Chitosan: potential use as a bioactive coating for orthopaedic and craniofacial/dental implants

Chitosan is a biopolymer that exhibits osteoconductive, enhanced wound healing and antimicrobial properties which make it attractive for use as a bioactive coating to improve osseointegration of orthopaedic and craniofacial implant devices. Coatings made from 91.2% de-acetylated chitosan were chemically bonded to titanium coupons via silane-glutaraldehyde molecules. The bond strength of the coatings was evaluated in mechanical tensile tests, and their dissolution and cyto-compatibility were evaluated in vitro using cell-culture medium and UMR 106 osteoblastic cells, respectively. The results showed that the chitosan coatings were chemically bonded to the titanium substrate and that the bond strengths (1.5-1.8 MPa) were not affected by gas sterilization. However, the chitosan bond strengths were less than those reported for calcium-phosphate coatings. The gas-sterilized coatings exhibited little dissolution over 8 weeks in cell-culture solution, and the attachment and growth of the UMR 106 osteoblast cells was greater on the chitosan-coated samples than on the uncoated titanium. These results indicated that chitosan has the potential to be used as a biocompatible, bioactive coating for orthopaedic and craniofacial implant devices.     

In vitro assessment of the osteointegrative potential of a novel multiphase anodic spark deposition coating for orthopaedic and dental implants

Hydroxyapatite coatings have been proven to improve the osteointegration of metal implants through a tight binding to the bone mineral phase as well as through favorable osteoblast adhesion and proliferation onto the implant surface. However, hydroxyapatite coatings are not stable and they tend to delaminate from the metal surface when challenged by the mechanical stresses experienced by the implant. Recently, a new multiphase anodic spark deposition (ASD) method has been optimized where the formation of a thick oxide film is followed by the deposition of a calcium phosphate mineral phase and its etching by alkali. The data in this paper demonstrate that this novel type of coating, BioSpark, improves the material osteointegration potential when compared to conventional ASD while offering more mechanical stability. A faster mineralization was obtained by incubation in simulated body fluids and osteoblasts showed better adhesion, proliferation, differentiation, and collagen production. These performances were related to the surface morphology, to the film calcium/phosphate ratio and its surface oxygen content, as well as to a preferential binding of structural proteins such as fibronectin.     

Hydroxyapatite and their use as coatings in dental implants: a review

At present, no standard manufacturing guideline exists for depositing hydroxyapatite (HA) on implant surfaces. Although animal and in vitro studies have reported on the benefits of using HA-coated implants as well as the risks of dissolution, these short-term studies did not demonstrate that the dissolution of the HA coating leads to a loss of implants. In addition, many in vivo and clinical studies did not include the chemical and structural characterization of the coatings, and thus comparisons between studies are difficult. In the clinics, the recommendation is that HA-coated screw implants be used for the anterior maxilla and posterior mandible where the bone depth exceeds 10 mm and when the cortical layer is thinner and spongiosia is less dense. In the posterior maxilla or when the cortical layer is very thin with low density, the use of HA-coated cylindrical implants is recommended. However, there are concerns for using HA-coated implants. The clinician needs to take into consideration the enhanced bacterial susceptibility of HA coatings compared with titanium implants. In addition, the clinician needs to consider the possible failure of HA coatings as a result of coating-substrate interfacial fracture. Finally, besides the surgical skills, it is also important that the clinical investigators be well versed with the materials characterization needed for HA-coated implants, the problems associated with the current HA coatings, and the indications for use. In addition, the correlation between well characterized coatings and their effect on bone formation rate and long-term implant success, coating-implant interfacial strength, and alternative superior coating process need to be investigated further.     

Chitosan: a versatile biopolymer for orthopaedic tissue-engineering

Current tissue engineering strategies are focused on the restoration of pathologically altered tissue architecture by transplantation of cells in combination with supportive scaffolds and biomolecules. In recent years, considerable attention has been given to chitosan (CS)-based materials and their applications in the field of orthopedic tissue engineering. Interesting characteristics that render chitosan suitable for this purpose are a minimal foreign body reaction, an intrinsic antibacterial nature, and the ability to be molded in various geometries and forms such as porous structures, suitable for cell ingrowth and osteoconduction. Due to its favorable gelling properties chitosan can deliver morphogenic factors and pharmaceutical agents in a controlled fashion. Its cationic nature allows it to complex DNA molecules making it an ideal candidate for gene delivery strategies. The ability to manipulate and reconstitute tissue structure and function using this material has tremendous clinical implications and is likely to play a key role in cell and gene therapies in coming years. In this paper we will review the current applications and future directions of CS in articular cartilage, intervertebral disk and bone tissue engineering.     

Cellular compatibility of highly degradable bioactive ceramics for coating of metal implants

Resorbable ceramics can promote the bony integration of implants. Their rate of degradation should ideally be synchronized with bone regeneration. This study examined the effect of rapidly resorbable calcium phosphate ceramics 602020, GB14, 305020 on adherence, proliferation and morphology of human bone-derived cells (HBDC) in comparison to β-TCP. The in vitro cytotoxicity was determined by the microculture tetrazolium (MTT) assay. HBDC were grown on the materials for 3, 7, 11, 15 and 19 days and counted. Cell morphology, cell attachment, cell spreading and the cytoskeletal organization of HBDC cultivated on the substrates were investigated using laser scanning microscopy and environmental scanning electron microscopy. All substrates supported sufficient cellular growth for 19 days and showed no cytotoxicity. On each material an identical cell colonisation of well communicating, polygonal, vital cells with strong focal contacts was verified. HBDC showed numerous well defined stress fibres which give proof of well spread and strongly anchored cells. Porous surfaces encouraged the attachment and spreading of HBDC. Further investigations regarding long term biomaterial/cell interactions in vitro and in vivo are required to confirm the utility of the new biomaterials.     

Laser processing of bioactive tricalcium phosphate coating on titanium for load-bearing implants

Laser-engineered net shaping (LENS), a commercial rapid prototyping (RP) process, was used to coat titanium with tricalcium phosphate (TCP) ceramics to improve bone cell-materials interactions. During LENS coating process, the Nd:YAG laser melts the top surface of Ti substrate in which calcium phosphate powder is fed to create a TCP-Ti composite layer. It was found that an increase in laser power and/or powder feed rate increases the thickness of the coating. However, coating thickness decreased with increasing laser scan speed. TCP coating showed columnar titanium grains at the substrate side of the coating and transitioned to equiaxed titanium grains at the outside. When the scan speed was reduced from 15 to 10mms(-1), coating hardness increased from 882+/-67 to 1049+/-112Hv due to an increase in the volume fraction of TCP in the coating. Coated surfaces showed uniformly distributed TCP particles and X-ray diffraction data confirmed the absence of any undesirable phases, while maintaining a high level of crystallinity. The effect of TCP coating on cell-material interaction was examined by culturing osteoprecursor cells (OPC1) on coated surfaces. The results indicated that TCP coating had good biocompatibility where OPC1 cells attached and proliferated on the coating surface. The coating also initiated cell differentiation, ECM formation and biomineralization.     

Ultrasound: a potential technique to improve osseointegration of dental implants

Dental implants have been widely used in clinic for the restoration of lost teeth in recent decades, but there still remains a great challenge for even a higher success rate and a shorter rehabilitation time. The osseointegration between dental implant and alveolar bone tissue is crucial for a successful implantation. Ultrasound has been proved to be an effective treatment for bone fracture healing. The underlying mechanism of the mechanotransduction pathway involved in cellular responses to ultrasound is still not clear, however, numerous studies have confirmed its ability to enhance osteogenesis and therefore facilitate bone regeneration. In this paper, we hypothesize that this kind of wave might have an ability to strengthen and accelerate osseointegration of dental implants, and thus a potential usage in dental therapy.     

牙种植高分子材料聚甲基丙烯酸甲酯的生物相容性

BACKGROUND: As a kind of dental implant material, the application of titanium has certain restrictions because of its higher probability of postoperative bleeding rate, infection and gingival hyperplasia. Studies have shown that polymethylmethacrylate has been used in artificial joints and artificial bones, but rarely reported to be used as dental implant material. OBJECTIVE: To explore the biocompatibility indexes such as cytotoxicity, cell adhesion rate, relative cell proliferation rate and post-implantation inflammatory response of human osteoblasts when pure titanium and polymethylmethacrylate are used as dental implant materials, so as to provide certain reference basis for the clinical usage of polymethylmethacrylate as the dental implant material. METHODS: Human osteoblasts were cultured in vitro. Three groups were divided as follows: control group (cells cultured normally), pure titanium group (cells cultured with titanium extract) and polymethylmethacrylate group (cells cultured with polymethylmethacrylate extract). RESULTS AND CONCLUSION: Compared with the control group, the cell adhesion rate was significantly decreased after 2, 4, 8 and 16 hours of culture with pure titanium and polymethylmethacrylate extracts (P < 0.05); the cell adhesion rate in the polymethylmethacrylate group was higher than that in the pure titanium group (P < 0.05). Compared with the control group, the cells were sparse and grew slowly after 2 days of culture with pure titanium and polymethylmethacrylate extracts. Cells in the polymethylmethacrylate group grew faster with fusiform distribution and obvious drawing phenomenon. Compared with the control group, the relative cell proliferation rate was significantly decreased after 2 days of culture with pure titanium and polymethylmethacrylate extracts (P < 0.05); the relative cell proliferation rate of polymethylmethacrylate group was higher than that of the pure titanium group (P < 0.05). The expression of inflammatory factors in rat serum was significantly increased after 7 days of implantation of titanium and polymethylmethacrylate materials (P < 0.05), the expression of inflammatory factors in the polymethylmethacrylate group was less than that in the titanium group (P < 0.05). There was only one rat developing allergic reaction, but no pyrogen reaction and no death in the polymethylmethacrylate group; and three rats presented with allergic reaction, one rat present with pyrogen reaction and no death occurred in the pure titanium group. These results demonstrate that as the dental implant material, polymethylmethacrylate is superior to pure titanium in the cell toxicity, inflammatory response and biocompatibility. 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Chitosan/bioactive glass nanoparticle composite membranes for periodontal regeneration

Barrier membranes are used in periodontal applications with the aim of supporting periodontal regeneration by physically blocking migration of epithelial cells. The present work proposes a combination of chitosan (CHT) with bioactive glass nanoparticles (BG-NPs) in order to produce a novel guided tissue and bone regeneration membrane, fabricated by solvent casting. The CHT/BG-NP nanocomposite membranes are characterized in terms of water uptake, in mechanical tests, under simulated physiological conditions and in in vitro bioactivity tests. The addition of BG-NPs to CHT membranes decreased the mechanical potential of these membranes, but on the other hand the bioactivity improved. The membranes containing the BG-NPs induced the precipitation of bone-like apatite in simulated body fluid (SBF). Biological tests were carried out using human periodontal ligament cells and human bone marrow stromal cells. CHT/BG-NP composite membranes promoted cell metabolic activity and mineralization. The results indicate that the CHT/BG-NP composite membrane could potentially be used as a temporary guided tissue regeneration membrane in periodontal regeneration, with the possibility to induce bone regeneration.     

Effect of coating thickness and its material on the stress distribution for dental implants

Dental implants have been increasingly used to recover the masticatory function of lost teeth. It has been well known that the success of a dental implant is heavily dependent on initial stability and long-term osseointegration due to optimal stress distribution in the surrounding bones by the concept implant surface coating. Hydroxyapatite (HAP), as a coating material, has been widely used in dentistry due to its biocompatibility. Some investigations show a benefit of coating dental implants with HAP, and others concluded that HAP coating reduces the long-term implant survival. Therefore, the aim of this investigation is to design a new functionally graded dental implant coating, as well as studying the effect of coating thickness on the maximum von Mises stresses in bone adjacent to the coating layer. The gradation of the elastic modulus is changed along the longitudinal direction. Stress analysis using a finite element method showed that using a coating thickness of 150 µm, functionally graded from titanium at the apex to the collagen at the root, will successfully reduce the maximum von Mises stress in bone by 19% and 17% compared to collagen and HAP coating respectively.     

Effect of coating thickness and its material on the stress distribution for dental implants

Dental implants have been increasingly used to recover the masticatory function of lost teeth. It has been well known that the success of a dental implant is heavily dependent on initial stability and long-term osseointegration due to optimal stress distribution in the surrounding bones by the concept implant surface coating. Hydroxyapatite (HAP), as a coating material, has been widely used in dentistry due to its biocompatibility. Some investigations show a benefit of coating dental implants with HAP, and others concluded that HAP coating reduces the long-term implant survival. Therefore, the aim of this investigation is to design a new functionally graded dental implant coating, as well as studying the effect of coating thickness on the maximum von Mises stresses in bone adjacent to the coating layer. The gradation of the elastic modulus is changed along the longitudinal direction. Stress analysis using a finite element method showed that using a coating thickness of 150 microm, functionally graded from titanium at the apex to the collagen at the root, will successfully reduce the maximum von Mises stress in bone by 19% and 17% compared to collagen and HAP coating respectively.     

Clinical biocompatibility of biodegradable orthopaedic implants for internal fixation: a review

When the polymeric material reaches the final stages of its degradation process, biodegradable orthopaedic fixation devices elicit a local foreign-body reaction. In most cases, the symptoms of this tissue response are subclinical and pass unnoticed, but in some patients a clinically manifest inflammatory foreign-body reaction ensues. Mild clinical reactions consist of a painful erythematous papule, those of medium severity show a sinus discharging polymeric debris for up to 6 months, and in the patients affected by a severe reaction, extensive osteolytic lesions may develop at the implant tracks. The histopathologic picture is that of a non-specific foreign-body reaction. For implants made of polyglycolide, the average incidence of the manifest reactions is 5%. When slow-degrading polymers are used, the incidence is lower. The tissue responses to polyglycolide manifest themselves 11 weeks after surgery, on an average, whereas foreign-body reactions to devices made of poly-L-lactide can emerge as late as 4 or 5 yr after the original fracture fixation operation. A poorly vascularized bone section, use of a quinone dye as an additive in the polymer, and an implant geometry with large surface area each seems to be associated with an increased risk of the occurrence of a foreign-body reaction. Yet in majority of the patients affected, no known individual marker of high risk is present. Some recent laboratory experiments indicate that it may be possible to diminish the risk of an adverse tissue response by incorporating alkaline salts or antibodies to inflammatory mediators in the implants. The results of in vitro and animal experiments, however, cannot always be directly extrapolated to humans. Only large-scale long-term clinical research will ultimately show which physico-chemical characteristics of a biodegradable orthopaedic implant provide the optimal clinical biocompatibility.     

In vivo evaluation of micro-rough and bioactive titanium dental implants using histometry and pull-out tests

We report on the in vivo histological and mechanical performance of titanium dental implants with a new surface treatment (2Step) consisting of an initial grit-blasting process to produce a micro-rough surface, followed by a combined chemical and thermal treatment that produces a potentially bioactive surface, i.e., that can form an apatitic layer when exposed to biomimetic conditions in vitro. Our aim was to assess the short- and mid-term bone regenerative potential and mechanical retention of 2Step implants in mandible and maxilla of minipigs and compare them with micro-rough grit-blasted, micro-rough acid-etched, and smooth as-machined titanium implants. The percent of bone-to-implant contact after 2, 4, 6, and 10 weeks of implantation as well as the mechanical retention after 4, and 6 weeks of implantation were evaluated with histometric and pull-out tests, respectively, as a measure of the osseointegration of the implants. We also aimed to assess the bioactive nature of 2Step surfaces in vivo. Our results demonstrated that the 2Step treatment produced micro-rough and bioactive implants that accelerated bone tissue regeneration and increased mechanical retention in the bone bed at short periods of implantation in comparison with all other implants tested. This was mostly attributed to the ability of 2Step implants to form in vivo a layer of apatitic mineral that coated the implant and could rapidly stimulate (a) bone nucleation directly on the implant surface, and (b) bone growing from the implant surface. We also proved that roughness values of Ra≈4.5 μm favoured osseointegration of dental implants at short- and mid-term healing periods, as grit-blasted implants and 2Step implants had higher retention values than as machined and acid-etched implants. The surface quality resulting from the 2Step treatment applied on cpTi provided dental implants with a unique combination of rapid bone regeneration and high mechanical retention.     

Development of a polymeric matrix metalloproteinase inhibitor as a bioactive stent coating material for prevention of restenosis

Drug-eluting stents have been developed to prevent restenosis derived from excessive growth of smooth muscle cells (SMCs) after stenting. In almost every case, however, less- or non-biocompatible polymers were selected for the platform material for impregnating drugs on the stent strut. Consideration was given principally to the physical properties of the polymers, such as their adhesion to the strut and the drug dispersibility in the polymeric matrix. In this study, we designed a matrix metalloproteinase inhibitor (MMPI)-derivatized hydrophobic polymer (PMMPI) for use as a bioactive material for stent coating. This was a copolymer of n-butylmethacrylate and a vinyl monomer of synthetic MMPI (N-Hydroxy-5-carboxyethylcarbonyloxy-2(S)-methy-4(S)-(4-phenoxybenzoyl)amino-pentanamide: ONO-M11-335) with a molecular weight of about 32,000 and MMPI content of 45 per molecule. The precursor of the MMPI monomer produced significant activity in temporally inhibiting SMC proliferation without any cellular damage. After coating with the PMMPI, adhesion and proliferation of SMCs were manifestly prevented even when a small amount of MMPI was released from the polymer. The MMPI-immobilized surface may thus be effective for inhibiting both adhesion and proliferation of SMCs, which is the first step toward in vivo experimentation. It is very much expected that coating stent struts with PMMPI containing an appropriate combination of impregnated drugs will provide a powerful tool for prevention of restenosis with little cytotoxicity.     

Effect of polyacrylic acid on the apatite formation of a bioactive ceramic in a simulated body fluid: fundamental examination of the possibility of obtaining bioactive glass-ionomer cements for orthopaedic use

Glass-ionomer cements, which consist of CaO-Al2O3-SiO2-CaF2 glass powders and a polyalkenoic acid solution, such as polyacrylic acid (PAA), have been widely used in dentistry. They set rapidly without any shrinkage, the lack of temperature increase on reaction, and develop high mechanical strength. Therefore, if bioactive glass-ionomer cements can be obtained, such cements are expected to be useful as cements for fixing orthopaedic implants to the surrounding bone. In the present study, to examine the possibility of obtaining bioactive glass-ionomer cements, the effect of PAA on the apatite formation on bioactive ceramics in a simulated body fluid was investigated. It was revealed that presence of even a small quantity of PAA inhibits the apatite formation in the body environment. It is speculated that when glass-ionomer cements are implanted into the body, PAA can be released from the glass-ionomer cements and inhibits the apatite formation on their surfaces. It is reasonable to suppose that this will occur with any glass-ionomer cement that contains PAA. Therefore, it might be considered difficult to obtain bioactive glass-ionomer cements.     

Polypropylene fumarate/phloroglucinol triglycidyl methacrylate blend for use as partially biodegradable orthopaedic cement.

Polypropylene fumarate/phloroglucinol triglycidyl methacrylate oligomeric blend-based bone cement was studied. Higher the percentage of phloroglucinol triglycidyl methacrylate, lesser the setting time. An optimum setting time could be arrived with 50:50 blend composition of the two oligomers. Composite cement of 50:50 blend prepared with hydroxyapatite granules of particle size 125 microm binds bovine rib bones. The tensile strength of this adhesive bond was found to be 1.11 kPa. The thermal studies suggest the onset of cross-linking reaction in the cured blend if the blend is heated. The absence of softening endotherm in the cured blend shows the thermosetting-like amorphous nature of blend system, which may restrict the changes in creep properties. The in vitro biodegradation studies reveal possible association of calcium ions with negatively charged units of degrading polymer chain resulting in slow down of degradation. Relatively slow degradation was observed in Ringer's solution. The study reveals the potential use of polypropylene fumarate/phloroglucinol triglycidyl methacrylate as partially degradable polymeric cement for orthopaedic applications.     

Status and potential commercial impact of stem cell-based treatments on dental and craniofacial regeneration

The projected annual demand for stem cell-based dental treatments in the United States can range from over 290 million tooth restorative treatments to 30,000 patients requiring tissue regeneration following craniofacial cancer surgery. Professional dental treatments cost Americans over $60 billion per year. Scientific advances in stem cell technologies, tissue engineering, and transplantation will provide the basis for the introduction of new treatment technologies into dentistry. This review provides an assessment of how stem cell therapies will likely change dental practice. The problems of introducing stem cell therapies are substantial, but they provide the best hope for many patients with congenital defects, and to regenerate teeth and tissues lost because of disease, cancer, and trauma, or missing because of congenital malformation. The most expensive dental treatments may be the most attractive candidates for stem cell therapies. This would indicate that craniofacial reconstruction, implants, and endodontic treatments are the most valuable applications of dental stem cell therapies, whereas tooth restorations and other dental treatments are the less commercially valuable.     

A fatigue assessment technique for modular and pre-stressed orthopaedic implants

Orthopaedic implants experience large cyclic loads, and pre-clinical analysis is conducted to ensure they can withstand millions of loading cycles. Acetabular cup developments aim to reduce wall thickness to conserve bone, and this produces high pre-stress in modular implants. As part of an implant development process, we propose a technique for preclinical fatigue strength assessment of modular implants which accounts for this mean stress, stress concentrating features and material processing.A modular cup's stress distributions were predicted computationally, under assembly and in vivo loads, and its cyclic residual stress and stress amplitude were calculated. For verification against damage initiation in low-cycle-fatigue (LCF), the peak stress was compared to the material's yield strength. For verification against failure in high-cycle-fatigue (HCF) each element's reserve factor was calculated using the conservative Soderberg infinite life criterion.Results demonstrated the importance of accounting for mean stress. The cup was predicted to experience high cyclic mean stress with low magnitude stress amplitude: a low cyclic load ratio (R_l = 0.1) produced a high cyclic stress ratio (R_s = 0.80). Furthermore the locations of highest cyclic mean stress and stress amplitude did not coincide. The minimum predicted reserve factor N_f was 1.96 (HCF) and 2.08 (LCF). If mean stress were neglected or if the stress ratio were assumed to equal the load ratio, the reserve factor would be considerably lower, potentially leading to over-engineering, reducing bone conservation.Fatigue strength evaluation is only one step in a broader development process, which should involve a series of verifications with the full range of normal and traumatic physiological loading scenarios, with representative boundary conditions and a representative environment. This study presents and justifies a fatigue analysis methodology which could be applied in early stage development to a variety of modular and pre-stressed prosthesis concepts, and is particularly relevant as implant development aims to maximise modularity and bone conservation.     

CGRP-alpha application: A potential treatment to improve osseoperception of endosseous dental implants

Dental implants have been used to restore missing teeth for several decades. However, the capacity of implants to feel the mechanical stimuli and transmit neural signals remains lower than that of natural teeth. The poor osseoperception of dental implants is due to the absence of periodontal ligaments and Ruffini-like endings as well as the secondary injury during the implant surgery and then the insufficient regeneration of damaged peripheral nerve fibers around the implants. It is a hot topic to improve the quantity and density of peripheral nerve fibers or mechanoreceptors around endosseous dental implants. Calcitonin gene-related peptide-alpha (αCGRP), a neuropeptide widely distributed throughout the central and peripheral nervous systems, is found to be upregulated in regenerating axons within injury zones and be capable of promoting local Schwann cells proliferation, which is critical for partnering during peripheral nerve regeneration. Moreover, researches show that αCGRP is a potent vasodilator and a physiologic activator of bone formation. Thus, we hypothesize that local application of αCGRP may promote peripheral nerve fibers regeneration during the bone healing progress after dental implant surgery, thus improve the osseoperception of dental implants.     

Short term in vivo biocompatibility testing of biodegradable poly(D,L-lactide)--growth factor coating for orthopaedic implants

Fracture healing can be stimulated by exogenous application of growth factors. Using porcine and rat models the efficacy of locally delivered IGF-I and TGF-beta1 from an implant coating has been demonstrated. A thin and biomechanical stable biodegradable poly(D,L-lactide) was used to coat implants and serve as a drug carrier. Due to reports of possible foreign body reactions caused by polymer materials in orthopedic surgery, this study investigated the biocompatibility of the polylactide implant coating and the locally released growth factors during the time course of rat tibial fracture healing (days 5, 10, 15, and 28 after fracture). Monocytes/macrophages and osteoclast were detected using an monoclonal antibody against ED1 (comparable to CD68 in mice and human). The antibody ED1 stains monocytes, macrophages and osteoclast in the bone marrow and in the newly formed fracture callus. A moderate density of the monocytes/macrophages was seen in the proximal part of the medullary canal, but almost no cells were detectable in the region distal to the fracture. The amount of stained cells increased during the observation time with a maximum at days 10 and 15 followed by a decrease at day 28. No differences were detectable between the investigated groups from day 5 to 15 post fracture indicating, that the used poly(D,L-lactide) or the incorporated growth factors do not evoke an elevated immunological response compared to the uncoated titanium implant at the investigated time points. A significantly higher amount of ED1 positive cells was measured 28 days after fracture in the control group compared to the groups with the coated implants. In conclusion, no indication of a foreign body reaction due to the use of the polylactide or the growth factors was found indicating a good short-term biocompatibility of this bioactive coating.