactive material for use as both a drug delivery system and a scaffold for bone repair.     

Polymer-bioceramic composites for tissue engineering scaffolds

Designing tissue engineering scaffolds with the required mechanical properties and favourable microstructure to promote cell attachment, growth and new tissue formation is one of the key challenges facing the tissue engineering field. An important class of scaffolds for bone tissue engineering is based on bioceramics and bioactive glasses, including: hydroxyapatite, bioactive glass (e.g. Bioglass^®), alumina, TiO₂ and calcium phosphates. The primary disadvantage of these materials is their low resistance to fracture under loads and their high brittleness. These drawbacks are exacerbated by the fact that optimal scaffolds must be highly porous (>90% porosity). Several approaches are being explored to enhance the structural integrity, fracture strength and toughness of bioceramic scaffolds. This paper reviews recent proposed approaches based on developing bioactive composites by introducing polymer coatings or by forming interpenetrating polymer-bioceramic microstructures which mimic the composite structure of bone. Several systems are analysed and scaffold fabrication processes, microstructure development and mechanical properties are discussed. The analysis of the literature suggests that the scaffolds reviewed here might represent the optimal solution and be the scaffolds of choice for bone regeneration strategies.     

Black Bioceramics: Combining Regeneration with Therapy

Bioceramics have been developed from bioinert to bioactive or biodegradable materials in the past few decades. However, at present, traditional bioceramics are still mainly used in bone tissue regeneration and dental restoration. In this work, a new generation of “black bioceramics,” extending the applications from tissue regeneration to disease therapy, is presented. Black bioceramics, through magnesium thermal reduction of traditional white ceramics, including silicate-based (e.g., CaSiO₃, MgSiO₃) and phosphate-based (e.g., Ca₃(PO₄)₂, Ca₅(PO₄)₃(OH)), are successfully synthesized. Due to the presence of oxygen vacancies and structural defects, the black bioceramics possess photothermal functionality while maintaining their initial high bioactivity and regenerative capacity. These black bioceramics show excellent photothermal antitumor effects for both skin and bone tumors. At the same time, they have significantly improved bioactivity for skin/bone tissue repair in vitro and in vivo. These fascinating properties award the black bioceramics with profound applications in both tumor therapy and tissue regeneration, which should greatly promote the scientific relevance and clinical application of bioceramics, representing a promising new direction of cell-instructive biomaterials.     

Covalently Grafted Biomimetic Matrix Reconstructs the Regenerative Microenvironment of the Porous Gradient Polycaprolactone Scaffold to Accelerate Bone Remodeling

Integrating a biomimetic extracellular matrix to improve the microenvironment of 3D printing scaffolds is an emerging strategy for bone substitute design. Here, a “soft–hard” bone implant (BM-g-DPCL) consisting of a bioactive matrix chemically integrated on a polydopamine (PDA)-coated porous gradient scaffold by polyphenol groups is constructed. The PDA-coated “hard” scaffolds promoted Ca²⁺ chelation and mineral deposition; the “soft” bioactive matrix is beneficial to the migration, proliferation, and osteogenic differentiation of stem cells in vitro, accelerated endogenous stem cell recruitment, and initiated rapid angiogenesis in vivo. The results of the rabbit cranial defect model (Φ = 10 mm) confirmed that BM-g-DPCL promoted the integration between bone tissue and implant and induced the deposition of bone matrix. Proteomics confirmed that cytokine adhesion, biomineralization, rapid vascularization, and extracellular matrix formation are major factors that accelerate bone defect healing. This strategy of highly chemically bonded soft–hard components guided the construction of the bioactive regenerative scaffold.     

Mild Photothermal-Stimulation Based on Injectable and Photocurable Hydrogels Orchestrates Immunomodulation and Osteogenesis for High-Performance Bone Regeneration

A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.     

Biodegradable and bioactive properties of a novel bone scaffold coated with nanocrystalline bioactive glass for bone tissue engineering

The development of the new technologies of bone tissue engineering requires the production of bioactive and biodegradable macroporous scaffolds. Hydroxyapatite (HA) ceramics are useful bone substitutes, but they degrade minimally. Tricalcium phosphates also show poor ability of Ca-P formation both in-vitro and in-vivo, although they are degradable. The present study introduces a biodegradable, bioactive, and macroporous scaffold with suitable mechanical properties. The prepared hydroxyapatite scaffold was coated with a nanocrystalline bioactive glass layer to be subsequently sintered at different temperatures. The bioactivity and degradability of the coated scaffolds were investigated by standard procedures. The ability to induce Ca-P formation in SBF (simulated body fluid) was also investigated semi-quantitatively. BS1 scaffolds (scaffolds sintered at 800 °C with a holding time of 2 h) showed remarkable bioactivity and degradability simultaneously. Formation of a nanocrystalline phase (Si₂PO₇) during the sintering considerably decreased the capability of BS1 scaffolds for Ca-P formation and the rate of degradation but enhanced their mechanical properties. The BS1 scaffolds showed not only significant bioactivity but also good degradability and suitable mechanical property.     

In vivo evaluation of composites of PLGA and apatite with two different levels of crystallinity

The cortical bone response towards poly(lactide-co-glycolide) (70/30) (PLGA) (70/30)/apatite complex scaffolds with different levels of crystallinity was investigated. Apatite with different levels of crystallinity, Ca-deficient hydroxyapatite (CDHA), which has a low crystallinity, and a mixture of carbonated hydroxyapatite (CHA) and CDHA, which has a higher crystallinity, were prepared from an aqueous mixture of Ca-EDTA complex, H₂O₂, H₃PO₄, and NH₄OH. Two porous PLGA(70/30)/apatite composite scaffolds, composite scaffold A (containing low crystallinity CDHA) and composite scaffold B (containing the higher crystallinity CHA/CDHA mixture), were prepared. Afterwards, pure porous PLGA and the two composite scaffolds were implanted into the cortical bone of rabbit tibiae for 12 weeks. High-resolution microfocus X-ray computed tomography and histological examinations revealed a better bone response for composite scaffold A compared with PLGA and composite scaffold B. For composite scaffold A, the original bone defect was almost filled with new bone. Quantitative analysis revealed that composite scaffold A produced a significantly greater amount of new bone. The present study demonstrated that the level of apatite crystallinity influences bone response. A PLGA/apatite porous composite with a low level of apatite crystallinity shows promise as a bone substitute or scaffold material for bone tissue engineering.     

Assessment of bone regeneration of a tissue-engineered bone complex using human dental pulp stem cells/poly(ε-caprolactone)-biphasic calcium phosphate scaffold constructs in rabbit calvarial defects

The objective of the present study was to investigate the effect of a fabricated combination of poly-?-caprolactone (PCL)–biphasic calcium phosphate (BCP) with the modified melt stretching and multilayer deposition (mMSMD) technique on human dental pulp stem cell (hDPSC) differentiation to be osteogenic like cells for bone regeneration of calvarial defects in rabbit models. hDPSCs extracted from human third molars were seeded onto mMSMD PCL-BCP scaffolds and the osteogenic gene expression was tested prior to implantation in vivo. Two standardized 11?mm in diameter circular calvarial defects were created in 18 adult male New Zealand white rabbits. The rabbits were divided into 4 groups: (1) hDPSCs seeded in mMSMD PCL-BCP scaffolds; (2) mMSMD PCL-BCP scaffolds alone, (3) empty defects and (4) autogenous bone (n?=?3 site/time point/groups). After two, four and eight weeks after the operation, the specimens were harvested for micro-CT including histological and histomorphometric analysis. The explicit results presented an interesting view of the bioengineered constructs of hDPSCs in PCL-BCP scaffolds that increased the newly formed bone compared to the empty defect and scaffold alone groups. The results demonstrated that hDPSCs combined with mMSMD PCL-BCP scaffolds may be an augmentation material for bony defect.     

Static and dynamic cultivation of bone marrow stromal cells on biphasic calcium phosphate scaffolds derived from an indirect rapid prototyping technique

The adequate regeneration of large bone defects is still a major problem in orthopaedic surgery. Synthetic bone substitute materials have to be biocompatible, biodegradable, osteoconductive and processable into macroporous scaffolds tailored to the patient specific defect. Hydroxyapatite (HA) and tricalcium phosphate (TCP) as well as mixtures of both phases, biphasic calcium phosphate ceramics (BCP), meet all these requirements and are considered to be optimal synthetic bone substitute materials. Rapid prototyping (RP) can be applied to manufacture scaffolds, meeting the criteria required to ensure bone ingrowth such as high porosity and defined pore characteristics. Such scaffolds can be used for bone tissue engineering (BTE), a concept based on the cultivation of osteogenic cells on osteoconductive scaffolds. In this study, scaffolds with interconnecting macroporosity were manufactured from HA, TCP and BCP (60 wt% HA) using an indirect rapid prototyping technique involving wax ink-jet printing. ST-2 bone marrow stromal cells (BMSCs) were seeded onto the scaffolds and cultivated for 17 days under either static or dynamic culture conditions and osteogenic stimulation. While cell number within the scaffold pore system decreased in case of static conditions, dynamic cultivation allowed homogeneous cell growth even within deep pores of large (1,440 mm³) scaffolds. Osteogenic cell differentiation was most advanced on BCP scaffolds in both culture systems, while cells cultured under perfusion conditions were generally more differentiated after 17 days. Therefore, scaffolds manufactured from BCP ceramic and seeded with BMSCs using a dynamic culture system are the method of choice for bone tissue engineering.     

3D bioprinting of multicellular scaffolds for osteochondral regeneration

Regeneration of osteochondral tissue is of great potentialities in repairing severe osteochondral defects. However, anisotropic physiological characteristics and tissue linage difference make the regeneration of osteochondral tissue remain a huge challenge. Herein, a multicellular system based on a bilayered co-culture scaffold mimicking osteochondral tissues was successfully developed for an alternative of osteochondral regeneration via a 3D bioprinting strategy. The dual function of integrally repairing both cartilage and bone could be achieved by designing multiple-cells distribution and a cell-induced bioink containing bioceramic particles. As an important bioactive agent, the Li-Mg-Si bioceramics-containing bioink exhibited the function of simultaneously stimulating multiple cells for differentiation towards specific directions. The 3D bioprinted co-culture scaffolds showed the capacity for osteochondral tissue regeneration by inducing osteogenic and chondrogenic differentiation in vitro and accelerating the repair of severe osteochondral defects in vivo. This study offers a potential strategy for complex tissue reconstruction through bioprinting multiple tissue cells in combination of bioceramics-stimulating bioinks.     

Electrospun submicron bioactive glass fibers for bone tissue scaffold

Submicron bioactive glass fibers 70S30C (70 mol% SiO₂, 30 mol% CaO) acting as bone tissue scaffolds were fabricated by electrospinning method. The scaffold is a hierarchical pore network that consists of interconnected fibers with macropores and mesopores. The structure, morphological characterization and mechanical properties of the submicron bioactive glass fibers were studied by XRD, EDS, FIIR, SEM, N₂ gas absorption analyses and nanoindentation. The effect of the voltage on the morphology of electrospun bioactive glass fibers was investigated. It was found that decreasing the applied voltage from 19 to 7 kV can facilitate the formation of finer fibers with fewer bead defects. The hardness and Young’s modulus of submicron bioactive glass fibers were measured as 0.21 and 5.5 GPa, respectively. Comparing with other bone tissue scaffolds measured by nanoindentation, the elastic modulus of the present scaffold was relatively high and close to the bone.     

NIR Light-Driving Barrier-Free Group Rotation in Nanoparticles with an 88.3% Photothermal Conversion Efficiency for Photothermal Therapy

Traditional photothermal therapy requires high-intensity laser excitation for cancer treatments due to the low photothermal conversion efficiency (PCE) of photothermal agents (PTAs). PTAs with ultra-high PCEs can decrease the required excited light intensity, which allows safe and efficient therapy in deep tissues. In this work, a PTA is synthesized with high PCE of 88.3% based on a BODIPY scaffold, by introducing a  CF₃ “barrier-free” rotor on the meso-position (tfm-BDP). In both the ground and excited state, the  CF₃ moiety in tfm-BDP has no energy barrier to rotation, allowing it to efficiently dissipate absorbed (NIR) photons as heat. Importantly, the barrier-free rotation of  CF₃ can be maintained after encapsulating tfm-BDP into polymeric nanoparticles (NPs). Thus, laser irradiation with safe intensity (0.3 W cm⁻², 808 nm) can lead to complete tumor ablation in tumor-bearing mice after intravenous injection of tfm-BDP NPs. This strategy of “barrier-free rotation” provides a new platform for future design of PTT agents for clinical cancer treatment.     

Effect of process parameters on the properties of selective laser sintered Poly(3-hydroxybutyrate) scaffolds for bone tissue engineering

Porous scaffolds are biocompatible and bioactive temporary substrates. They should present appropriated microstructure, mechanical properties and surface properties for guiding bone tissue regeneration. In this work, scaffolds of Poly(3-hydroxybutyrate) (PHB) were printed by Selective Laser Sintering (SLS). The effect of scan spacing (SS) and powder layer thickness (PLT) on the morphology, mechanical properties and dimensional deviations related to the digital model of sintered scaffolds was evaluated. Curling was observed in the first built layers of scaffolds, mainly for scaffolds printed with the lowest PLT. Besides designed pores, the scaffolds also presented micropores derived from the incomplete sinterisation of PHB particles. This morphology can be advantageous for bone regeneration. The variation of PLT caused a higher difference between the values of scaffold mechanical properties than the variation of SS. The scaffolds, except the one printed with the highest PLT or SS, showed mechanical properties within the lower range of human trabecular bone.     

Prolonged release from PLGA/HAp scaffolds containing drug-loaded PLGA/gelatin composite microspheres

Porous scaffolds that can prolong the release of bioactive factors are urgently required in bone tissue engineering. In this study, PLGA/gelatin composite microspheres (PGMs) were carefully designed and prepared by entrapping poly(l-lactide-co-glycolide) (PLGA) microspheres (PMs) in gelatin matrix. By mixing PGMs with PLGA solution directly, drug-loaded PLGA/carbonated hydroxyapatite (HAp)/PGMs composite scaffolds were successfully fabricated. In vitro release of fluorescein isothiocyanate-dextran (FD70S) as a model drug from the scaffolds as well as PMs and PGMs was studied by immersing samples in phosphate buffered saline (pH = 7.4) at 37°C for 32 days. Compared with PMs, PGMs and PLGA/HAp/PGMs scaffolds exhibited slow and steady release behavior with constant release rate and insignificantly original burst release. The swelling of PGMs, diffusion of drugs, and degradation of polymer dominated the release behaviors synergistically. The PLGA/HAp/PGMs scaffold offers a novel option for sequential or simultaneous release of several drugs in terms of bone regeneration.