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Biomedical subjects

M Kellomäki

Publications and source records attributed to M Kellomäki.

At least 19 recordsLinked to original sources

A histological and immunohistochemical study of tissue reactions to solid poly(ortho ester) in rabbits.

In many cases only the temporary presence of a biomaterial is needed in tissue support, augmentation or replacement. In such cases biodegradable materials are better alternatives than biostable ones. At present, biodegradable polymers are widely used in the field of maxillofacial surgery as sutures, fracture fixation devices and as absorbable membranes. The most often used polymers are aliphatic polyesters, such as polyglycolic acid (PGA) and polylactic acid (PLA). Poly(ortho ester) is a surface eroding polymer, which has been under development since 1970, but is used mostly in drug delivery systems in semisolid form. The aim of this study was to evaluate the tissue reactions of solid poly(ortho ester) (POE), histologically and immunohistochemically. Resorption times and the effect of 2 different sterilization methods (gamma radiation and ethylene oxide) upon resorption were also evaluated. Material was implanted into the tibia and subcutaneously into the mandibular ramus area of 24 rabbits. Follow-up times were 1-10, 14 and 24 weeks. Histological studies showed that POE induces a moderate inflammation in soft tissue and in bone. At 24 week follow-up, inflammation was mild in soft tissue and moderate in bone. In immunohistochemical studies, no highly fluorescent layer of tenascin or fibronectin was found adjacent to the implant. Resorption of gamma-sterilized rods was faster than ethylene oxide-sterilized rods. The total resorption time was more than 24 weeks in both groups. Clinically the healing was uneventful and the implants the well tolerated by the living tissue. This encourages these authors to continue studies with this interesting new material to search for the ideal material for bone filling and fracture fixation.

Absorbable Implants↗

Characterization of human primary osteoblast response on bioactive glass (BaG 13-93)- coated poly-L,DL-lactide (SR-PLA70) surface in vitro.

Bioabsorbable polylactide-based polymers are commonly used for bone reconstruction. Although these polymers have proven successful in many applications, they do not have the capacity to induce osteoconduction. Therefore, several strategies have been developed to manufacture osteoconductive polylactide-based composites. In this study, we have investigated in vitro response of human primary osteoblasts for self-reinforced poly-L,DL-lactide 70/30 (SR-PLA70) plates coated with spheres of bioactive glass 13-93 (SR-PLA70 + BaG). Osteoblasts were cultured on SR-PLA70 and SR-PLA70 + BaG plates for 2, 7, or 14 days. By day 7, both materials induced a reduction in total cell population. However, by day 14 the proliferative response of osteoblasts on SR-PLA70 + BaG surface was such that the cell population had regained similar levels as that of day 2 controls. Alkaline phosphatase activity was higher on SR-PLA70 at day 7 but declined to control levels by day 14. There were no significant time-dependent variations in alkaline phosphatase activity on SR-PLA70 + BaG. After in vitro hydrolysis for 7 days, the elemental analysis of SR-PLA70 + BaG surface showed the presence of mineral precipitates that were confirmed as crystalline hydroxyapatite. This was accompanied by osteoblast spreading, protrusions of microvilli adhered to BaG 19-39 surface, cuboidal phenotype and cell surface associated formation of hydroxyapatite microspheres. In conclusion, the SR-PLA70 + BaG composite is capable of inducing a proliferative response of human primary osteoblasts, and appears to support the development of mature osteoblast phenotype. Therefore, the SR-PLA70 + BaG composites appear as promising osteoconductive scaffold candidates for reconstruction and regeneration of bone matrix.

Cell Adhesion↗

The copolymer of epsilon-caprolactone-lactide and tricalcium phosphate does not enhance bone growth in mandibular defect of sheep.

In the field of craniomaxillofacial and orthopaedic surgery there is a constant need for bone or bone substitute. At the present, the most effective way to enhance bone healing clinically is to use autogenous bone grafts. The problems associated with the use of these autografts are donor site morbidity, limited supply and need for a second operative site. Currently there are several different synthetic products commercially available in the market; nevertheless, none of them is ideal for filling bone defects. Therefore, search for new synthetic materials for bone replacement is necessary. A mixture of tricalcium phosphate (TCP) and epsilon-caprolactone-lactide copolymer P(epsilon -CL/DL-LA) was prepared and implanted in critical size mandibular bone defects in twelve sheep. Contralateral side was used as a control. Follow-up times for histological and radiological studies were 9, 14, 24 and 52 weeks. We found that the implanted material did not enhance bone formation compared to control site. We also confirmed that defect size was of critical size, since there was no complete healing of the control site either. The results do not encourage us to continue our studies with the mixture of TCP and P(epsilon-CL/DL-LA) as a filling material for bone defects. Therefore the search for the ideal material is still ongoing.

Animals↗

Material and knot properties of braided polyester (Ticron) and bioabsorbable poly-L/D-lactide (PLDLA) 96/4 sutures.

The purpose of the present study was to investigate in vitro the biomechanical material and knot properties and histomorphometrical knot properties of 3-0 braided polyester suture (Ticron) and bioabsorbable poly-L/D-lactide (PLDLA) 96/4 suture. In Ticron five throws are needed to form a secure knot, and the 1 = 1 = 1 = 1 = 1 and the 2 = 1 = 1 = 1 configurations are recommended. For PLDLA several granny and square knots formed a secure knot, but the 1 = 1 and 1 = 1 = 1 knots were the best. These PLDLA knots had lower yield force and strain at yield point, but higher stiffness than the recommended Ticron knots. The ultimate force values did not differ, but PLDLA knots had significantly higher strain at ultimate point. In the histomorphometrical analysis of the recommended knots, the PLDLA knots had a significantly smaller knot surface area than the Ticron knots. According to these results, PLDLA suture proved to be suitable for flexor tendon repair.

Absorbable Implants↗

A novel bioabsorbable composite membrane of Polyactive 70/30 and bioactive glass number 13--93 in repair of experimental maxillary alveolar cleft defects.

A novel bioabsorbable composite membrane of polyethylene oxide terephthalate and polybutylene terephthalate copolymer (Polyactive 70/30) combined with bioactive glass No. 13--93 was tested in the repair of experimental maxillary alveolar cleft defects. In this pilot study, the possible ability of the membrane to promote bone formation by guided tissue regeneration was investigated. Standard alveolar defects were made bilaterally in the maxilla of 12 growing rabbits and were filled with autogenous bone grafts. The test defect was covered with the composite membrane and the other defect was left uncovered to serve as a control. The follow-up time was 10 weeks. Radiological, histological, and histomorphometric evaluations were performed. Radiologically, no statistically significant differences between test and control defects at 10 weeks were found. Histologically, the membrane enhanced osteogenic activity locally at the membrane-bone interface. Swelling of the membrane was observed. Histomorphometrically, no significant promotion of bone formation by the membrane was observed. The composite membrane was found to be biocompatible and surgically easy to use, but its osteopromotive effect was limited in this experimental cleft model. Further studies are necessary to assess its suitability for reconstructive surgical applications.

Alveolar Process↗

In vitro properties of PLLA screws and novel bioabsorbable implant with elastic nucleus to replace intervertebral disc.

The suitability of two different implant types for the replacement of the intervertebral disc was studied in vitro. Self-reinforced poly-L-lactide (SR-PLLA) screws Ø 4.5 mm were studied 24 weeks in vitro and cylindrical implants with elastic nucleus made of poly(L/D)lactide 96/4, poly(L/DL)lactide 70/30, Bioactive Glass n:o 13-93 and Polyactive 1000PEOT70PBT30 were studied 15 weeks in vitro. The cylindrical implant mimics the size and shape of the intervertebral disc. During the in vitro, there were no changes in compression properties with either implant types. The screws had sufficient modulus for intervertebral ossification in the canine model and the cylindrical implant showed also sufficient mechanical properties. These results suggest that both implant types could be used in clinical testing.

Absorbable Implants↗

Tyrosine derived polycarbonate membrane is useful for guided bone regeneration in rabbit mandibular defects.

Standardized bilateral through-and-through defects (12x6 mm) were created extraorally in the mandibular angle of 18 New Zealand White rabbits. Animals were divided in to three groups (n=6) according to the intended healing time. On the left side, defects were covered with a poly(desaminotyrosyl-tyrosine-ethyl ester carbonate) (PDTE carbonate) membrane wrapped around the inferior border of the mandible and fixed with bioabsorbable sutures. On the right side, the defects were filled with a mesh made of bioactive glass 13-93 and 3 wt% chitosan. The defects were covered with the same membranes. Periosteal flap was sutured over the membrane. Radiographically, bone ingrowth was seen in all specimens at 12 weeks postoperatively. At 24 weeks, completely ossified area remained approximately at the same level as at 12 weeks, but the non-ossified area decreased to almost zero. However, the bioactive glass mesh did not improve the results. Nevertheless, enveloping the defect with PDTE carbonate membrane seemed to play a crucial role in new bone formation. Based on these results, we conclude that tyrosine polycarbonate is a promising new material for guided bone regeneration.

Animals↗

Self-reinforced composites of bioabsorbable polymer and bioactive glass with different bioactive glass contents. Part I: Initial mechanical properties and bioactivity.

Spherical bioactive glass 13-93 particles, with a particle size distribution of 50-125 microm, were combined with bioabsorbable poly-L,DL-lactide 70/30 using twin-screw extrusion. The composite rods containing 0, 20, 30, 40 and 50 wt% of bioactive glass were further self-reinforced by drawing to a diameter of approximately 3 mm. The bioactive glass spheres were well dispersed and the open pores were formed on the composite surface during drawing. The initial mechanical properties were studied. The addition of bioactive glass reduced the bending strength, bending modulus, shear strength, compression strength and torsion strength of poly-L,DL-lactide. However, the strain at maximum bending load increased in self-reinforced composites. Initially brittle composites became ductile in self-reinforcing. The bioactivity was studied in phosphate buffered saline for up to 12 days. The formation of calcium phosphate precipitation was followed using scanning electron microscopy and energy dispersive X-ray analysis. Results showed that the bioactive glass addition affected the initial mechanical properties and bioactivity of the composites. It was concluded that the optimal bioactive glass content depends on the applications of the composites.

Biocompatible Materials↗

Orbital floor reconstruction with poly-L/D-lactide implants: clinical, radiological and immunohistochemical study in sheep.

In this study the reconstruction capacity of orbital wall in sheep was evaluated when poly-L/D-lactide (PLDLA96) implants were used for large blow-out defects in 18 sheep. The contralateral side, where the defects healed spontaneously, served as controls. The follow-up was 12, 16, 22 and 36 weeks. Healing was evaluated clinically, radiologically, histologically and immunohistochemically. Physiochemical properties of the implants were also studied. At first, the implants were surrounded by elastic capsules, which gradually ossified. At 36 weeks, 60% were still visible and deformed but surrounded by bone. Light microscopy revealed a low grade inflammatory reaction. Expression of Tn-c and cFn was intense throughout the study. Shear strength decreased gradually and was not measurable after 16 weeks. Crystallinity increased steadily from 1.5 to 29.30% and molecular weight decreased from 49,000 to 4186. In CT, the final bony defect was smaller in the reconstructed sides than in the controls. Based on this study it can be concluded that PLDLA96 implant provokes a local inflammation, which does not prevent bone healing. The deformation of the implant, however, indicates that this PLDLA96 plate is not suitable for orbital floor reconstruction.

Absorbable Implants↗

A comparative analysis of the biomechanical behaviour of five flexor tendon core sutures.

Five core suture techniques were compared by static tensile testing in vitro. Fifty porcine tendons were used. The core sutures were performed with 3-0 or 4-0 braided polyester suture (Ticron) and the over-and-over running peripheral sutures with 6-0 monofilament polypropylene (Prolene). The core sutures were: (1) Pennington modified Kessler (3-0), (2) Double Pennington modified Kessler (3-0), (3) 4-strand Savage (3-0), (4) 4-strand Savage (4-0), and (5) 6-strand Savage (4-0). Repairs were compared as paired in regard to one variable: the number of core suture strands, the suture calibre, or the suture configuration. Biomechanical differences between the repair groups started during the linear region, with the yield force and stiffness increasing along with the number of core suture strands. All three variables influenced the strain at the yield point. Thus, the strength of the intact repair can be improved by modifying the core suture. In all repairs gap formation started near the yield point after failure of the peripheral suture. The yield force represents the strength of the intact repair composite and should be considered the strength of the tendon repair.

Animals↗

Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats.

Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.

Animals↗

Bioreconstructive joint scaffold implant arthroplasty in metacarpophalangeal joints: short-term results of a new treatment concept in rheumatoid arthritis patients.

Swanson silicone implant is the "gold standard" of metacarpophalangeal joint reconstruction in rheumatoid arthritis (RA) patients. However, durability problems of silicone implants have led us to develop a new technique based on bioreconstructive implants. PLA96 (poly-L,D-lactide copolymer, L:D ratio of 96:4) scaffolds were engineered. Bioabsorption and substitution of porous PLA96 scaffold with living tissue eventually produce a neojoint. In the current prospective study, 23 RA patients (80 joints) were operated on, using PLA96 implants. Fifteen patients (54 joints) have been monitored for at least 1 year. Pain alleviation was well achieved. Range of motion improvement was emphasized to extension direction of functional arc. The average ulnar deviation was preoperatively 26 degrees, and at follow-up it was 6 degrees. Volar subluxation was noticeable in 56% of joints preoperatively and in 6% at 1-year follow-up. This is the first report of the formation of a living, functional joint in situ by means of a synthetic bioreconstructive joint scaffold. Results of this preliminary short-term study are comparable with previously published data on silicone arthroplasty. However, bioreconstructive prostheses can aid in preventing problems that occur with biostable prostheses. Tissue engineering has created a new era in the reconstruction of damaged joints.

Arthritis, Rheumatoid↗

In vitro degradation of Polyactive 1000PEOT70PBT30 devices.

Polyactive 1000PEOT70PBT30 (a segmented block copolymer of poly(ethylene oxide terephtalate)/poly(butylene terephtalate) with 70/30 PEOT/PBT ratio) was processed into three different types of samples: injection molded to rods, hot-pressed to films and to composite membranes made by hot-pressing a tubular mesh of poly-L,D-lactide 96/4 between two films of Polyactive. The molecular weight of Polyactive was not influenced by processing, but gamma-sterilization seemed to increase the weight average molecular weight (Mw). Mechanical properties of the rods and films decreased rapidly in hydrolytic conditions due to the hydrogel nature of the polymer, swelling and degradation. Mesh reinforcement increased the mechanical properties, but the components separated during soaking. In vitro the molecular weight of the rods and films started to decrease immediately, but the PEOT (or PEO) proportion remained relatively constant for 26 weeks. Macroscopically, all the wet devices remained intact, but fragmented on drying. Microscopically, topographical formations of polymer were found on the surfaces and small sodium-rich spots were precipitated onto and inside the polymer. Thermal measurements showed that polymer consisted of amorphous PEOT segments and both amorphous and crystalline PBT segments.

Biodegradation, Environmental↗

Effect of filler content on mechanical and dynamic mechanical properties of particulate biphasic calcium phosphate--polylactide composites.

A bioabsorbable self-reinforced polylactide/biphasic calcium phosphate (BCP) composite is being developed for fracture fixation plates. One manufacturing route is to produce preimpregnated sheets by pulling polylactide (PLA) fibres through a suspension of BCP filler in a PLA solution and compression moulding the prepreg to the desired shape. To aid understanding of the process, interactions between the matrix and filler were investigated. Composite films containing 0-0.25 volume fraction filler, produced by solvent casting, were analysed using SEM, tensile testing and dynamic mechanical analysis (DMA). Homogeneous films could be made, although some particle agglomeration was seen at higher filler volume fractions. As the filler content increased, the failure strain decreased due to a reduction in the amount of ductile polymer present and the ultimate tensile strength (UTS) decreased because of agglomeration and void formation at higher filler content. The matrix glass transition temperature increased due to polymer chain adsorption and immobilization onto the BCP particles. Complex damping mechanisms, such as particle-particle agglomeration, may exist at the higher BCP volume fractions.

Algorithms↗

Dynamic mechanical characterization of biodegradable composites of hydroxyapatite and polylactides.

The thermo-mechanical analysis of some novel, totally bioactive, three-component composite systems intended for the repair and augmentation of bone has been performed. The composites are composed of hydroxyapatite (HA), particulate reinforced biodegradable polylactic acid (PDLLA), with a second reinforcing phase of semi-crystalline, unidirectional fibers of polylactic acid (PLLA) homopolymer. Dynamic mechanical analysis (DMA) applied small-strain cyclic deformations to simulate physiological loading. The effect of the two fillers on the glass transition temperature of the matrix (Tg-PDLLA) and on the viscoelastic parameters, storage modulus (EI), and tan delta were analyzed. Thermal characterization with differential scanning calorimetry (DSC) was compared to the DMA data. It was established that the addition of HA and/or PLLA fibers increased EI, both below and above Tg-PDLLA. The combination of both reinforcing agents was the most effective. The damping was reduced with the addition of HA alone and in combination with PLLA fibers. Tg-PDLLA was increased by the addition of HA, PLLA fibers, and the combination of the two reinforcing agents. The magnitude of the increase in Tg-PDLLA was similar for both types of reinforcement.

Biocompatible Materials↗

Inability of transforming growth factor-beta 1, combined with a bioabsorbable polymer paste, to promote healing of bone defects in the rat distal femur.

The ability of transforming growth factor-beta 1 (TGF-beta 1) to promote bone formation suggests that it may have potential as a therapeutic agent in bone defects. However, there still exists a need for an effective method of delivering TGF-beta 1 to the site of an osseous defect. In the present study, TGF-beta 1 was embedded in a bioabsorbable polymer paste (a blend of an L-lactide oligomer and a copolymer of epsilon-caprolactone and DL-lactide). The release of TGF-beta 1 from the polymer paste was examined in vitro with an enzyme-linked immunosorbent assay, which showed sustained release of active TGF-beta 1 over a 7-day period. Further, the polymer paste was used to fill a bone defect in the rat distal femur. The amount of TGF-beta 1 per rat was 50 micrograms, while in a control group we used an identical polymer paste without the growth factor. After a follow-up of 1 week and 3 weeks, the femurs were examined radiographically, histologically, histomorphometrically, microradiographically, and were also used for tetracycline-labeling studies. TGF-beta 1 did not enhance healing of the bone defect. A combination of growth factors would probably be a more potent osteoinductor than TGF-beta 1 alone.

Animals↗

Intramedullary fixation of cortical bone osteotomies with absorbable self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) rods in rabbits.

Osteotomies of the femoral diaphysis were fixed with absorbable self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) intramedullary rods (4.5 mm x 50-60 mm) in 43 adult rabbits. Follow-up times varied from 3 weeks to 3 yr. After sacrifice histological, oxytetracycline-fluorescence and microradiographic studies of the bones were performed. Strength characteristics and changes in crystallinity and molecular weight of the rods were also measured. All osteotomies were evaluated radiographically. Thirty-six osteotomies (84%) healed uneventfully. The implant disappeared almost totally within 3 yr and histology showed only a minor foreign body reaction. From 6 weeks on, the bending force needed to break the osteotomy was comparable to the bending force needed to break the control bone. The shear strength of the rods displayed only minor changes for the first 24 weeks. Subsequently, the rods rapidly lost their strength and at 48 weeks there was practically no shear strength left, which is ideal for healing of an osteotomy. The present investigation demonstrated, that absorbable. fibrillated SR-PLA96-rods can be used for the intramedullar fixation of simple cortical bone osteotomies in rabbits. These results have encouraged us to continue our studies with the fixation of experimental cortical bone osteotomies in larger species.

Absorbable Implants↗