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Biomedical subjects

A G Mikos

Publications and source records attributed to A G Mikos.

16 recordsLinked to original sources
PubMed1996

Manufacture and characterization of poly(alpha-hydroxy ester) thin films as temporary substrates for retinal pigment epithelium cells.

For many disorders of the retinal pigment epithelium (RPE) for which there are no effective treatments, transplantation of RPE cells may provide a viable means of restoring function. Using a solvent casting technique, we have manufactured thin films of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) 75:25 and 50:50. Non-porous, flexible films with controlled thickness as thin as 12 +/- 3 microns and reproducible surface morphologies and flexural properties were produced. Fetal human RPE cells were found to attach to these substrates when cultured in vitro. The films made using this technique may provide a means of transplanting allogeneic RPE cells as a therapy for a number of ocular diseases related to RPE dysfunction.

Abortion, Therapeutic↗
PubMed1996

Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone.

Bone defects occur in a wide variety of clinical situations, and their reconstruction to provide mechanical integrity to the skeleton is a necessary step in the patient's rehabilitation. The current gold standard for bone reconstruction, the autogenous bone graft, works well in many circumstances. However, autograft reconstruction, along with the available alternatives of allogenous bone graft or poly(methylmethacrylate) bone cement, do not solve all instances of bone deficiency. Novel materials, cellular transplantation and bioactive molecule delivery are being explored alone and in various combinations to address the problem of bone deficiency. The goal of these strategies is to exploit the body's natural ability to repair injured bone with new bone tissue, and to then remodel that new bone in response to the local stresses it experiences. In general, the strategies discussed in this paper attempt to provide the reconstructed region with appropriate initial mechanical properties, encourage new bone to form in the region, and then gradually degrade to allow the new bone to remodel and assume the mechanical support function. Several of the concepts presented below are already finding clinical applications in early patient trials.

Biocompatible Materials↗
PubMed1995

Degradation of polydispersed poly(L-lactic acid) to modulate lactic acid release.

Polydispersed poly(L-lactic acid) (PLLA) membranes comprised of blends of monodispersed PLLA of weight average molecular weight of 82,500 and 7600 were fabricated to investigate the effect of polydispersity on degradation characteristics. The PLLA blends exhibited large spherulites of high molecular weight chains embedded in a low molecular weight matrix. During degradation in phosphate buffer at pH 7.4 and 37 degrees C for 28 d, the release rate of lactic acid increased as the percentage of the low molecular weight component in the blend was increased. For low molecular weight compositions larger than 50%, voids were created in the degrading blends due to the degradation of low molecular weight chains and the concurrent dissolution of lactic acid, and also the release of undegraded particles of high molecular weight. These studies demonstrate the feasibility of modulating lactic acid release during in vivo degradation of PLLA implants by adjusting the polymer polydispersity.

Calorimetry, Differential Scanning↗
PubMed1995

Fabrication of biodegradable polymer scaffolds to engineer trabecular bone.

We present a novel method for manufacturing three-dimensional, biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) foam scaffolds for use in bone regeneration. The technique involves the formation of a composite material consisting of gelatin microspheres surrounded by a PLGA matrix. The gelatin microspheres are leached out leaving an open-cell foam with a pore size and morphology defined by the gelatin microspheres. The foam porosity can be controlled by altering the volume fraction of gelatin used to make the composite material. PLGA 50:50 was used as a model degradable polymer to establish the effect of porosity, pore size, and degradation on foam mechanical properties. The yield strengths and moduli in compression of PLGA 50:50 foams were found to decrease with increasing porosity according to power law relationships. These mechanical properties were however, largely unaffected by pore size. Foams with yield strengths up to 3.2 MPa were manufactured. From in vitro degradation studies we established that for PLGA 50:50 foams the mechanical properties declined in parallel with the decrease in molecular weight. Below a weight average molecular weight of 10,000 the foam had very little mechanical strength (0.02 MPa). These results indicate that PLGA 50:50 foams are not suitable for replacement of trabecular bone. However, the dependence of mechanical properties on porosity, pore size, and degree of degradation which we have determined will aid us in designing a biodegradable scaffold suitable for bone regeneration.

Analysis of Variance↗
PubMed1994

Osteoblast function on synthetic biodegradable polymers.

Rat osteoblasts were cultured on films of biodegradable poly(L-lactic acid) (PLLA), 75:25 poly(DL-lactic-co-glycolic acid) (PLGA), 50:50 PLGA, and poly(glycolic acid) (PGA) for up to 14 days. Osteoblasts attached equally well to all the polymer substrates after 8 h in culture. By day 4 in culture, osteoblasts had exceeded confluency numbers, and their proliferation leveled off by day 7. An increase in alkaline phosphatase (ALP) activity from 1.92 (+/- 0.47) x 10(-7) for day 7 to 5.75 (+/- 0.12) x 10(-7) mumol/cell per min for day 14 was reported for osteoblasts cultured on 75:25 PLGA, which was comparable to that observed for tissue culture polystyrene (TCPS) controls. The ALP activities expressed by osteoblasts cultured on PLLA, 50:50 PLGA, and PGA films did not significantly increase over time. Collagen synthesis for osteoblasts cultured on all polymer substrates was similar to that of TCPS and did not vary with time. The morphology of cultured osteoblasts was not affected by the continuous degradation of the polymer substrates. These results demonstrate that poly(alpha-hydroxy esters) can provide a suitable substrate for osteoblast culture and hold promise in bone regeneration by osteoblast transplantation.

Alkaline Phosphatase↗
PubMed1994

Wetting of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams for tissue culture.

Biodegradable foams of hydrophobic polymers can be efficiently wet by two-step immersion in ethanol and water, which overcomes the hindered entry of water into air-filled pores. Ethanol readily enters into the porous polymer, after which it is diluted and replaced by water. This method was evaluated for porous disks of poly(L-lactic acid) (PLLA) and poly(DL-lactic-co-glycolic acid) (PLGA) foams of copolymer ratios 85:15 and 50:50. For PLLA disks of 0.88 porosity and 1730 microns thickness, prewetting with ethanol for 1 h increased the percentage of void volume filled with water after 48 h from 23 to 79%. The same enhanced entry of water was also observed for prewet PLGA 85:15 disks of 0.86 porosity and 1300 microns thickness, which exhibited an increase from 59 to 97% void volume occupied by water. Furthermore, the water entry even after 1 h was very close to its plateau value for all prewet polymers tested. In recent studies, this method has been useful in uniformly seeding three-dimensional biodegradable polymer substrates for cell and tissue culture.

Culture Techniques↗
PubMed1993

Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers.

Cartilaginous implants for potential use in reconstructive or orthopedic surgery were created using chondrocytes grown on synthetic, biodegradable polymer scaffolds. Chondrocytes isolated from bovine or human articular or costal cartilage were cultured on fibrous polyglycolic acid (PGA) and porous poly(L)lactic acid (PLLA) and used in parallel in vitro and in vivo studies. Samples were taken at timed intervals for assessment of cell number and cartilage matrix (sulfated glycosaminoglycan [S-GAG], collagen). The chondrocytes secreted cartilage matrix to fill the void spaces in the polymer scaffolds that were simultaneously biodegrading. In vitro, chondrocytes grown on PGA for 6 weeks reached a cell density of 5.2 x 10(7) cells/g, which was 8.3-fold higher than at day 1, and equalled the cellularity of normal bovine articular cartilage. In vitro, the cell growth rate was approximately twice as high on PGA as it was on PLLA; cells grown on PGA produced S-GAG at a high steady rate, while cells grown on PLLA produced only minimal amounts of S-GAG. These differences could be attributed to polymer geometry and biodegradation rate. In vivo, chondrocytes grown on both PGA and PLLA for 1-6 months maintained the three-dimensional (3-D) shapes of the original polymer scaffolds, appeared glistening white macroscopically, contained S-GAG and type II collagen, and closely resembled cartilage histologically. These studies demonstrate the feasibility of culturing isolated chondrocytes on biodegradable polymer scaffolds to regenerate 3-D neocartilage.

Animals↗
PubMed1993

Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation.

A novel method was developed to prepare three-dimensional structures with desired shapes used as templates for cell transplantation. The produced biomaterials are highly porous with large surface/volume and provide the necessary space for attachment and proliferation of the transplanted cells. The processing technique calls for the formation of a composite material with nonbonded fibers embedded in a matrix followed by thermal treatment and the selective dissolution of the matrix. To evaluate the technique, poly(glycolic acid) (PGA) fiber meshes were bonded using poly(L-lactic acid) (PLLA) as a matrix. The bonded structures were highly porous with values of porosity up to 0.81 and area/volume ratios as high as 0.05 micron-1.

Animals↗
PubMed1993

Laminated three-dimensional biodegradable foams for use in tissue engineering.

A novel processing technique is reported to construct three-dimensional biodegradable polymer foams with precise anatomical shapes. The technique involved the lamination of highly-porous membranes of porosities up to 90%. Implants with specific shapes were prepared made of poly(L-lactic acid) and copolymers of poly(DL-lactic-co-glycolic acid) to evaluate feasibility. The biomaterials produced have pore morphologies similar to those of the constituent membranes. The pores of adjacent layers of laminated devices are interconnected, resulting in continuous pore structures. The compressive creep behaviour of multilayered devices is also similar to that of the individual layers. Recent discoveries from our group and others that organs and tissues can be regenerated and reconstructed, using cells cultured on synthetic biodegradable polymers, renders this method useful in creating polymer-cell graft for use in cell transplantation.

Biocompatible Materials↗
PubMed1993

Cell seeding in porous transplantation devices.

Porous laminated discs of 1.35 cm diameter and thickness of 0.5 cm fashioned from biodegradable polymers were used as scaffolds for the transplantation of isolated cell populations. The distribution of cells seeded in these devices via injection was modelled with a system of dyed polymeric microparticles. Optimization of parameters related to device design and surgical injection conditions was carried out to maximize the device volume effectively employed in cell transplantation. The area of distribution on the top surface of each device was determined by image analysis techniques and used as a measure of the spatial distribution of injected particles. For poly(L-lactic acid) devices of porosity of 0.83 and median pore diameter of 166 microns seeded with 6 microns beads under standard injection conditions, the average surface area of distribution was 44.45% (+/- 3.36%). The device pore size was found to be a crucial determinant of particle distribution, whilst particle size in the range of 1-10 microns was not found to be important for the devices tested. Application of these results to the seeding of hepatocyte suspensions was made.

Animals↗
PubMed1988

Flory interaction parameter chi for hydrophilic copolymers with water.

In biomedical applications of hydrophilic polymers knowledge is required of the thermodynamic interactions between the candidate biomaterial and biological fluids. Since information on these interactions is not readily available, a new method is proposed here to estimate the copolymer-water Flory interaction parameter, chi, for biomaterials. The method is based on the pairwise thermodynamic interactions of copolymer segments and solvent molecules. It is validated using data for an important biomedical hydrogel, poly(2-hydroxyethyl methacrylate-co-methacrylic acid), in contact with water.

Biocompatible Materials↗
PubMed1987

Prediction of feed comonomer and solvent composition for monomer-free polymer production.

A method has been developed to establish the desirable polymerization conditions for the production of monomer-free polymer at 100% conversion. The limits of desirable comonomer composition and solvent content in the feed are determined for both bulk and solution homo- and copolymerizations. An example of the result of the polymerization of 2-hydroxyethyl methacrylate and methyl methacrylate is used to illustrate the application of this method.

Mathematics↗
PubMedDate not supplied

Pore morphology effects on the fibrovascular tissue growth in porous polymer substrates.

The feasibility of developing biodegradable polymer scaffolds to engineer tissues was investigated by studying the effects of pore size on the dynamics of fibrovascular tissue ingrowth. Tissue advanced into amorphous poly(L-lactic acid) porous substrates faster as the pore diameter increased. Porous cylindrical devices of 13.5 mm diameter, 5 mm thickness, and approximately 500 microns pore size were filled completely by tissue 5 days postimplantation. Although prevascularized devices possessed minimal void volume for cell seeding to regenerate metabolic organs, they hold promise in the regeneration of tubular tissues by relying on the epithelization of prevascularized grafts.

Alginates↗
PubMedDate not supplied

Dynamics of fibrovascular tissue ingrowth in hydrogel foams.

We have investigated and quantified the degree of fibrovascular tissue ingrowth in cylindrical poly(vinyl alcohol) (PVA) foams of 12.5 mm diameter, 5 mm thickness, and 71% porosity implanted in the mesentery of rats over a period of 25 days. Fibrovascular tissue penetrated the center of PVA foams 5 days postimplantation yet the void fraction available for cell seeding was 55% and the volume average pore diameter was 190 (+/- 39) microns. By 10 days postimplantation the void fraction had decreased to 32% and the volume average pore diameter was 121 (+/- 20) microns. As time elapsed fibrovascular tissue continued to expand and fill the remaining pore space. At 15 days postimplantation the void space was impractical for cell seeding and continued to decrease through the remainder of the study. Our data suggest that hydrogel foams with a polydispersed pore morphology can be prevascularized with adequate space for cell seeding as the volume of tissue penetrating the foam is limited by the smaller pores in the foam structure; however, available void space for cell seeding decreases with time.

Animals↗
PubMedDate not supplied

Fabrication of pliable biodegradable polymer foams to engineer soft tissues.

We have fabricated pliable, porous, biodegradable scaffolds with poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) blends using a solvent-casting and particulate-leaching technique. Our study investigated the effects of four different processing parameters on pliability and pore morphology of the biodegradable scaffolds. The parameters investigated were the PLGA copolymer ratio, the PLGA/PEG blend ratio, the initial salt weight fraction, and the salt particle size. A wide range of shear moduli (0.59 to 9.55 MPa), porosities (0.798 to 0.942), and median pore diameters (71 to 154 microns) was able to be achieved by varying the combination of these parameters. Our study indicates that initial salt weight fraction and PLGA/PEG blend ratio have the most significant effects on the physico-mechanical properties of the scaffolds. Enhanced pliability of the three dimensional foams made with blends of PLGA and PEG is evidenced by the ability to roll them into a tube without macroscopic damage to the scaffold. Pliable polymer substrates hold great promise for regeneration of soft tissues such as skin, or those requiring a tubular conformation such as intestine or vascular grafts.

Biodegradation, Environmental↗