Stem Cells For Bone Regeneration Research Articles

The Therapeutic Potential of Hematopoietic Stem Cells in Bone Regeneration.

The repair process of bone fractures is a complex biological mechanism requiring the recruitment and in situ functionality of stem/stromal cells from the bone marrow (BM). BM mesenchymal stem/stromal cells have been widely explored in multiple bone tissue engineering applications, whereas the use of hematopoietic stem cells (HSCs) has been poorly investigated in this context. A reasonable explanation is the fact that the role of HSCs and their combined effect with other elements of the hematopoietic niches in the bone-healing process is still elusive. Therefore, in this review we intend to highlight the influence of HSCs in the bone repair process, mainly through the promotion of osteogenesis and angiogenesis at the bone injury site. For that, we briefly describe the main biological characteristics of HSCs, as well as their hematopoietic niches, while reviewing the biomimetic engineered BM niche models. Moreover, we also highlighted the role of HSCs in translational in vivo transplantation or implantation as promoters of bone tissue repair. Impact statement The ability of bone to natural self-heal depends on the size and stabilization level of the tissue fracture, and it is impaired in several pathophysiological conditions. Considering that the available treatment options have demonstrated limited regenerative performance, the hematopoietic stem cells (HSCs) co-cultured in different tissue engineering strategies have emerged as a powerful tool to promote effective bone regeneration and healing. Here, we reviewed the most important biomimetic bone-marrow hematopoietic niches and showed the regenerative potential of these cells, both in vitro and in translational in vivo transplantation/implantation approaches. This knowledge encourages the development of new HSC-related bone regenerative therapies.

The Role of Adipose Stem Cells in Bone Regeneration and Bone Tissue Engineering.

Bone regeneration is a complex process that is influenced by tissue interactions, inflammatory responses, and progenitor cells. Diseases, lifestyle, or multiple trauma can disturb fracture healing, which might result in prolonged healing duration or even failure. The current gold standard therapy in these cases are bone grafts. However, they are associated with several disadvantages, e.g., donor site morbidity and availability of appropriate material. Bone tissue engineering has been proposed as a promising alternative. The success of bone-tissue engineering depends on the administered cells, osteogenic differentiation, and secretome. Different stem cell types offer advantages and drawbacks in this field, while adipose-derived stem or stromal cells (ASCs) are in particular promising. They show high osteogenic potential, osteoinductive ability, and immunomodulation properties. Furthermore, they can be harvested through a noninvasive process in high numbers. ASCs can be induced into osteogenic lineage through bioactive molecules, i.e., growth factors and cytokines. Moreover, their secretome, in particular extracellular vesicles, has been linked to fracture healing. The aim of this review is a comprehensive overview of ASCs for bone regeneration and bone tissue engineering.

Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects

BackgroundExtracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation.MethodsDPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation.ResultsMicro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL.ConclusionsThese results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.

Clinical Efficacy of Mesenchymal Stem Cells in Bone Regeneration in Oral Implantology. Systematic Review and Meta-Analysis.

In bone regeneration, obtaining a vital bone as similar as possible to native bone is sought. This review aimed to evaluate the efficacy of stem cells in maxillary bone regeneration for implant rehabilitation and to review the different techniques for obtaining and processing these cells. A systematic review and meta-analysis were performed using the Pubmed/Medline (NCBI), Cochrane, Scielo, and Scopus databases, without restriction on the publication date. The following Mesh terms were used, combined by the Boolean operator “AND”: “dental implants” AND “stem cells” AND “bioengineering”. Applying inclusion and exclusion criteria, five articles were obtained and three were added after manual search. The results from the meta-analysis (18 patients) did not provide significant differences despite the percentage of bone formed in the maxillary sinus, favoring the stem cell group, and the analysis of the percentage of residual Bio-Oss® showed results favoring the control group. Stem cell regeneration usually shows positive vascular and viable bone formation. In conclusion, using mesenchymal stem cells in bone regeneration provides benefits in the quality of bone, similar or even superior to autologous bone, all this through a minimally invasive procedure.

An injectable and antibacterial calcium phosphate scaffold inhibiting Staphylococcus aureus and supporting stem cells for bone regeneration

Staphylococcus aureus (S. aureus) is the major pathogen for osteomyelitis, which can lead to bone necrosis and destruction. There has been no report on antibacterial calcium phosphate cement (CPC) against S. aureus. The aims of this study were to: (1) develop novel antibacterial CPC-chitosan-alginate microbead scaffold; (2) investigate mechanical and antibacterial properties of CPC-chitosan-penicillin-alginate scaffold; (3) evaluate the encapsulation and delivery of human umbilical cord mesenchymal stem cells (hUCMSCs). Flexural strength, elastic modulus and work-of-fracture of the CPC-chitosan-penicillin-alginate microbeads scaffold and CPC-chitosan scaffold were evaluated. Penicillin release profile and antibacterial effects on S. aureus were determined. The hUCMSC delivery and release from penicillin-alginate microbeads were investigated. Injectable CPC-chitosan-penicillin-alginate microbeads scaffold was developed for the first time. CPC-chitosan-penicillin-alginate microbeads scaffold had a flexural strength of 3.16 ± 0.55 MPa, matching that of cancellous bone. With sustained penicillin release, the new scaffold had strong antibacterial effects on S. aureus, with an inhibition zone diameter of 32.2 ± 2.5 mm, greater than that of penicillin disk control (15.1 ± 2.0 mm) (p < 0.05). Furthermore, this injectable and antibacterial scaffold had no toxic effects, yielding excellent hUCMSC viability, which was similar to that of CPC control without antibacterial activity (p > 0.05). CPC-chitosan-penicillin-microbeads scaffold had injectability, good strength, strong antibacterial effects, and good biocompatibility to support stem cell viability for osteogenesis. CPC-chitosan-penicillin-microbeads scaffold is promising for dental, craniofacial and orthopedic applications to combat infections and promote bone regeneration.

Ultrasmall Superparamagnetic Iron Oxide Labeled Silk Fibroin/Hydroxyapatite Multifunctional Scaffold Loaded With Bone Marrow-Derived Mesenchymal Stem Cells for Bone Regeneration.

Numerous tissue-engineered constructs have been investigated as bone scaffolds in regenerative medicine. However, it remains challenging to non-invasively monitor the biodegradation and remodeling of bone grafts after implantation. Herein, silk fibroin/hydroxyapatite scaffolds incorporated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were successfully synthesized, characterized, and implanted subcutaneously into the back of nude mice. The USPIO labeled scaffolds showed good three-dimensional porous structures and mechanical property, thermal stability for bone repair. After loaded with bone marrow-derived mesenchymal stem cells (BMSCs), the multifunctional scaffolds promoted cell adhesion and growth, and facilitated osteogenesis by showing increased levels of alkaline phosphatase activity and up-regulation of osteoblastic genes. Furthermore, in vivo quantitative magnetic resonance imaging (MRI) results provided valuable information on scaffolds degradation and bone formation simultaneously, which was further confirmed by computed tomography and histological examination. These findings demonstrated that the incorporation of USPIO into BMSCs-loaded multifunctional scaffold system could be feasible to noninvasively monitor bone regeneration by quantitative MRI. This tissue engineering strategy provides a promising tool for translational application of bone defect repair in clinical scenarios.

Osteogenic and angiogenic lineage differentiated adipose-derived stem cells for bone regeneration of calvarial defects in rabbits.

Cell sheet techniques are widely used in bone engineering. However, vascularization remains a challenge in fabricating vascularized engineered bone. The goal of this study was to induce adipose-derived stem cell (ADSC) osteogenic and angiogenic lineage differentiation and investigate the use of bidiretionally differentiated ADSCs for bone regeneration. ADSCs were cultured to form an osteogenic cell sheet. Other ADSCs were induced to differentiate into endothelial progenitor cells (EPCs), which were identified and characterized by morphological observation and CD31 immunofluorescent staining. Then, the ADSC sheet-EPC complexes were implanted subcutaneously into nude mice, while ADSC sheets alone were implanted as a control. After 8 weeks of transplantation, microcomputed tomography (micro-CT) and histological observation were used to assess bone formation. We then implanted the complexes in calvarial defects in rabbits and assessed bone repair by micro-CT and histological analysis. The ADSC sheets consisted of multiple layers of cells and extracellular matrix. The obtained EPCs formed capillary-like structures and expressed the specific antigen marker CD31. The osteogenic ADSC sheet-EPC complexes formed dense and well-vascularized new bone tissue at 8 weeks after implantation. Bone density was significantly lower in the control group than in the complex group (p < .05). In addition, the reconstruction of calvarial defects in rabbits in complex group was obviously greater than that in the control group (p < .05). These results suggested that the approach of engineering bone tissue with bidiretionally differentiated ADSCs enabled bone regeneration, thus offering a promising strategy for repairing bone defects.

Effectiveness of mesenchymal stem cell-conditioned medium in bone regeneration in animal and human models: a systematic review and meta-analysis

BackgroundGiven the limitations of current therapies for the reconstruction of bone defects, regenerative medicine has arisen as a new therapeutic strategy along with mesenchymal stem cells (MSCs), which, because of their osteogenic potential and immunomodulatory properties, have emerged as a promising alternative for the treatment of bone injuries. In vivo studies have demonstrated that MSCs have a positive effect on regeneration due to their secretion of cytokines and growth factors that, when collected in conditioned medium (MSC-CM) and applied to an injured tissue, can modulate and promote the formation of new tissue.ObjectiveTo evaluate the effectiveness of application of conditioned medium derived from mesenchymal stem cells in bone regeneration in animal and human models.MethodsWe conducted a systematic review with a comprehensive search through February of 2018 using several electronic databases (MEDLINE, EMBASE, SCOPUS, CENTRAL (Ovid), and LILACS), and we also used the “snowballing technique”. Articles that met the inclusion criteria were selected through abstract review and subsequent assessment of the full text. We assessed the risk of bias with the SYRCLE and Cochrane tools, and three meta-analyses were performed.ResultsWe included 21 articles, 19 of which used animal models and 2 of which used human models. In animal models, the application of MSC-CM significantly increased the regeneration of bone defects in comparison with control groups. Human studies reported early mineralization in regenerated bones, and no bone resorption, inflammation, nor local or systemic alterations were observed in any case. The meta-analysis showed an overall favorable effect of the application of MSC-CM.ConclusionsThe application of MSC-CM to bone defects has a positive and favorable effect on the repair and regeneration of bone tissue, particularly in animal models. It is necessary to perform additional studies to support the application of MSC-CM in clinical practice.

Current and future uses of skeletal stem cells for bone regeneration.

The postnatal skeleton undergoes growth, modeling, and remodeling. The human skeleton is a composite of diverse tissue types, including bone, cartilage, fat, fibroblasts, nerves, blood vessels, and hematopoietic cells. Fracture nonunion and bone defects are among the most challenging clinical problems in orthopedic trauma. The incidence of nonunion or bone defects following fractures is increasing. Stem and progenitor cells mediate homeostasis and regeneration in postnatal tissue, including bone tissue. As multipotent stem cells, skeletal stem cells (SSCs) have a strong effect on the growth, differentiation, and repair of bone regeneration. In recent years, a number of important studies have characterized the hierarchy, differential potential, and bone formation of SSCs. Here, we describe studies on and applications of SSCs and/or mesenchymal stem cells for bone regeneration.

Role of Adult Tissue-Derived Pluripotent Stem Cells in Bone Regeneration

BackgroundBone marrow-derived mononuclear cells (BM-MNC) consist of a heterogeneous mix of mesenchymal stem cells (MSC), hematopoietic progenitor cells (HPC), endothelial progenitor cells (EPC), monocytes, lymphocytes and pluripotent stem cells. Whereas the importance of MSC and EPC has been well documented in bone healing and regeneration studies, the role of pluripotent stem cells is still poorly understood. In the present study we evaluated if and how Very Small Embryonic Like cells (VSEL), isolated from rat BM-MNC, contribute to bone healing.MethodsLarge bone defects were made in the femurs of 38 Sprague Dawley female rats and treated with β-TCP scaffold granules seeded with male VSEL; BM-MNC, VSEL-depleted BM-MNC or scaffold alone, and bone healing was evaluated at 8 weeks post-surgery.ResultsBone healing was significantly increased in defects treated with VSEL and BM-MNC, compared to defects treated with VSEL-depleted BM-MNC. Donor cells were detected in new bone tissue, in all the defects treated with cells, and in fibrous tissue only in defects treated with VSEL-depleted BM-MNC. The number of CD68+ cells was the highest in the VSEL-depleted group, whereas the number of TRAP positive cells was the lowest in this group.ConclusionsBased on the results, we can conclude that VSEL play a role in BM-MNC induced bone formation. In our rat femur defect model, in defects treated with VSEL-depleted BM-MNC, osteoclastogenesis and bone formation were decreased, and foreign body reaction was increased.

Adult Stem Cells for Bone Regeneration and Repair.

The regeneration of bone fractures, resulting from trauma, osteoporosis or tumors, is a major problem in our super-aging society. Bone regeneration is one of the main topics of concern in regenerative medicine. In recent years, stem cells have been employed in regenerative medicine with interesting results due to their self-renewal and differentiation capacity. Moreover, stem cells are able to secrete bioactive molecules and regulate the behavior of other cells in different host tissues. Bone regeneration process may improve effectively and rapidly when stem cells are used. To this purpose, stem cells are often employed with biomaterials/scaffolds and growth factors to accelerate bone healing at the fracture site. Briefly, this review will describe bone structure and the osteogenic differentiation of stem cells. In addition, the role of mesenchymal stem cells for bone repair/regrowth in the tissue engineering field and their recent progress in clinical applications will be discussed.

Stem Cells for Bone Regeneration: Current State and Future Directions.

Mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes, each of which is important for musculoskeletal tissue regeneration and repair. Reconstruction and healing of bony defects remains a major clinical challenge. Even as surgical practices advance, some severe cases of bone loss do not yield optimal recovery results. New techniques involving implantation of stem cells and tissue-engineered scaffolds are being developed to help improve bone and cartilage repair. The invasiveness and low yield of harvesting MSCs from the bone marrow (BMSCs) has led to the investigation of alternatives, including adipose-derived mesenchymal stem cells (ASCs). A review of the literature yielded several studies concerning the use of BMSCs and ASCs for the treatment of bone defects in both in vitro and in vivo models. Although both ASCs and BMSCs have demonstrated bone regenerative capabilities, BMSCs have outperformed ASCs in vitro. Despite these in vitro study findings, in vivo study results remain variable. Analysis of the literature seems to conclude there is no significant difference between bone regeneration using ASCs or BMSCs in vivo. Improved study design and standardization may enhance the application of these studies to patient care in the clinical setting.

Application of a Bioactive/Bioresorbable Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/Poly-D/L-lactide Composite with Human Mesenchymal Stem Cells for Bone Regeneration in Maxillofacial Surgery: A Pilot Animal Study.

A novel three-dimensional (3D) porous uncalcined and unsintered hydroxyapatite/poly-d/l-lactide (3D-HA/PDLLA) composite demonstrated superior biocompatibility, osteoconductivity, biodegradability, and plasticity, thereby enabling complex maxillofacial defect reconstruction. Mesenchymal stem cells (MSCs)—a type of adult stem cell—have a multipotent ability to differentiate into chondrocytes, adipocytes, and osteocytes. In a previous study, we found that CD90 (Thy-1, cluster of differentiation 90) and CD271 (low-affinity nerve growth factor receptor) double-positive cell populations from human bone marrow had high proliferative ability and differentiation capacity in vitro. In the present study, we investigated the utility of bone regeneration therapy using implantation of 3D-HA/PDLLA loaded with human MSCs (hMSCs) in mandibular critical defect rats. Microcomputed tomography (Micro-CT) indicated that implantation of a 3D-HA/PDLLA-hMSC composite scaffold improved the ability to achieve bone regeneration compared with 3D-HA/PDLLA alone. Compared to the sufficient blood supply in the mandibular defection superior side, a lack of blood supply in the inferior side caused delayed healing. The use of Villanueva Goldner staining (VG staining) revealed the gradual progression of the nucleated cells and new bone from the scaffold border into the central pores, indicating that 3D-HA/PDLLA loaded with hMSCs had good osteoconductivity and an adequate blood supply. These results further demonstrated that the 3D-HA/PDLLA-hMSC composite scaffold was an effective bone regenerative method for maxillofacial boney defect reconstruction.

Osteogenic potential of human dental pulp-derived mesenchymal stem cells in bone regeneration of rabbit

Background/aim Human dental pulp-derived mesenchymal stem cells (hDP-MSCs) offer a promising source of progenitor cells for regenerative medicine and bone tissue engineering. Cranial defects are common complications that can arise secondary to trauma, surgery, or infection. This study aimed to evaluate the osteogenic differentiation potential of hMSCs isolated from dental pulp of third molar teeth in vitro cultures and the bone regenerative capacity of hDP-MSCs transplanted into induced temporomandibular joint (TMJ) defect in rabbits. Patients and methods hDP-MSCs were isolated from third molar teeth and cultured. Alizarin staining was performed to assess the osteogenic differentiation at the 14th and 28th days. The therapeutic potential of hDP-MSCs in craniofacial bone defects was investigated in the left side of the rabbits’ TMJ. The transplanted cells involved three groups: the osteogenic differentiated DP-MSCs (O), undifferentiated MSCs (M), and control group (cell-free matrix) (C). Cells were loaded on gel foam. Eighteen rabbits were used and sacrificed at subsequent three time points, 4, 6, and 9 weeks, after transplantation, with six rabbits/each time point and two rabbits/each cell group. Histopathological studies were applied to evaluate the healing potential of hDP-MSCs in the induced rabbit TMJ defect. Results hDP-MSCs showed a high proliferative potential and osteogenic differentiation in vitro. Histological results demonstrated a timely correlated mandibular defects’ repair in all the experimental groups, including the control group, with more enhanced bone healing effect for the osteogenic differentiated DP-MSCs. Conclusion hDP-MSCs possess high proliferation capacity and osteogenic differentiation potential in vitro. Histological observations revealed the osteogenic differentiated DP-MSCs have higher bone healing potential than the undifferentiated DP-MSCs at 9 weeks after transplantation, and gel foam promotes bone formation in the control group. The bone regenerative potential of osteogenic differentiated DP-MSCs revealed a significant capacity when implanted in rabbit TMJ defect. Hence, hDP-MSCs could be a promising source for craniofacial bone regeneration.

Clinical Use of Mesenchymal Stem Cells in Bone Regeneration

Clinical Use of Mesenchymal Stem Cells in Bone Regeneration

Application of Stem Cells for Bone Regeneration in Critical-Sized Defects

To discuss tissue bioengineering for critical-sized bone defects. To review the current stem cells that are in use and to describe the importance of an animal model for studying critical-sized bone defects. Bone marrow mesenchymal stem cells (MSCs) are well investigated. Recently, other sources of MSCs have been identified and studied in critical-sized bone defects. As for animal models, several have been used to evaluate the use of stem cells in promoting regeneration in critical-sized bone defects. This review specifically focuses on one of the most widely used and accepted models, the rodent calvarium. Stem cell therapy is promising for bone regeneration, especially for critical-sized bone defects. Additional studies are needed to better understand both the properties and mechanisms of the different types of stem cells, and to develop animal models that mimic human biology.

ASSESSMENT OF HUMAN DENTAL PULP STEM CELLS WITH CHITOSAN SCAFFOLD VERSUS XENOGRAFTS IN IMPLANT OSSEOINTEGRATION. AN EXPERIMENTAL STUDY IN A RABBIT MODEL

Background: Human dental pulp stem cells (hDPSCs) considered as a promising source of mesenchymal stem cells for bone regeneration. It can be used to improve osseointegration of dental implant and improve its stability. Objectives: Assessment of bone healing and implant osseointegration by the use of human dental pulp stem cells with chitosan scaffold and compared the result with xenografts in a rabbit model. Materials &Methods: Eighteen adult white rabbits were used in this study. They were distributed equally into three groups, group I, human dental pulp stem cells and chitosan was used before implant insertion in the tibia. Group II, xenografts were used and group III was the control group. After 12 weeks the animals were sacrificed and assessment of bone formation was accomplished by the used of the histological section using H&E, Masson stain as well as scanning electron microscope (SEM). Results: The highest mean area percent was detected in the stem cell group, followed by the xenograft group, while the control group revealed the lowest mean area percent value. Analysis of variance test revealed a highly significant difference between the studied groups (P=0.00). Comparison between the gap distances (µm) in the three groups measured by electron microscope indicated that the lowest mean gap distance was presented in the stem cells group. Conclusion: human dental pulp stem cells coupled with chitosan is a promising method for bone formation and maturation around dental implant and help in osseointegration.

Multimodal Nanoprobe Based on Upconversion Nanoparticles for Monitoring Implanted Stem Cells in Bone Defect of Big Animal.

Monitoring implanted stem cells in bone regeneration and other cell therapies is of great importance to reveal the mechanism of tissue repair and to optimize clinical treatments. However, big challenge still remained in lacking an imaging nanoprobe. Herein, we designed surface modified upconversion nanoparticles (UCNs) with multimodal imaging capabilities of fluorescence, magnetic resonance imaging (MRI) and dual-energy computed tomography (CT). It was found that the UCNs can label stem cells in an efficient (over 200 pg/cell) and long-term (at least 14 days) manner, with almost no influence on the viability, cell cycle, apoptosis, and multilineage differentiation. Thus, clinical dual-energy CT and MRI were successfully applied to observe the migration of labeled cells on a bone-defect model of rabbit for at least 14 days. The results visualized the gathering of stem cells at the defect site of cortical bone, and the in vivo images were well-correlated with the in vitro fluorescence observation without extra staining. Therefore, a potentially translatable nanoprobe was developed for noninvasive and real-time tracking of cells, which may be meaningful for understanding the bone regeneration in clinic and shed light on the visualization of cells in other cell therapies.

Chitosan composite scaffold combined with bone marrow-derived mesenchymal stem cells for bone regeneration: in vitro and in vivo evaluation.

The study aimed to develop a chitosan (CS)-based scaffold for repairing calvarial bone defects. We fabricated composite scaffolds made of CS and bovine-derived xenograft (BDX), characterized their physicochemical properties including pore size and porosity, absorption, degradation, and compressive strength, compared their efficacy to support in vitro proliferation and differentiation of human jaw bone marrow-derived mesenchymal stem cells (hJBMMSCs), and evaluated their bone regeneration capacity in critical-size rat calvarial defects. The CS/BDX (mass ratio of 40:60) composite scaffold with porosity of 46.23% and pore size of 98.23 μm exhibited significantly enhanced compressive strength than the CS scaffold (59.33 ± 4.29 vs. 18.82 ± 2.49 Kpa). The CS/BDX (40:60) scaffold induced better cell attachment and promoted more osteogenic differentiation of hJBMMSCs than the CS scaffold. The CS/BDX (40:60) scaffold seeded with hJBMMSCs was the most effective in supporting new bone formation, as evidenced by better histomorphometry results, larger new bone area, and more obvious mature lamellar bone formation compared to other groups in rat calvarial defects 8 weeks after implantation. These results suggest that CS/BDX composite scaffold combining with hJBMMSCs has the potential for bone defect regeneration.

Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration.

A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapatite (g-HA)/ poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were observed by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HA/PLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HA/PLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HA/PLGA at 2-8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HA/PLGA, while only fibrous tissues formed in PLGA. The incorporation of g-HA mainly improved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone formation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.