Hyaluronic acid as a bioink for extrusion-based 3D printing.

Biofabrication is enriching the tissue engineering field with new ways of producing structurally organized complex tissues. Among the numerous bioinks under investigation, hyaluronic acid (HA) and its derivatives stand out for their biological relevance, cytocompatibility, shear-thinning properties, and potential to fine-tune the desired properties with chemical modification. In this paper, we review the recent advances on bioinks containing HA. The available literature is presented based on subjects including the rheological properties in connection with printability, the chemical strategies for endowing HA with the desired properties, the clinical application, the most advanced preclinical studies, the advantages and limitations in comparison with similar biopolymer-based bioinks, and future perspectives.

Layer-by-Layer Printing of Photopolymers in 3D: How Weak is the Interface?

Additive manufacturing or, as also called, three-dimensional (3D) printing is considered as a game-changer in replacing traditional processing methods in numerous applications; yet, it has one intrinsic potential weakness related to bonding of layers formed during the printing process. Prior to finding solutions for improvement, a thorough quantitative understanding of the mechanical properties of the interface is needed. Here, a quantitative analysis of the nanomechanical properties in 3D printed photopolymers formed by digital light processing (DLP) stereolithography (SLA) is shown. Mapping of the contact Young's modulus across the layered structure is performed by atomic force microscopy (AFM) with a submicrometer resolution. The peakforce quantitative nanomechanical mapping (PF-QNM) mode was employed in the AFM experiments. The layered specimens were obtained from an acrylate-based resin (PR48, Autodesk), containing also a light-absorbing dye. We observed local depressions with values up to 30% of the maximum stiffness at the interface between the consecutively deposited layers, indicating local depletion of molecular cross-link density. The thickness values of the interfacial layers were approximately 11 µm, which corresponds to ∼22% of the total layer thickness (50 µm). We attribute this to heterogeneities of the photopolymerization reaction, related to (1) atmospheric oxygen inhibition and (2) molecular diffusion across the interface. Additionally, a pronounced stiffness decay was observed across each individual layer with a skewed profile. This behavior was rationalized by a spatial variation of the polymer cross-link density related to the variations of light absorption within the layers. This is caused by the presence of light absorbers in the printed material, resulting in a spatial decay of light intensity during photopolymerization.

Tough combinatorial poly(urethane-isocyanurate) polymer networks and hydrogels synthesized by the trimerization of mixtures of NCO-prepolymers.

The development of tough hydrogels is an essential but challenging topic in biomaterials research that has received much attention over the past years. By the combinatorial synthesis of polymer networks and hydrogels based on prepolymers with different properties, new materials with widely varying characteristics and unexpected properties may be identified. In this paper, we report on the properties of combinatorial poly(urethane-isocyanurate) (PUI) type polymer networks that were synthesized by the trimerization of mixtures of NCO-functionalized poly(ethylene glycol) (PEG), poly(propylene gylcol) (PPG), poly(ε-caprolactone) (PCL) and poly(trimethylene carbonate) (PTMC) prepolymers in solution. The resulting polymer networks showed widely varying material properties. Combinatorial PUI networks containing at least one hydrophilic PEG component showed high water uptakes of >100 wt%. The resulting hydrogels demonstrated elastic moduli of up to 10.1 MPa, ultimate tensile strengths of up to 9.8 MPa, elongation at break values of up to 624.0% and toughness values of up to 53.4 MJ m-3. These values are exceptionally high and show that combinatorial PUI hydrogels are among the toughest hydrogels reported in the literature. Also, the simple two-step synthesis and wide range of suitable starting materials make this synthesis method more versatile and widely applicable than the existing methods for synthesizing tough hydrogels. An important finding of this work is that the presence of a hydrophobic network component significantly enhances the toughness and tensile strength of the combinatorial PUI hydrogels in the hydrated state. This enhancement is the largest when the hydrophobic network component is crystallizable in nature. In fact, the PUI hydrogels containing a crystallizable hydrophobic network component are shown to be semi-crystalline in the water-swollen state. Due to their high toughness values in the water-swollen state together with their water uptake values, elastic moduli and ultimate tensile strengths, the developed hydrogels are expected to be promising materials for biomedical coating- and adhesive applications, as well as for tissue-engineering. STATEMENT OF SIGNIFICANCE: The development of tough hydrogels is a challenging topic that has received much attention over the past years. At present, double network type hydrogels are considered state-of-the-art in the field, demonstrating toughness values of several tens of MJ m-3. However, in terms of ease and versatility of the synthesis method, the possibilities are limited using a double network approach. In this work, we present combinatorial poly(urethane-isocyanurate) type polymer networks and hydrogels, synthesized by the trimerization of mixtures of NCO-functionalized prepolymers. The resulting hydrogels demonstrate exceptionally high toughness values of up to 53 MJ m-3, while the synthesis method is versatile and widely applicable. This new class of hydrogels is therefore considered highly promising in the future development of load-bearing biomaterials.

Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model.

Antibiotic-loaded biomaterials (ALBs) have emerged as a potential useful adjunctive antimicrobial measure for the prevention of infection in open fracture care. A biodegradable thermo-responsive poly(N-isopropylacrylamide) grafted hyaluronic acid (HApN) hydrogel loaded with gentamicin has recently been shown to prevent implant-related infection in a rabbit osteosynthesis model. The primary aim of this study was to determine the influence of this HApN hydrogel on bone healing at an early stage (4 weeks). A rabbit humeral osteotomy model with plating osteosynthesis was used to compare fracture healing in rabbits receiving the hydrogel as compared with control animals. The secondary aim was to observe fracture healing in groups treated with and without antibiotic-loaded hydrogel in the presence of bacterial contamination. In all groups, outcome measures were mechanical stability and histological score, with additional quantitative bacteriology in the inoculated groups. Application of the HApN hydrogel in non-inoculated rabbits did not significantly influence humeral stiffness or histological scores for fracture healing in comparison to controls. In the inoculated groups, animals receiving the bacterial inoculum without hydrogel were culture-positive at euthanasia and found to display lower humeral stiffness values and higher histopathological scores for bacterial presence in comparison with equivalents receiving the gentamicin-loaded HApN hydrogel, which were also infection-free. In summary, our data showed that HApN was an effective antibiotic carrier that did not affect fracture healing. This data supported its suitability for application in fracture care. Addition of osteopromotive compounds could provide further support for accelerating fracture healing in addition to successful infection prophylaxis.

Poly(trimethylene carbonate) and poly(D,L-lactic acid) modify human dendritic cell responses to staphylococci but do not affect Th1 and Th2 cell development.

Biomaterial-associated infections (BAIs) are frequent complications in the use of medical devices (biomaterials) correlated with considerable patient discomfort and high treatment costs. The presence of a biomaterial in the host causes derangement of local immune responses increasing susceptibility to infection. Dendritic cells (DCs) have an important role in directing the nature of immune responses by activating and controlling CD4+ T helper (Th) cell responses. To assess the immunomodulatory effect of the combined presence of biomaterials and Staphylococcus aureus (S. aureus) or Staphylococcus epidermidis (S. epidermidis), DC-mediated T cell proliferation and Th1/Th2 cell development were measured using an in vitro human cell system. Poly(trimethylene carbonate) (PTMC) and poly(D,L-lactic acid) (PDLLA) modified the production of the DC pro-inflammatory cytokines TNF-α, IL-6 and IL-23 in response to S. aureus and S. epidermidis. However, this modified cytokine production did not cause differences in Th1/Th2 cell polarisation, showing a Th1 cell predominance. In the absence of staphylococci, neither of the biomaterials induced DC-mediated T cell proliferation or Th1/Th2 cell polarisation. Moreover, either in the absence or presence of the biomaterials, S. aureus was a more potent inducer of DC cytokine secretion, T cell proliferation and Th1 cell development than S. epidermidis. In conclusion, although PTMC and PDLLA modulated DC cytokine responses to staphylococci, this did not alter the resulting Th cell development. This result suggested that, in this human cell model, Th1/Th2 cell responses were mainly determined by the species of bacteria and that PTMC or PDLLA did not detectably influence these responses.

Drug delivery systems functionalized with bone mineral seeking agents for bone targeted therapeutics.

The systemic administration of drugs to treat bone diseases is often associated with poor uptake of the drug in the targeted tissue, potential systemic toxicity and suboptimal efficacy. In order to overcome these limitations, many micro- and nano-sized drug carriers have been developed for the treatment of bone pathologies that exhibit specific affinity for bone. Drug carriers can be functionalized with bone mineral seekers (BMS), creating a targeted drug delivery system (DDS) which is able to bind to bone and release therapeutics directly at the site of interest. This class of advanced DDS is of tremendous interest due to their strong affinity to bone, with great expectation to treat life-threatening bone disorders such as osteomyelitis, osteosarcoma or even osteoporosis. In this review, we first explain the mechanisms behind the affinity of several well-known BMS to bone, and then we present several effective approaches allowing the incorporation BMS into advanced DDS. Finally, we report the therapeutic applications of BMS based DDS under development or already established. Understanding the mechanisms behind the biological activity of recently developed BMS and their integration into advanced therapeutic delivery systems are essential prerequisites for further development of bone-targeting therapies with optimal efficacy.

Surface-enrichment with hydroxyapatite nanoparticles in stereolithography-fabricated composite polymer scaffolds promotes bone repair.

Fabrication of composite scaffolds using stereolithography (SLA) for bone tissue engineering has shown great promises. However, in order to trigger effective bone formation and implant integration, exogenous growth factors are commonly combined to scaffold materials. In this study, we fabricated biodegradable composite scaffolds using SLA and endowed them with osteopromotive properties in the absence of biologics. First we prepared photo-crosslinkable poly(trimethylene carbonate) (PTMC) resins containing 20 and 40wt% of hydroxyapatite (HA) nanoparticles and fabricated scaffolds with controlled macro-architecture. Then, we conducted experiments to investigate how the incorporation of HA in photo-crosslinked PTMC matrices improved human bone marrow stem cells osteogenic differentiation in vitro and kinetic of bone healing in vivo. We observed that bone regeneration was significantly improved using composite scaffolds containing as low as 20wt% of HA, along with difference in terms of osteogenesis and degree of implant osseointegration. Further investigations revealed that SLA process was responsible for the formation of a rich microscale layer of HA corralling scaffolds. To summarize, this work is of substantial importance as it shows how the fabrication of hierarchical biomaterials via surface-enrichment of functional HA nanoparticles in composite polymer stereolithographic structures could impact in vitro and in vivo osteogenesis. STATEMENT OF SIGNIFICANCE: This study reports for the first time the enhance osteopromotion of composite biomaterials, with controlled macro-architecture and microscale distribution of hydroxyapatite particles, manufactured by stereolithography. In this process, the hydroxyapatite particles are not only embedded into an erodible polymer matrix, as reported so far in the literature, but concentrated at the surface of the structures. This leads to robust in vivo bone formation at low concentration of hydroxyapatite. The reported 3D self-corralling composite architecture provides significant opportunities to develop functional biomaterials for bone repair and tissue engineering.

Evaluation of novel biodegradable three-armed- and hyper-branched tissue adhesives in a meniscus explant model.

Current treatment methods to repair meniscal tears do not bring fully satisfactory results. Tissue adhesives are considered promising alternatives, since they are easy to apply and cause minimal tissue trauma. The first aim of this study was to analyze the adhesive properties of and tissue response to two recently developed biodegradable block copolymeric three-armed- and hyper-branched tissue adhesives. The second aim was to investigate if tissue surface modification with collagenase improves the attachment of the adhesives and increases the healing potential of the tissue. Cylindrical explants were harvested from bovine menisci. The central core of the explants was removed and glued back into the defect, with or without incubation in collagenase solution prior to gluing, using one of the novel glues, Dermabond® or fibrin glue. The repair constructs were cultured in vitro for 1 and 28 days. Adhesion tests and histology were performed to analyze the effects of the glue in combination with the additional treatment. The adhesive strength of the novel glues was 40-50 kPa, which was significantly higher than that of fibrin glue (15 kPa). Cells were present in direct contact with the glues, and the tissue remained vital during the whole culture period. Increased cellularity around the tear in the collagenase treated explants was observed after 1 day. The two newly developed tissue adhesives are attractive materials to be used for repair of meniscal tears. The beneficial influence of collagenase treatment in treating meniscal tears with glues still needs to be confirmed in more clinical relevant studies. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1405-1411, 2017.

Tissue adhesives for meniscus tear repair: an overview of current advances and prospects for future clinical solutions.

Menisci are crucial structures in the knee joint as they play important functions in load transfer, maintaining joint stability and in homeostasis of articular cartilage. Unfortunately, ones of the most frequently occurring knee injuries are meniscal tears. Particularly tears in the avascular zone of the meniscus usually do not heal spontaneously and lead to pain, swelling and locking of the knee joint. Eventually, after a (partial) meniscectomy, they will lead to osteoarthritis. Current treatment modalities to repair tears and by that restore the integrity of the native meniscus still carry their drawbacks and a new robust solution is desired. A strong tissue adhesive could provide such a solution and could potentially improve on sutures, which are the current gold standard. Moreover, a glue could serve as a carrier for biological compounds known to enhance tissue healing. Only few tissue adhesives, e.g., Dermabond(®) and fibrin glue, are already successfully used in clinical practice for other applications, but are not considered suitable for gluing meniscus tissue due to their sub-optimal mechanical properties or toxicity. There is a growing interest and research field focusing on the development of novel polymer-based tissue adhesives, but up to now, there is no material specially designed for the repair of meniscal tears. In this review, we discuss the current clinical gold standard treatment of meniscal tears and present an overview of new developments in this field. Moreover, we discuss the properties of different tissue adhesives for their potential use in meniscal tear repair. Finally, we formulate recommendations regarding the design criteria of material properties and adhesive strength for clinically applicable glues for meniscal tears.

Development of biodegradable hyper-branched tissue adhesives for the repair of meniscus tears.

Meniscus tears are one of the most commonly occurring injuries of the knee joint. Current meniscus repair techniques are challenging and do not bring fully satisfactory results. Tissue adhesives are a promising alternative, since they are easy to apply and cause minimal tissue trauma. In this study, a series of amphiphilic copolymers based on polyethylene glycol, trimethylene carbonate and citric acid were synthesized and subsequently end-functionalized with hexamethylene diisocyanate to form reactive adhesive materials. The shear adhesive strength of the networks to bovine meniscus tissue measured in a lap-shear adhesion test ranged between 20 and 80 kPa, which was better than for fibrin glue (10 kPa). The elastic modulus of the networks depended on composition and was in the same range as that of human meniscus. Cell compatibility was assessed using Alamar Blue staining after incubation of the bovine meniscus cells with different concentrations of the glues for 7 days. Cell viability was not affected after adding up to 3mg of the adhesive/mL of medium. The proposed materials are suitable candidates to be used as resorbable tissue adhesives for meniscus repair. They have excellent mechanical and adhesive properties that can be adjusted by varying the composition of the copolymers. STATEMENT OF SIGNIFICANCE: Meniscal tears often occur and current treatment strategies do not bring fully satisfactory results. Use of biodegradable tissue adhesives would be an interesting option, but currently available adhesives are not suited due to toxicity or poor mechanical properties. Here, we describe the development of novel biodegradable, hyper-branched, adhesive copolymers. These adhesives cure upon contact with water forming flexible networks. Their adhesion to bovine meniscus tissue was significantly better than that of clinically used fibrin glue. The tensile properties of the cured networks were in the same range of values of the human meniscus. When physiologically relevant amounts were added to cells in culture, not toxic effects were observed. Therefore, the proposed materials are interesting resorbable tissue adhesives for meniscus repair.

Preparation of gentamicin dioctyl sulfosuccinate loaded poly(trimethylene carbonate) matrices intended for the treatment of orthopaedic infections.

BACKGROUND: Infection is a common problem in trauma and orthopaedic surgery. Antibiotic-loaded biomaterials are used locally to clear infections as an adjunct to systemic antibiotics. Gentamicin-sulphate (GEN-SULPH) is commonly used in antibiotic-loaded biomaterials, although it displays high water solubility resulting in quick diffusion from the carrier. OBJECTIVE: Preparation of a lipophilic derivative of gentamicin to reduce solubility and obtain a slower release. Subsequently, entrapment of this lipophilic gentamicin within poly(trimethylene carbonate) (PTMC) matrices. METHODS: Hydrophobic ion-pairing was used to prepare lipophilic gentamicin (GEN-AOT). The susceptibility of Staphylococcus aureus NCTC 12973 and Staphylococcus epidermidis 103.1 for GEN-AOT was tested and the viability of fibroblasts upon exposure to GEN-AOT was assessed. GEN-AOT was then loaded into PTMC films. RESULTS: GEN-AOT was successfully prepared as confirmed by FTIR-spectroscopy. GEN-AOT was bactericidal for S. epidermidis and S. aureus at 0.5 µM and 8.5 µM, respectively. At 1.1 µM GEN-AOT no reduction in fibroblast viability was observed. At 11 µM the reduction was ∼50% . PTMC discs loaded with GEN-AOT were prepared by compression molding. CONCLUSIONS: Lipophilic GEN-AOT was at least as potent as GEN-SULPH. For S. epidermidis it was even more potent than GEN-SULPH. More than 50% fibroblast cell viability was maintained at bactericidal concentration for both bacterial strains.

Delivery systems for the treatment of degenerated intervertebral discs.

The intervertebral disc (IVD) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production, abnormal enzyme activities and production of pro-inflammatory substances like cytokines. The established treatment strategy for IVD degeneration consists of physiotherapy, pain medication by drug therapy and if necessary surgery. This approach, however, has shown limited success. Alternative strategies to increase and prolong the effects of bioactive agents and to reverse the process of IVD degeneration include the use of delivery systems for drugs, proteins, cells and genes. In view of the specific anatomy and physiology of the IVD and depending on the strategy of the therapy, different delivery systems have been developed which are reviewed in this article.

Poly(trimethylene carbonate) and biphasic calcium phosphate composites for orbital floor reconstruction: a feasibility study in sheep.

In the treatment of orbital floor fractures, bone is ideally regenerated. The materials currently used for orbital floor reconstruction do not lead to the regeneration of bone. Our objective was to render polymeric materials based on poly(trimethylene carbonate) (PTMC) osteoinductive, and to evaluate their suitability for use in orbital floor reconstruction. For this purpose, osteoinductive biphasic calcium phosphate (BCP) particles were introduced into a polymeric PTMC matrix. Composite sheets containing 50 wt% BCP particles were prepared. Also laminates with poly(D,L-lactide) (PDLLA) were prepared by compression moulding PDLLA films onto the composite sheets. After sterilisation by gamma irradiation, the sheets were used to reconstruct surgically-created orbital floor defects in sheep. The bone inducing potential of the different implants was assessed upon intramuscular implantation. The performance of the implants in orbital floor reconstruction was assessed by cone beam computed tomography (CBCT). Histological evaluation revealed that in the orbital and intramuscular implantations of BCP containing specimens, bone formation could be seen after 3 and 9 months. Analysis of the CBCT scans showed that the composite PTMC sheets and the laminated composite sheets performed well in orbital floor reconstruction. It is concluded that PTMC/BCP composites and PTMC/BCP composites laminated with PDLLA have osteoinductive properties and seem suitable for use in orbital floor reconstruction.

Challenges and strategies in the repair of ruptured annulus fibrosus.

Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell- and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review.

Preparation of designed poly(D,L-lactide)/nanosized hydroxyapatite composite structures by stereolithography.

The preparation of scaffolds to facilitate the replacement of damaged tissues and organs by means of tissue engineering has been much investigated. The key properties of the biomaterials used to prepare such scaffolds include biodegradability, biocompatibility and a well-defined three-dimensional 3-Dpore network structure. In this study a poly(D,L-lactide)/nanosized hydroxyapatite (PDLLA/nano-Hap) composite resin was prepared and used to fabricate composite films and computer designed porous scaffolds by micro-stereolithography, mixing varying quantities of nano-Hap powder and a liquid photoinitiator into a photo-crosslinkable PDLLA-diacrylate resin. The influence of nano-Hap on the rheological and photochemical properties of the resins was investigated, the materials being characterized with respect to their mechanical, thermal and morphological properties after post-preparation curing. In the cured composites stiffness was observed to increase with increasing concentration of nanoparticles. A computer designed construct with a pore network based on the Schwarz architecture was fabricated by stereolithography using PDLLA/nano-Hap composite resins.

Flexible, elastic and tear-resistant networks prepared by photo-crosslinking poly(trimethylene carbonate) macromers.

Poly(trimethylene carbonate) (PTMC) macromers with molecular weights (M(n)) between 1000 and 41,000 g mol(-1) were prepared by ring opening polymerization and subsequent functionalization with methacrylate end groups. Flexible networks were obtained by radical photo-crosslinking reactions of these macromers. With increasing molecular weight of the macromer the networks obtained showed increasing swelling ratios in chloroform and decreasing glass transition temperatures, reaching a constant value of approximately -18°C, which is close to that of linear high molecular weight PTMC. For all prepared networks the creep resistance was high. However, the molecular weight of the macromer strongly influenced the tensile properties of the networks. With increasing molecular weight of the macromer the E-modulus of the networks decreased from 314 MPa (lowest M(n)) to 5 MPa (highest M(n)), while their elongation at break continuously increased, reaching a very high value of 1200%. The maximum tensile strength values of the networks were found to first decrease with increasing M(n), but to increase again at values above approximately 10,000gmol(-1), at which the networks started to show rubber-like behavior. The toughness (area under the stress-strain curves, W) determined in tensile testing experiments, in tear propagation experiments, and in suture retention strength measurements showed that PTMC networks prepared from the higher molecular weight macromers (M(n)>10,000 g mol(-1)) were tenacious materials. The mechanical properties of these networks compare favorably with those of linear high molecular weight PTMC and well-known elastomeric materials like silicone rubber (poly(dimethylsiloxane)) and natural latex rubber. Additionally they also compare well with those of native blood vessels, which may be of importance in the use of these materials for the tissue engineering of small diameter blood vessels.

In vivo behaviour of a biodegradable poly(trimethylene carbonate) barrier membrane: a histological study in rats.

The aim of the present study was to evaluate the response of surrounding tissues to newly developed poly(trimethylene carbonate) (PTMC) membranes. Furthermore, the tissue formation beneath and the space maintaining properties of the PTMC membrane were evaluated. Results were compared with a collagen membrane (Geistlich BioGide), which served as control. Single-sided standardized 5.0 mm circular bicortical defects were created in the mandibular angle of rats. Defects were covered with either the PTMC membrane or a collagen membrane. After 2, 4 and 12 weeks rats were sacrificed and histology was performed. The PTMC membranes induced a mild tissue reaction corresponding to a normal foreign body reaction. The PTMC membranes showed minimal cellular capsule formation and showed signs of a surface erosion process. Bone tissue formed beneath the PTMC membranes comparable to that beneath the collagen membranes. The space maintaining properties of the PTMC membranes were superior to those of the collagen membrane. Newly developed PTMC membranes can be used with success as barrier membranes in critical size rat mandibular defects.

Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes.

The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague-Dawley rats, a standardized 5.0mm circular defect was created in the left mandibular angle. New bone formation was demonstrated by post mortem micro-radiography, micro-computed tomography imaging and histological analysis. Four groups (control, PTMC, collagen, e-PTFE) were evaluated at three time intervals (2, 4 and 12 weeks). In the membrane groups the defects were covered; in the control group the defects were left uncovered. Data were analysed using a multiple regression model. In contrast to uncovered mandibular defects, substantial bone healing was observed in defects covered with a barrier membrane. In the latter case, the formation of bone was progressive over 12 weeks. No statistically significant differences between the amount of new bone formed under the PTMC membranes and the amount of bone formed under the collagen and e-PTFE membranes were observed. Therefore, it can be concluded that PTMC membranes are well suited for use in guided bone regeneration.

Tissue engineering of small-diameter vascular grafts: a literature review.

For the treatment of cardiovascular disease, functional arterial blood vessel prostheses with an inner diameter less than 6 mm are needed. This article gives an overview of the preparation of such vascular grafts by means of tissue engineering.