Macroporous Biphasic Calcium Phosphate Research Articles

Effect of Citric Acid as a Porogenic Agent for Fabrication of Macroporous Biphasic Calcium Phosphate Scaffolds

Effect of Citric Acid as a Porogenic Agent for Fabrication of Macroporous Biphasic Calcium Phosphate Scaffolds

Effect Investigation of Ammonium Bicarbonate and Polyethylene Wax as Pore-Forming Agents on the Physicochemical Properties of Macroporous Biphasic Calcium Phosphate Bioceramics Processed by Space-Holder Technique

Effect Investigation of Ammonium Bicarbonate and Polyethylene Wax as Pore-Forming Agents on the Physicochemical Properties of Macroporous Biphasic Calcium Phosphate Bioceramics Processed by Space-Holder Technique

Improved bone regeneration using collagen-coated biphasic calcium phosphate with high porosity in a rabbit calvarial model

Many growth factors have been paired with synthetic bone grafts to accelerate the healing process in vivo. Collagen has been particularly examined as a mediator of the enhancement of bone regeneration. This study investigated the new bone formation potential of micro–macroporous biphasic calcium phosphate (m-BCP), high porosity biphasic calcium phosphate (p-BCP), and collagen-coated p-BCP (cp-BCP) using a rabbit calvarial defect model. At 2 or 8 weeks after surgery, bone tissue was collected. The three-dimensional analysis of new bone formation using synchrotron radiation micro-computed tomography and histological study were conducted. The new bone formation values observed at 2 and 8 weeks in the negative control, m-BCP, p-BCP, and cp-BCP groups were 11.21 ± 1.36 mm3, 21.75 ± 1.18 mm3, 24.59 ± 1.26 mm3, and 29.54 ± 2.72 mm3, respectively, and 18.34 ± 3.99 mm3, 32.27 ± 3.78 mm3, 43.12 ± 1.61 mm3, and 58.20 ± 3.84 mm3, respectively. New bone formation was greatest in the cp-BCP group, while the amount of new bone at 8 weeks was higher than at 2 weeks in each group. The use of cp-BCP to enhance new bone formation during the healing period could improve bone regeneration.

Evaluation of the Apical Complex and the Coronal Pulp as a Stem Cell Source for Dentin-pulp Regeneration

IntroductionThis study compared the stemness and differentiation potential of stem cells derived from the apical complex (apical complex cells [ACCs]) and coronal pulp (dental pulp stem cells [DPSCs]) of human immature permanent teeth with the aim of determining a more suitable source of stem cells for regeneration of the dentin-pulp complex. MethodsACC and DPSC cultures were established from 13 human immature permanent teeth using the outgrowth method. The proliferation capacity and colony-forming ability of ACCs and DPSCs were evaluated. ACCs and DPSCs were analyzed for mesenchymal stem cell markers using flow cytometry. The adipogenic and osteogenic differentiation potential of ACCs and DPSCs were evaluated using the quantitative real-time polymerase chain reaction and histochemical staining. ACCs and DPSCs were transplanted subcutaneously in immunocompromised mice using macroporous biphasic calcium phosphate as a carrier. The histomorphologic characteristics of the newly formed tissues were verified using hematoxylin-eosin staining and immunohistochemical staining. Quantitative alkaline phosphatase analysis and quantitative real-time polymerase chain reaction using BSP, DSPP, POSTN, and ColXII were performed. ResultsACCs and DPSCs showed similar cell proliferation potential and colony-forming ability. The percentage of mesenchymal stem cell markers was similar between ACCs and DPSCs. In the in vitro study, ACCs and DPSCs showed adipogenic and osteogenic differentiation potential. In the in vivo study, ACCs and DPSCs formed amorphous hard tissue using macroporous biphasic calcium phosphate particles. The quantity and histomorphologic characteristics of the amorphous hard tissue were similar in the ACC and DPSC groups. Formation of periodontal ligament–like tissue, positive to Col XII, was observed in ACC transplants, which was absent in DPSC transplants. ConclusionsACCs and DPSCs showed similar stemness, proliferation rate, and hard tissue–forming capacity. The notable difference was the periodontal ligament–like fiber-forming capacity of ACCs, which indicates the presence of various lineages of stem cells in the apical complex compared with the coronal pulp. Regarding regeneration of the dentin-pulp complex, the coronal pulp can be a suitable source of stem cells considering its homogenous lineages of cells and favorable osteo/odontogenic differentiation potential.

Effect of metformin on dental pulp stem cells attachment, proliferation and differentiation cultured on biphasic bone substitutes

ObjectiveTo evaluate to the effect of metformin on attachment of human dental pulp stem cells (hDPSCs) and their proliferation and osteogenic differentiation on biphasic hydroxyapatite/beta-tricalcium phosphate granules of macro-porous biphasic calcium phosphate (MBCP). Materials and methodsThis in vitro study included four groups: A:hDPSCs + MBCP + Metfromin, B:hDPSCs + MBCP, C:hDPSCs + Metformin and D:hDPSCs (control). Attachment of hDPSCs to bone granules in groups A and B was observed by scanning electron microscopy on days 1 and 7 of cultivation. Cell viability was assessed by MTT assay on days 1, 3, and 7 after cell seeding. Differentiation of the hDPSCs was assessed by measurement of alkaline phosphatase activity on days 3, 7, 14 and 21 after cell culturing in standard and osteogenic media. The data was analyzed by two-way ANOVA at a significance level of p = 0.05. ResultsThe hDPSCs had firmly attached to the surface of MBCP granules, especially in group A. The MTT values increased in all groups from day 1 to day 7 (p < 0.001). The highest MTT values were observed in group C followed by the control group and groups A and B (p < 0.001). Alkaline phosphatase activity also increased in all groups between days 3 to 21 (p < 0.001) except between days 7 and 14 in standard media (p = 0.094). In standard media, groups with MBCP granules (A and B) showed higher activity (p < 0.05). In osteogenic media, the groups with metformin (A and C) showed higher alkaline phosphatase activity (p < 0.05). ConclusionThis in vitro study showed that 100 Mol/L metformin increased attachment and proliferation of hDPSCs on biphasic granules. Osteogenic differentiation of hDPSCs also increased in the presence of metformin.

Synthesis, chemical and microstructural characterization of micro macroporous biphasic calcium phosphate granules

A route based on calcium phosphate emulsions with addition of glycolic acid as pore former was developed for synthesizing porous nanocrystalline biphasic calcium phosphate ceramics. The method is low cost and gives a biphasic calcium phosphate composed of 88% β-tricalcium phosphate and 12% hydroxyapatite. The material obtained is characterized by scanning electron microscopy, X-ray diffraction and X-ray fluorescence techniques, and the specific surface area is determined by the Brunauer, Emmett and Teller method. The small crystalline domain sizes obtained (68 and 87 nm for β-tricalcium phosphate and hydroxyapatite phases, respectively) allow a major contact reaction and stability in the interphase between the implanted material and natural bone, as well as a better promotion effect on the early bone in-growth. The improvement of the physical, chemical and structural properties by the balanced combination of the ceramic phases, the small crystallite size, the high porosity and high specific surface area obtained is a desirable characteristic in bone tissue engineering and encourages the performance of animal studies in vivo to evaluate their use for applications such as bone replacement in humans. Copyright © 2017 John Wiley & Sons, Ltd.

Calcium-phosphate ceramics and polysaccharide-based hydrogel scaffolds combined with mesenchymal stem cell differently support bone repair in rats

Research in bone tissue engineering is focused on the development of alternatives to autologous bone grafts for bone reconstruction. Although multiple stem cell-based products and biomaterials are currently being investigated, comparative studies are rarely achieved to evaluate the most appropriate approach in this context. Here, we aimed to compare different clinically relevant bone tissue engineering methods and evaluated the kinetic repair and the bone healing efficiency supported by mesenchymal stem cells and two different biomaterials, a new hydrogel scaffold and a commercial hydroxyapatite/tricalcium phosphate ceramic, alone or in combination.Syngeneic mesenchymal stem cells (5 × 105) and macroporous biphasic calcium phosphate ceramic granules (Calciresorb C35®, Ceraver) or porous pullulan/dextran-based hydrogel scaffold were implanted alone or combined in a drilled-hole bone defect in rats. Using quantitative microtomography measurements and qualitative histological examinations, their osteogenic properties were evaluated 7, 30, and 90 days after implantation. Three months after surgery, only minimal repair was evidenced in control rats while newly mineralized bone was massively observed in animals treated with either hydrogels (bone volume/tissue volume = 20%) or ceramics (bone volume/tissue volume = 26%). Repair mechanism and resorption kinetics were strikingly different: rapidly-resorbed hydrogels induced a dense bone mineralization from the edges of the defect while ceramics triggered newly woven bone formation in close contact with the ceramic surface that remained unresorbed. Delivery of mesenchymal stem cells in combination with these biomaterials enhanced both bone healing (>20%) and neovascularization after 1 month, mainly in hydrogel.Osteogenic and angiogenic properties combined with rapid resorption make hydrogels a promising alternative to ceramics for bone repair by cell therapy.

Prospective Study of the Mastoid Plasties Using Resorbable Bioceramic MBCP&lt;sup&gt;®&lt;/sup&gt; in Surgery of Cholesteatoma

Tympanoplasty is the reference for cholesteatoma treatment in ear, nose, and throat (ENT surgery), with the realization of a closing technique, which preserves the external auditory canal. An insufficient pneumatisation is an element favoring the occurrence and recurrence of cholesteatoma. In a prospective clinical pilot study, we have realized the reconstruction of the mastoid cortical bone by a Micro Macroporous Biphasic Calcium Phosphate bioceramics disks (MBCPTM Biomatlante France) using the closed technique, in order to maintain or increase the mastoid pneumatisation. Eleven patients were used for this study, and some of them have a sample collection for histomorphometry and histopathological analysis. Bone regeneration at the expense of the bioceramic was observed. The size and shape of the disk was not preserved due to the large resorption and bone ingrowth at the expense of the implant. However 6 patients presented cholesteatoma recurrence. The MBCPTM disks are able to reconstruct the mastoid cortical and maintain the mastoid pneumatisation contrarily to the technique of filling the mastoid cavity. However, the high rate of cholesteatoma recurrence observed in our study, confirmed the interest to fill mastoid that suppress airspace posterior cavities.

Guided bone regeneration using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-cross-linked type-I collagen membrane with biphasic calcium phosphate at rabbit calvarial defects.

BackgroundIn-vitro and animal studies using EDC cross-linked membranes have shown great resistance to enzymatic digestion as well as low cytotoxicity, and indicated its potential expediency as a barrier membrane for guided bone regeneration (GBR). The purpose of this study was to evaluate the efficacy, biocompatibility and degradation kinetics of a novel 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-cross-linked type I collagen membrane for regeneration of rabbit calvarial defects. EDC cross-linked type I collagen membrane and macroporous biphasic calcium phosphate (MBCP) consisting of 60 % hydroxyapatite and 40 % β-tricalcium phosphate were used in this study. Four circular defects (ø = 8 mm) were created in each calvarium of 12 male white rabbits. The experimental groups randomly allocated to the defects were as follows – (1) sham control, (2) EDC-cross-linked collagen membrane (EDC membrane), (3) bone graft (BG), and (4) bone graft with collagen membrane (B-EDC membrane). Specimens were harvested at 2 weeks (n = 6) and 8 weeks (n = 6) postoperatively for observational histology and histometrical analysis.ResultThe histologic observation showed close adaptation of the EDC membrane to the defect perimeters along with vascularization of the membrane at 2 weeks. Direct apposition of new bone on to the collagen matrix could be observed displaying adequate tissue integration. Collapsing of the central portion of the membrane could be seen in the EDC membrane group, and both BG and B-EDC membrane groups showed greater total augmented area and new bone area than the EDC membrane group. The membrane was largely unresorbed at 2 weeks; and at 8 weeks the overall shape of the membrane was still maintained suggesting sustained barrier function at 8 weeks.ConclusionWithin the limits of this study, it may be concluded that EDC-cross-linked collagen membrane is a safe biomaterial with adequate tissue integration and resorption kinetics to support bone regeneration when used in conjunction with bone filler.

Erratum to: Osteoconduction capacity of human deciduous and permanent teeth ash in a rat calvarial bone defect model

The aim of this study was to confirm the osteoconduction capacities and determine the potential of permanent teeth ash (PTA), and deciduous teeth ash (DTA) as bone substitutes. Rats (n = 71) were divided randomly into four groups: sham, micro macroporous biphasic calcium phosphate (MBCP), PTA, and DTA. A sample of the each group was transplanted into preformed 8-mm calvarial defects (one per rat). The density of new bone was calculated and the crystallinities of the PTA and DTA were analyzed by X-ray diffraction. The degree of new bone formation was high in the MBCP and DTA groups but low in the PTA groups. The DTA was highly crystalline, whereas the PTA was not. The percentages of β-tricalcium phosphate in the DTA and PTA were 10.7 and 3.7 %, respectively. DTA has a high osteoconduction capacity, suggesting that it is a useful bone substitute.

Ectopic Hard Tissue Formation by Odonto/Osteogenically In Vitro Differentiated Human Deciduous Teeth Pulp Stem Cells.

There have been many attempts to use the pulp tissue from human deciduous teeth for dentin or bone regeneration. The objective of this study was to determine the effects of odonto/osteogenic in vitro differentiation of deciduous teeth pulp stem cells (DTSCs) on their in vivo hard tissue-forming potential. DTSCs were isolated from extracted deciduous teeth using the outgrowth method. These cells were exposed to odonto/osteogenic stimuli for 4 and 8 days (Day 4 and Day 8 groups, respectively), while cells in the control group were cultured in normal medium. The in vitro differentiated DTSCs and the control DTSCs were transplanted subcutaneously into immunocompromised mice with macroporous biphasic calcium phosphate and sacrificed at 8 weeks post-implantation. The effect of odonto/osteogenic in vitro differentiation was evaluated using alkaline phosphatase (ALP) staining and quantitative reverse transcription polymerase chain reaction (RT-PCR). The in vivo effect was evaluated by qualitative RT-PCR, assessment of ALP activity, histologic analysis, and immunohistochemical staining. The amount of hard tissue was greater in Day 4 group than Day 8 group (p = 0.014). However, Day 8 group generated lamellar bone-like structure, which was immunonegative to anti-human dentin sialoprotein with significantly low expression level of DSPP compared with the control group (p = 0.008). This study demonstrates that odonto/osteogenic in vitro differentiation of DTSCs enhances the formation of bone-like tissue, instead of dentin-like tissue, when transplanted subcutaneously using MBCP as a carrier. The odonto/osteogenic in vitro differentiation of DTSCs may be an effective modification that enhances in vivo bone formation by DTSCs.

Macroporous biphasic calcium phosphate scaffolds reinforced by poly-L-lactic acid/hydroxyapatite nanocomposite coatings for bone regeneration

Three-dimensional (3D) interconnected porous scaffolds with biomimetic hierarchical architectures and mechanical characteristics are critical for the success of bone regeneration. In this paper, biphasic calcium phosphate (BCP) scaffolds were coated with medical-grade poly-L-lactic acid/hydroxyapatite (mPLLA/HA) nanocomposites to create controlled surface roughness while remaining the interconnected porous structures. Such mPLLA/HA coatings substantially improved the compressive strength of the scaffolds to 3.17–3.95MPa, in contrast to 0.31MPa for the as-prepared bare porous BCP scaffolds. Moreover, these mPLLA/HA-coated porous scaffolds were demonstrated to provide excellent support to the growth and proliferation of human barrow mysenchymal stem cells (hBMSCs). The hBMSCs-seeded mPLLA/HA-coated scaffolds were implanted to large necrotic lesions in the rabbit femoral head. New bone tissues were observed after two months, followed by gradient new bone formation over months according to H&E and Masson staining analysis. These results suggest that the mPLLA/HA-coated BCP scaffolds with improved mechanical strength and osteogenesis may be applied for bone regeneration.

Osteoconduction capacity of human deciduous and permanent teeth ash in a rat calvarial bone defect model.

The aim of this study was to confirm the osteoconduction capacities and determine the potential of permanent teeth ash (PTA), and deciduous teeth ash (DTA) as bone substitutes. Rats (n = 71) were divided randomly into four groups: sham, micro macroporous biphasic calcium phosphate (MBCP), PTA, and DTA. A sample of the each group was transplanted into preformed 8-mm calvarial defects (one per rat). The density of new bone was calculated and the crystallinities of the PTA and DTA were analyzed by X-ray diffraction. The degree of new bone formation was high in the MBCP and DTA groups but low in the PTA groups. The DTA was highly crystalline, whereas the PTA was not. The percentages of β-tricalcium phosphate in the DTA and PTA were 10.7 and 3.7%, respectively. DTA has a high osteoconduction capacity, suggesting that it is a useful bone substitute.

Bioceramic and Fibrin Sealant in High Tibial Valgus Osteotomy: Prospective Clinical Study

The association of Micro Macroporous Biphasic Calcium Phosphate granules and t fibrin sealant has been developed to answer a challenging request of orthopaedic surgeons: a biocompatible, osteogenic, mouldable, and self-hardening bone substitute able to fill bone defects. The aim of this study was the evaluation of the performance and safety of the bioactive composite in regeneration of functional bone. A clinical study design was set up as an exploratory prospective French multicentric phase II study sponsored by INSERM. The application was the HTVO (Tibial Osteotomy of Valgisation) using osteosynthesis and bone substitute (BS) for filling the space created. The follow up was 12 months with safety checks, clinical assessments, high-sensitivity X-ray, and CT-scan imaging. A bone sample was collected from the reconstructed area at 12 months. 13 patients with stage I gonarthrosis have been included in the study. This clinical follow up revealed only one case of correction loss. X-ray and CT-scan imaging indicated a progressive disappearance of the peripheric radioluency and a decrease of the radiopacity of the implanted area due to bioceramic resorption and bone ingrowth at the expense of the implant. Histological analysis revealed BS large resorption and bone ingrowth both into the pores and at the expense of the bioceramic. X-Ray and micro CT scan revealed a well organised and mineralised structure in the newly-formed bone.

Preparation of microporous and macroporous biphasic calcium phosphate scaffolds modified via a biomimetic method for bone tissue engineering applications

Preparation of microporous and macroporous biphasic calcium phosphate scaffolds modified via a biomimetic method for bone tissue engineering applications

Functionalization of scaffolds with chimeric anti-BMP-2 monoclonal antibodies for osseous regeneration

Recent studies have demonstrated the ability of murine anti-BMP-2 monoclonal antibodies (mAb) immobilized on an absorbable collagen sponge (ACS) to mediate de novo bone formation, a process termed antibody-mediated osseous regeneration (AMOR). The objectives of this study were to assess the efficacy of a newly generated chimeric anti-BMP-2 mAb in mediating AMOR, as well as to evaluate the suitability of different biomaterials as scaffolds to participate in AMOR. Chimeric anti-BMP-2 mAb was immobilized on 4 biomaterials, namely, titanium microbeads (Ti), alginate hydrogel, macroporous biphasic calcium phosphate (MBCP) and ACS, followed by surgical implantation into rat critical-size calvarial defects. Animals were sacrificed after 8 weeks and the degree of bone fill was assessed using micro-CT and histomorphometry. Results demonstrated local persistence of chimeric anti-BMP-2 mAb up to 8 weeks, as well as significant de novo bone regeneration in sites implanted with chimeric anti-BMP-2 antibody immobilized on each of the 4 scaffolds. Ti and MBCP showed the highest volume of bone regeneration, presumably due to their resistance to compression. Alginate and ACS also mediated de novo bone formation, though significant volumetric shrinkage was noted. In vitro assays demonstrated cross-reactivity of chimeric anti-BMP-2 mAb with BMP-4 and BMP-7. Immune complex of anti-BMP-2 mAb with BMP-2 induced osteogenic differentiation of C2C12 cells in vitro, involving expression of RUNX2 and phosphorylation of Smad1. The present data demonstrated the ability of chimeric anti-BMP-2 mAb to functionalize different biomaterial with varying characteristics to mediate osteogenesis.

Maxillary Sinus Grafting with Biphasic Calcium Phosphate Ceramics: Clinical and Histologic Evaluation in Man

To evaluate the clinical and histologic aspects of bone formation in maxillary sinus augmentation using macroporous biphasic calcium phosphate (MBCP) comprising hydroxyapatite/tricalcium phosphate (HA/TCP) 60/40 as bone-grafting material. A total of 10 patients and 12 sinuses grafted with MBCP in two-stage sinus augmentation were included in the present study. After a healing period of 6 months, bone core biopsies were harvested during implant insertion and evaluated under light microscopy. The histologic examination showed that the MBCP particles were in close contact with new bone in all biopsies. Histomorphometric evaluation demonstrated that newly formed bone constituted 28.3% ± 2.7%, residual grafted material 27.3% ± 1.2%, and marrow spaces 45.9% ± 1.9%. Histologic investigation showed that the MBCP grafted particles were embedded and integrated in the newly formed bone; this bone was in close and tight contact with the biomaterial particles. Data from the preliminary results demonstrated that MBCP is a biocompatible and osteoconductive material that can be successfully used as a grafting material for sinus floor augmentation.

A Comparison of the Healing Capabilities of Various Grafting Materials in Critical-Size Defects in Guinea Pig Calvaria

To estimate the efficacy of various bone grafting materials in the healing of 8-mm-diameter critical-size defects (CSD) in guinea pig calvaria. In this randomized trial study, critical-size defects were created in the calvaria of 36 guinea pigs 6 months of age. Animals were assigned into three groups and each received one of three experimental protocols. In protocol A, the right-side defect was filled with macroporous biphasic calcium phosphate (MBCP Gel) and the left side was left empty as a control. In protocol B, the right-side defect was filled with demineralized freeze-dried bone allograft (DFDBA) and the left side was filled with Stypro. In protocol C, the right-side defect was filled with Bio-Oss and the left side was filled with autogenous bone. The percentage of new bone formation was evaluated histomorphometrically after 8 weeks. The mean bone formation was 68.19% for autogenous bone, 66.96% for MBCP Gel, 57.28% for Bio-Oss, 50.19% for DFDBA, 18.79% for Stypro, and 10.61% for the empty control. Except for the MBCP Gel and autogenous bone groups (P = .6), the differences between the other groups were statistically significant (P < .05). The results of this study indicated that all the testing materials had different capacities to produce new bone in CSD of guinea pig calvaria. MBCP Gel showed promising results in producing new bone proportionate to the autogenous bone graft group.

Clinical Studies of Anterior Cervical Fusion with PEEK Cages: Comparing Iliac Graft and a Macroporous Biphasic Calcium Phosphate

The objective of the study was to compare clinical efficiency of the fusion after reconstruction with an anatomically shaped PEEK cage associated with a iliac crest autograft or MBCP in the treatment of cervical disc disease in randomized clinical trial. A multicente randomized, comparative and prospective study on 58 patients, with a 12 months follow up are reported. They underwent anterior cervical decompression and fusion being randomized for autologous graft or MBCP. Patients presenting purely degenerative disc disease were implanted with a PEEK cage filled with iliac crest autograft or MBCP. Pain and functionality as well as patients satisfaction were assessed through VAS, Neck Disability Index (NDI) and Patient Satisfaction index were recorded until 24 month follow-up. Radiological evaluation included plain and dynamic short X-rays at each stage of the follow up. The patients satisfaction rates was of 82% in the autograft group versus 96% in the MBCP group. Pain at the donor site was significantly more important in the autograft group at 3 weeks, 3 months and 1 year follow-up. No implant failures were recorded. Previously goat preclinical study was performed. Micro CT, light microscopy and shistomorphometry were related to the high performance of the MBCP insert for filling cage fusion, completing the clinical assessment of our clinical study. The use of MBCP insert is safe and avoids potential graft site morbidity and pain in comparison with an autologous graft procedure.

Gene activated matrices for bone and cartilage regeneration in arthritis

The GAMBA Consortium is developing a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The scientific and technological objectives of this project are complemented with an innovative program of public outreach, actively linking patients and society to the evolvement of this project. The GAMBA platform will implement a concept of spatiotemporal control of regenerative bioactivity on command and demand. A gene activated matrix is a biomaterial with embedded gene vectors that will genetically modify cells embedded in or colonising the matrix. The platform comprises modules that self-adapt to the biological environment and that can be independently addressed with endogenous biological and exogenous physical or pharmacological stimuli, resulting in a temporally and spatially coordinated growth factor gene expression pattern. This reproduces, within the matrix, key elements of natural tissue formation. The modules are a biomimetic hyaluronan gel, a ceramic matrix, growth factor-encoding gene vector nanoparticles, magnetic nanoparticles and mesenchymal stem cells. Anatomical adaptivity is achieved with engineered thermal properties of the polymer matrix, which embeds other modules, selected according to functional requirements. Mechanical support is provided by Micro Macroporous Biphasic Calcium Phosphate (MBCP™), a resorbable material approved for clinical use. Spatiotemporal control of bioactivity and responsiveness to physiological conditions is represented, firstly, in the spatial distribution and release profiles of gene vectors within the composite matrix and, secondly, by letting local and external biological or physical stimuli activate the promoters driving the expression of vector-encoded growth factor transgenes. This concept is implemented by a multidisciplinary team from leading European institutions. Here, we report on the concepts, objectives and some preliminary results of the GAMBA project which is funded in 7th Framework Programme of the European Union THEME [NMP-2009-2.3-1], Biomimetic gels and polymers for tissue repair.