Long-term parenteral administration of 2-hydroxypropyl-β-cyclodextrin causes bone loss

Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SHAM) or ovariectomized (OVX) adult rats were subcutaneously injected with physiological saline, 50, or 200 mg/kg HP-β-CD daily. After 4 months, body weight in OVX rats and uterine weight in SHAM rats were significantly lower after administration of 200 mg/kg HP-β-CD, relative to vehicle controls. At 200 mg/kg, HP-β-CD was hepatotoxic as measured by increased serum transaminases, and reduced serum albumin. Moreover, 200 mg/kg HP-β-CD led to decreased vertebral and tibial bone mineral density (BMD), and to cortical thinning at the tibial shaft. Bone loss in HP-β-CD-treated rats was associated with increased bone resorption as measured by increased renal deoxypyridinoline excretion. Although 50 mg/kg HP-β-CD was devoid of overt signs of organ toxicity and did not impair BMD, bone resorption was already increased. In summary, subcutaneous long-term administration of HP-β-CD at a daily dose of 200 mg/kg led to increased bone resorption and subsequent bone loss. Minor alterations in bone metabolism were also seen at 50 mg/kg.     

Endochondral bone growth,bone calcium accretion,and bone mineral density: how are they related?

Endochondral bone growth in young growing mammals or adult mammals with persistent growth plates progresses from proliferation, maturation and hypertrophy of growth plate chondrocytes to mineralization of cartilaginous matrix to form an osseous tissue. This complex process is tightly regulated by a number of factors with different impacts, such as genetics, endocrine/paracrine factors [e.g., PTHrP, 1,25(OH)₂D₃, IGF-1, FGFs, and prolactin], and nutritional status (e.g., dietary calcium and vitamin D). Despite a strong link between growth plate function and elongation of the long bone, little is known whether endochondral bone growth indeed determines bone calcium accretion, bone mineral density (BMD), and/or peak bone mass. Since the process ends with cartilaginous matrix calcification, an increase in endochondral bone growth typically leads to more calcium accretion in the primary spongiosa and thus higher BMD. However, in lactating rats with enhanced trabecular bone resorption, bone elongation is inversely correlated with BMD. Although BMD can be increased by factors that enhance endochondral bone growth, the endochondral bone growth itself is unlikely to be an important determinant of peak bone mass since it is strongly determined by genetics. Therefore, endochondral bone growth and bone elongation are associated with calcium accretion only in a particular subregion of the long bone, but do not necessarily predict BMD and peak bone mass.     

Combination of BMP-2-releasing gelatin/β-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects

The objective of this study is to evaluate the feasibility of gelatin sponges incorporating β-tricalcium phosphate (β-TCP) granules (gelatin/β-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/β-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/β-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation.     

Constructing nanosized cell-type tissue-engineered bone for repair of mandibular bone defects北大核心

BACKGROUND: Nanosized cell-type tissue-engineered bone is a good scaffold material possessing the merits of stem cells and nanomaterials to fabricate bone and soft tissue formation. OBJECTIVE:To explore the method of constructing nano-sized cell-type tissue-engineered bone and to explore its application in the repair of mandibular bone defects. METHODS: One New Zealand white rabbit was taken to isolate bone marrow stromal stem cells by centrifugation. Then, the cells were induced to differentiate into osteoblasts. Osteoblasts (3x108/L, 10 µL) were inoculated into the prepared nano-phase hydroxyapatite/collagen composite to produce the nano-sized cell-type tissue-engineered bone. Another 20 New Zealand white rabbits were taken to make a unilateral puncture-type bone defect model of 15 mmx8 mm. These model rabbits were thereafter randomized into control and artificial bone groups (n=10 per group), followed by no intervention and implantation of nano-sized cell-type tissue-engineered bone, respectively. Repair effects were compared between the two groups. RESULTS AND CONCLUSION: (1) Under the inverted microscope, osteoblasts grew along the material in each group, and the number of cells increased with the prolongation of the culture time. (2) Under the scanning electron microscope, a large number of spindle- or polygon-shaped adherent cells grew well on the surface of the tissue-engineered bone. (3) The defect in the artificial bone group was lessened at 4 weeks after implantation and disappeared at 8 weeks after implantation, and there was no clear boundary with the surrounding tissue. In the control group, the defect size changed little at 4 weeks and reduced at 8 weeks after implantation, and a clear boundary with the surrounding tissue was observed. (4) Bone density, trabecular thickness and trabecular number were significantly higher in the artificial bone group than the control group at 4 and 8 weeks after implantation (P < 0.05). (5) At 4 weeks after implantation, many new bones at the defect site were detected in the artificial bone group, and a large number of mature bone cells were visible at 8 weeks. In the control group, a few osteoblasts were found at the defect site with low bone maturation at 4 and 8 weeks after implantation. These findings suggest that the implantation of nanosized cell-type tissue-engineered bone into the defect site can considerably promote defect healing and achieve ideal repair effects. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Repair of rabbit radial bone defects using bone morphogenetic protein-2 combined with 3D porous silk fibroin/β-tricalcium phosphate hybrid scaffolds

Our study aimed to investigate the effect of bone morphogenetic protein-2 (BMP-2) bound to silk fibroin and β-tricalcium phosphate (SF/β-TCP) hybrid on the healing of critical-size radial defects in rabbits. A 15-mm critical-size defect was induced at mid-diaphysis in the left radius of 20 New Zealand white rabbits (average age, 3.5 months; weight, 2.5–3.0 kg). The animals were randomized into Group 1 (SF/β-TCP combined with BMP-2), Group 2 (SF/β-TCP alone), and Group 3 (nothing implanted). Radiographs were obtained every 2 weeks and euthanasia was performed after 8 weeks for visual, radiological, micro-computed tomography (micro-CT), and histological studies. Eight weeks after implantation (SF/β-TCP combined with BMP-2), radiographs showed that new bone formed on the surface of the implant and had bridged the defect in Group 1. Micro-CT imaging also confirmed the formation of new bone around the implant, and the newly formed bone was quantified. Histological examination revealed newly formed bone in the implanted area. Meanwhile, there was no formation of new bone in Group 3. Among the groups, most active formation of new bones was found in Group 1, while there was no difference between Group 2 and Group 3. Based on these results, we concluded that BMP-2-SF/β-TCP showed significant improvement in healing of critical-size defects. Therefore, the combination of BMP-2 and SF/β-TCP would be useful in the field of bone tissue engineering.     

Does bone perfusion/reperfusion initiate bone remodeling and the stress fracture syndrome?

Stress fractures have been proposed to arise from repetitive activity of training inducing an accumulation of microfractures in locations of peak strain. However, stress fractures most often occur long before accumulation of material damage could occur; they occur in cortical locations of low, not high, strain; and intracortical osteopenia precedes any evidence of micro-cracks. We propose that this lesion arises from a focal remodeling response to site-specific changes in bone perfusion during redundant axial loading of appendicular bones. Intramedullary pressures significantly exceeding peak arterial pressure are generated by strenuous exercise and, if the exercise is maintained, the bone tissue can suffer from ischemia caused by reduced blood flow into the medullary canal and hence to the inner two-thirds of the cortex. Site specificity is caused by the lack, in certain regions of the cortex, of compensating matrix-consolidation-driven fluid flow which brings nutrients from the periosteal surface to portions of the cortex. Upon cessation of the exercise, re-flow of fresh blood into the vasculature leads to reperfusion injury, causing an extended no-flow or reduced flow to that portion of the bone most strongly denied perfusion during the exercise. This leads to a cell-stress-initiated remodeling which ultimately weakens the bone, predisposing it to fracture.     

3D-printed prostheses for large bone defect reconstruction following bone tumor surgery北大核心

BACKGROUND: Tumor segment resection is one of the standard methods for the treatment of bone tumors. However, the reconstruction of bone defects atumor resection faces many challenges. A growing number of researchers are focusing on 3D-printed prostheses for bone defect repair and reconstruction following bone tumor surgery. OBJECTIVE: To explore the feasibility of 3D-printed prostheses in the reconstruction of large bone defect following bone tumor surgery and to evaluate the postoperative outcomes. METHODS: Retrospective analysis of clinical data of 24 patients [19 males and 5 females, age 23.8 (6-61) years] who underwent bone tumor resection and 3D-printed prosthesis implantation in the Department of Bone Oncology, the First Affiliated Hospital of Xinjiang Medical University from December 2020 to September 2021 was conducted. There were 7 cases with distal femur tumor, 5 with pelvis tumor, 4 with proximal tibia tumor, 3 with middle femur tumor, 1 with distal tibia tumor, 1 with proximal humerus tumor, 1 with middle humerus tumor, 1 with scapula tumor, 1 with ulna tumor, and 22 cases with primary tumors (13 osteosarcoma, 4 Ewing sarcoma, 2 giant cell tumor of bone, 1 chondroblastoma, 1 chondrosarcoma, and 1 osteoblastoma), 2 metastatic carcinoma. Preoperative and postoperative imaging data were recorded and neoadjuvant chemotherapy was administered in 17 cases before surgery. The Musculoskeletal Tumour Society score was used to assess limb function before surgery and 6 months after surgery, and pain was assessed by the Visual Analog Scale, as well as the complications were recorded. RESULTS AND CONCLUSION: (1) All patients undergoing resection of the tumor segment and 3D-printed prosthesis implantation for the reconstruction of the bone defect were followed for 6-49 months, and the results showed that the length of osteotomy was (18.2 ± 7.3) cm and an average intraoperative bleeding volume was 740 (100-3 000) mL. (2) Two patients died of systemic metastasis, the remaining 22 had no pulmonary metastasis or recurrence during the follow-up period, and 1 patient developed aseptic loosening of the prosthesis at 25 months postoperatively. (3) The Musculoskeletal Tumour Society scores were significantly increased, while Visual Analog Scale scores were significantly decreased (P < 0.05) at 6 months postoperatively. (4) The Musculoskeletal Tumor Society score was rated excellent in all 22 patients at the final follow-up. (5) These results suggest that 3D-printed prosthesis is suitable for the reconstruction of large bone defects caused by bone tumor resection. Patients have good postoperative function and few complications. However, further investigations are needed to explore long-term follow-up results. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

CT assisted biomimetic artificial bone des

In the recentyears,bioceramic materials have been widely used in the clinics.They are mainly fabricated as the substitution of human hard tissue,such asartificial bone and false tooth. As a medical implant,those that have similarstructure to human bone have betterbiocompatibility and osteoinductional property.So itis necessary to design bone model close to human bone.　　 A new method,CT(Computed Tomography) assisted design,for designingbiomimetic artificial bone is put forward in this paper…     

Do autologous mesenchymal stem cells augment bone growth and contact to massive bone tumor implants?

This study investigated the hypothesis that spraying autologous mesenchymal stem cells (MSCs) onto grooved hydroxyapatite (HA) coated collars of segmental bone tumor implants would increase bone growth and contact to the implant surface in an ovine model. Autologous MSCs were isolated from bone marrow, grown in culture and during surgery implants in group 1 were sprayed with MSCs, suspended within fibrin glue. Implants in group 2 received no MSC therapy and acted as control. Implants remained in vivo for 6 months. New bone area and contact to the implant was quantified on radiographs and histologically. Radiographic analysis demonstrated greater total bone area in the MSC treated group in both ML (MSC = 79.738 mm2 +/- 22.964; control = 30.135 mm2 +/- 6.717) (p = 0.018) and AP (MSC = 90.338 +/- 19.361 mm2; control = 57.384 +/- 9.035 mm2 (p = 0.074) radiographs at 6 months. Results demonstrated significantly increased bone growth in the MSC group at 2 (p = 0.03) and 3 months (p < 0.05). Histological analysis demonstrated significantly greater bone area adjacent to the collars in the treated group (53.994 +/- 10.641 mm2) when compared with the control group 21.069 +/- 7.339 mm2 (p = 0.020). Increased bone contact in the MSC group (19.833 +/- 8.729 %) was observed when compared with controls (8.667 +/- 8.667%). This novel application of spraying MSCs onto the implant surface has significant implications for the future of successful implant fixation.     

Is hydroxyapatite cement an alternative for allograft bone chips in bone grafting procedures? A mechanical and histological study in a rabbit cancellous bone defect model

To evaluate in vivo performance of hydroxyapatite cement (HAC) as a porous bone graft substitute, HAC was mixed (1:1 ratio) with either porous calcium-phosphate granules (80% tricalcium phosphate, 20% hydroxyapatite) or defatted morsellized cancellous bone (MCB) allograft and implanted bilaterally in cylindrical drill holes in distal femurs of rabbits. Groups with empty defects and impacted MCB were used for reference. After 8 weeks, one femur from each pair was examined histologically. All contralateral specimens and Time-0 specimens were used for mechanical indentation tests. Histology showed that some empty defects were filled with newly formed osteopenic bone after 8 weeks. The impacted MCB showed remodeling into new vital bone. Incorporation of the HAC/MCB composite was incomplete, whereas minimal new bone ingrowth was found in the HAC/granule composites. Though not different from each other, both composites were significantly stronger than empty defects, incorporated impacted MCB, and intact cancellous bone. At Time 0, the mechanical behavior of impacted MCB was similar to both HAC composites. In conclusion, composites of HAC and porous biomaterials can maintain relatively high strength over 8 weeks in vivo, but their incorporation into a new bony structure is slower than impacted MCB. The HAC/MCB composite showed favorable incorporation behavior.     

The effects of a novel-reinforced bone substitute and Colloss®E on bone defect healing in sheep

Hydroxyappatite-β-tricalciumphosphate (HA/β-TCP) was reinforced with poly(D,L)-lactic acid (PDLLA) to overcome its weak mechanical properties. Two substitutes with porosities of 77% and 81% HA/β-TCP reinforced with 12 wt % PDLLA were tested in compression. The effects of allograft, substitute (HA/β-TCP-PDLLA), Colloss?E, and combination of substitute with Colloss?E on bone formation in vivo were evaluated. Cylindrical critical size defects were created at distal femoral condyles bilaterally in sheep. Titanium implant with concentric gap filling with one of the four materials was inserted. After 9 weeks, the sheep were sacrificed. Implants with surrounding bone were harvested and sectioned into two parts: one for microcomputed tomography scanning and push-out test, and one for histomorphometry. The 77% HA/β-TCP reinforced with PDLLA had similar mechanical properties to human cancellous bone and was significantly stronger than the HA/β-TCP without PDLLA. Microarchitecture of gap mass was significantly changed after implantation for all groups. Allograft had stronger shear mechanical properties than the other three groups, whereas there were no significant differences between the other three groups. Significant new bone formation could be seen in vivo in all four groups and there were no significant differences between them. The PDLLA-reinforced substitute seems to be good alternative substitute material for bone healing in sheep. Further investigations should be performed to validate this novel substitute material. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.     

Fresh frozen bone in femoral impaction grafting: can developments in bone regeneration improve on this?

Major advances in the understanding of bone regeneration have led to revolutionary applications of bone conduction and induction. Revision hip surgery is on the increase with an active, ageing population demanding increased quality of life. The technically demanding instrumentation and materials necessary for revision prosthetic hip replacements have been rapidly incorporated into clinical practice. Unfortunately, advantage has not been taken of the basic and fundamental principles of bone induction and regeneration, available for many years now. In impaction grafting for revision hip replacements where fresh frozen bone is currently used as a standard, we argue and demonstrate from the literature why this technique is biologically inferior to the results which potentially can be gained by exploiting osteoinductive grafts such as demineralised bone matrix, hydroxyapetite, and inductive factors such as bone morphogenetic proteins.     

Newly developed Sr-substituted α-TCP bone cements

New bone cements made of Sr-substituted brushite-forming α-tricalcium phosphate (α-TCP) were prepared and characterized in the present work. The quantitative phase analysis and structural refinement of the starting powders and of hardened cements were performed by X-ray powder diffraction and the Rietveld refinement technique. Isothermal calorimetry along with setting time analysis allowed a precise tracing of the setting process of the pastes. The pastes showed exothermic reactions within the first 10–15 min after mixing and further release of heat after about 1 h. An apatitic phase formed upon immersion of the hardened cements in simulated body fluid for 15 and 30 days due to the conversion of brushite into apatite confirming their in vitro mineralization capability. The compressive strength of the wet cement specimens decreased with increasing curing time, being higher in the case of Sr-substituted CPC.The results suggest that the newly developed Sr-substituted brushite-forming α-TCP cements show promise for uses in orthopaedic and trauma surgery such as in filling bone defects.     

Biodentine enhances the proliferation and differentiation of osteoblasts through upregulating bone morphogenetic protein-2北大核心

BACKGROUND: Biodentine is a new kind of biocompatible calcium silicate dental restoration material. It can not only increase the secretion of growth factors in dental pulp cells, but also induce the mineralization of dentin. However, the research of Biodentine in bone repair is few. OBJECTIVE: To investigate the effects of Biodentine on the proliferation and differentiation of bone morphogenetic protein-2 interfered mouse osteoblast precursor cell lines by constructing mouse osteoblast precursor cell lines in which bone morphogenetic protein-2 was interfered. METHODS: The 0.1, 1, 10, and 100 g/L Biodentine extract was applied to mouse osteoblast precursor cells for 24 hours. The optimal concentration of 10 g/L was selected by CCK-8 and alkaline phosphatase for the following experiments. Biodentine extract was used to treat mouse osteoblast precursor cells for 1, 3, 5 and 7 days, and the non-intervention group was used as the control group. The cell proliferation and osteogenic differentiation were observed by CCK-8 assay and alkaline phosphatase activity test. Mouse osteoblast precursor cell lines were constructed by interfering with bone morphogenetic protein-2. The proliferation and osteogenic differentiation of cells were observed by CCK-8 assay and alkaline phosphatase activity test. The mouse osteoblast precursor cell lines interfering with bone morphogenetic protein-2 were constructed. The Biodentine group was added with 10 g/L Biodentine extract, and the non-intervention group was set as the control. After 24 and 48 hours of treatment, the proliferation and osteogenic differentiation of the cells were observed by CCK-8 assay and alkaline phosphatase activity test. After 24 hours of treatment, the expression levels of alkaline phosphatase mRNA and protein were detected by real-time PCR and western blot assay. RESULTS AND CONCLUSION: (1) 10 g/L Biodentine extract could promote the proliferation and osteogenic differentiation of mouse osteoblast progenitor cells at 1, 3, 5 and 7 days. (2) Interfering with bone morphogenetic protein-2 could inhibit the proliferation and osteogenic differentiation of mouse osteoblast progenitor cells. (3) The cell proliferation and osteogenic differentiation abilities of Biodentine group were higher than those of control group at 24 and 48 hours (P < 0.05), and the expression levels of alkaline phosphatase mRNA and protein of Biodentine group were higher than those of the control group (P<0.05). (4) The results showed that 10 g/L Biodentine could enhance the proliferation and osteogenic differentiation of osteoblasts through bone morphogenetic protein-2. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Are menopausal symptoms associated with bone mineral density and changes in bone mineral density in premenopausal women?

Background: The relationship between menopausal symptoms and bone mineral density (BMD) was examined in 290 premenopausal women, ages 44–50 years, participating in a randomized clinical trial of a dietary and exercise intervention: The Women's Healthy Lifestyle Project. Methods: Information on hot flashes (presence, absence), menstrual cycles (irregular, regular) and menstrual flow per period (variable, same) over the past 6 months was collected at entry. Participants reporting at least one menopausal symptom were classified as symptomatic and compared to those having no symptoms. Bone mineral density (BMD) at the lumbar spine (L1–L4), total hip and whole-body were made at baseline and at 30 months using a dual-energy X-ray absorptiometer (Hologic QDR 2000 densitometer). Results: Baseline BMD at the spine, hip and whole-body were significantly reduced in women reporting menopausal symptoms compared to asymptomatic women, after adjustment for age, weight and intervention status (all p<0.05). Women with irregular menstrual cycles had greater annualized rates of bone loss at the spine and hip than asymptomatic women (spine, −0.77 (1.6)% per year vs. −0.19 (1.0)% per year, p=0.0043; hip, −0.37 (1.1)% per year vs. −0.04 (1.0)% per year, p=0.061), after adjustments for age, percent change in weight, intervention status, and baseline BMD. Similar findings were not found for whole-body BMD. Conclusions: These results suggest that menopausal symptoms are useful for the effective identification of premenopausal women at higher risk of low BMD and perhaps, of osteoporosis.     

Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway

Immune reactions play important roles in determining the in vivo fate of bone substitute materials, either in new bone formation or inflammatory fibrous tissue encapsulation. The paradigm for the development of bone substitute materials has been shifted from inert to immunomodulatory materials, emphasizing the importance of immune cells in the material evaluation. Macrophages, the major effector cells in the immune reaction to implants, are indispensable for osteogenesis and their heterogeneity and plasticity render macrophages a primer target for immune system modulation. However, there are very few reports about the effects of macrophages on biomaterial-regulated osteogenesis. In this study, we used β-tricalcium phosphate (β-TCP) as a model biomaterial to investigate the role of macrophages on the material stimulated osteogenesis. The macrophage phenotype switched to M2 extreme in response to β-TCP extracts, which was related to the activation of calcium-sensing receptor (CaSR) pathway. Bone morphogenetic protein 2 (BMP2) was also significantly upregulated by the β-TCP stimulation, indicating that macrophage may participate in the β-TCP stimulated osteogenesis. Interestingly, when macrophage-conditioned β-TCP extracts were applied to bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of BMSCs was significantly enhanced, indicating the important role of macrophages in biomaterial-induced osteogenesis. These findings provided valuable insights into the mechanism of material-stimulated osteogenesis, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute materials.     

Chondrogenic pre-induction of human mesenchymal stem cells on β-TCP: Enhanced bone quality by endochondral heterotopic bone formation

New techniques to heal bone defects include the combination of bone substitute materials with mesenchymal stem cells (MSC). To find solutions not hampered by low material resorbability or high donor variability of human MSC, the potency of such composites is usually evaluated by heterotopic bone formation assays in immunocompromised animals. The aim of this study was to investigate whether resorbable phase-pure β-tricalcium-phosphate (β-TCP) could support heterotopic bone formation by MSC comparable to partially resorbable hydroxyapatite/tricalcium-phosphate (HA/TCP). Furthermore, in light of disappointing results with osteogenic in vitro priming of MSC, we tested whether chondrogenic pre-induction of constructs may allow for enhanced bone formation by triggering the endochondral pathway. β-TCP granules of three different sizes and HA/TCP were seeded with MSC and transplanted subcutaneously into immunocompromised mice either immediately or after a chondrogenic pre-induction for 6 weeks. After 8 weeks, explants were analysed by histology. β-TCP seeded with unprimed MSC revealed intramembranous bone formation without haematopoietic marrow with 3.8-fold more bone formed with granules smaller than 0.7 mm than with 0.7–1.4 mm particles (p ? 0.018). Chondrogenic pre-induction of β-TCP/MSC composites resulted in collagen type II and proteoglycan-rich cartilage-like tissue which, after transplantation, underwent endochondral ossification, yielding ectopic bone produced by human cells while haematopoietic marrow was derived from the mouse. Transdifferentiation of MSC-derived chondrocytes to osteoblasts or direct osteogenesis of cartilage-resident MSC is postulated to explain the human origin of new bone. In conclusion, β-TCP was significantly more osteo-permissive (p = 0.004) than HA/TCP for human MSC, and chondrogenic priming of β-TCP/MSC represented a superior approach capable of supporting full bone formation, including marrow organization.     

Solid freeform fabrication of bone tissue engineering scaffolds

INTRODUCTION　　 Tissue engineering is a promising approach to large segmental bone repair fortrauma,replacement surgery,skeletal deficiency or abnormal development. Thefabrication of boneregeneration scaffoldswith appropriate bone conductive property,bone inductive property,biodegradation property and mechanical properties is thecrux of this approach. Traditional scaffold fabrication technologies include phaseseparation technology,salt-leaching technology and gas-induced foaming technolo-…