Paul H.M. Spauwen

On the nature of hypertrophic scars and keloids: A review

On the Nature of Hypertrophic Scars and Keloids: A Review Frank Niessen;Paul Spauwen;Joost Schalkwijk;Moshe Kon; Plastic and Reconstructive Surgery

rhBMP-2 release from injectable poly(DL-lactic-co-glycolic acid)/calcium-phosphate cement composites.

Background: In bone tissue engineering, poly(DL-lactic-co-glycolic acid) (PLGA) microparticles are frequently used as a delivery vehicle for bioactive molecules. Calcium phosphate cement is an injectable, osteoconductive, and degradable bone cement that sets in situ. The objective of this study was to create an injectable composite based on calcium phosphate cement embedded with PLGA microparticles for sustained delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2).Methods: 125 I-labeled rhBMP-2 was incorporated in PLGA microparticles. PLGA microparticle/calcium-phosphate cement composites were prepared in a ratio of 30:70 by weight. Material properties were evaluated by scanning electron microscopy, microcomputed tomography, and mechanical testing. Release kinetics of rhBMP-2 from PLGA/calcium-phosphate cement disks and PLGA microparticles alone were determined in vitro in two buffer solutions (pH 7.4 and pH 4.0) for up to twenty-eight days.Results: The entrapment yield of rhBMP-2 in PLGA microparticles was a mean (and standard deviation) of 79% ± 8%. Analysis showed spherical PLGA microparticles (average size, 17.2 ±1.3 &mgr;m) distributed homogeneously throughout the nanoporous disks. The average compressive strength was significantly lower (p < 0.001) for PLGA and calcium-phosphate cement composite scaffolds than for calcium-phosphate cement scaffolds alone (6.4 ± 0.6 MPa compared with 38.6 ± 2.6 MPa, respectively). Average rhBMP-2 loading was 5.0 ± 0.4 &mgr;g per 75-mm 3 disk. Release of rhBMP-2 was limited for all formulations. At pH 7.4, 3.1% ± 0.1% of the rhBMP-2 was released from the PLGA/calcium-phosphate cement disks and 18.0% ± 1.9% was released from the PLGA microparticles alone after twenty-eight days. At pH 4.0, PLGA/calcium-phosphate cement disks revealed more release of rhBMP-2 than did PLGA microparticles alone (14.5% ± 6.3% compared with 5.4% ± 0.7%) by day 28.Conclusions: These results indicate that preparation of a PLGA/calcium-phosphate cement composite for the delivery of rhBMP-2 is feasible and that the release of rhBMP-2 is dependent on the composite composition and nanostructure as well as the pH of the release medium.Clinical Relevance: An osteoconductive and osteoinductive rhBMP-2-loaded PLGA/calcium-phosphate cement composite may potentially result in an injectable bone-graft substitute for the regeneration of bone in ectopic or orthotopic sites.

Nonsyndromic orofacial clefts: association with maternal hyperhomocysteinemia

Maternal folic acid supplementation has been suggested to play a role in the prevention of nonsyndromic orofacial clefts, i.e., cleft lip +/- cleft palate. Using a case-control design, we investigated vitamin-dependent homocysteine metabolism in 35 mothers with nonsyndromic orofacial cleft offspring and 56 control mothers with nonmalformed offspring. A standardized oral methionine loading test was performed, in which fasting and afterload plasma total homocysteine, serum and red-cell folate, serum vitamin B12, and whole-blood vitamin B6 levels were determined. We found that both fasting (P < 0.01) as well as afterload (P < 0.05) homocysteine concentrations were significantly higher in cases compared to controls. Hyperhomocysteinemia, defined by a fasting and/or afterload homocysteine concentration above the 97.5th percentile, was present in 15.6% of the cases and in 3.6% of controls (odds ratio, 5.3 (1.1-24.2)). The median concentrations of serum (P < 0. 01) and red-cell (P < 0.05) folate were significantly higher, and vitamin B6 concentrations appeared to be significantly lower (P < 0. 05), in cases compared with controls. No significant difference was observed between groups for vitamin B12. These preliminary data offer evidence that maternal hyperhomocysteinemia may be a risk factor for having nonsyndromic orofacial cleft offspring.

Bone tissue reconstruction using titanium fiber mesh combined with rat bone marrow stromal cells

The study aim was to evaluate the effect of bone marrow stromal cells (BMSCs) cultured in titanium fiber mesh and implanted in a rat cranial defect. A total of 24 titanium meshes were placed in a tube containing 10 ml BMSC suspension (3 x 10(6)cells/ml) and the tube was rotated on a rotation plate (2 rpm) during 3 h. Thereafter, meshes with cells were subcultured for 1 day under standard conditions. Cell-loaded implants and non-cell-loaded controls were placed in a 8 mm cranial defect and retrieved after 3, 15 and 30 days of implantation. Histology showed that after 3 days of implantation, the mesh porosity of both implant groups was mainly invaded with blood cells. On the other hand, at 15 days of implantation, the cell-loaded implants were filled for 15 +/- 10% of their volume with bone, while the controls showed 1.5 +/- 3.5% of bone. The 30-day cell-loaded implants showed 40 +/- 12.5% of bone and the 30-day control implants 17 +/- 14.5%. At both implantation times the differences were statistically significant. Therefore, we conclude that inoculation of titanium fiber mesh with BMSCs can improve the bone healing capacity of this material.

Bone formation in calcium-phosphate-coated titanium mesh

The osteogenic activity of porous titanium fiber mesh and calcium phosphate (Ca-P)-coated titanium fiber mesh loaded with cultured syngeneic osteogenic cells was compared in a syngeneic rat ectopic assay model. In 30 syngeneic rats, (Ca-P)-coated and non-coated porous titanium implants were subcutaneously placed either without or loaded with cultured rat bone marrow (RBM) cells. Fluorochrome bone markers were injected at 2, 4, and 6 weeks. The rats were sacrificed, and the implants were retrieved at 2, 4, and 8 weeks post-operatively. Histological analysis demonstrated that none of the (Ca-P)-coated and non-coated meshes alone supported bone formation at any time period. In RBM-loaded implants, bone formation started at 2 weeks. At 4 weeks, bone formation increased. However, at 8 weeks bone formation was absent in the non-coated titanium implants, while it had remained in the (Ca-P)-coated titanium implants. Also, in (Ca-P)-coated implants more bone was formed than in non-coated samples. In general, osteogenesis was characterized by the occurrence of multiple spheres in the porosity of the mesh. The accumulation sequence of the fluorochrome markers showed that the newly formed bone was deposited in a centrifugal manner starting at the center of a pore. Our results show that the combination of Ti-mesh with RBM cells can indeed generate bone formation. Further, our results confirm that a thin Ca-P coating can have a beneficial effect on the bone-generating properties of a scaffold material.

A Review of Surgical Informed Consent: Past, Present, and Future. A Quest to Help Patients Make Better Decisions

BackgroundInformed consent (IC) is a process requiring a competent doctor, adequate transfer of information, and consent of the patient. It is not just a signature on a piece of paper. Current consent processes in surgery are probably outdated and may require major changes to adjust them to modern day legislation. A literature search may provide an opportunity for enhancing the quality of the surgical IC (SIC) process.MethodsRelevant English literature obtained from PubMed, Picarta, PsycINFO, and Google between 1993 and 2009 was reviewed.ResultsThe body of literature with respect to SIC is slim and of moderate quality. The SIC process is an underestimated part of surgery and neither surgeons nor patients sufficiently realize its importance. Surgeons are not specifically trained and lack the competence to guide patients through a legally correct SIC process. Computerized programs can support the SIC process significantly but are rarely used for this purpose.ConclusionsIC should be integrated into our surgical practice. Unfortunately, a big gap exists between the theoretical/legal best practice and the daily practice of IC. An optimally informed patient will have more realistic expectations regarding a surgical procedure and its associated risks. Well-informed patients will be more satisfied and file fewer legal claims. The use of interactive computer-based programs provides opportunities to improve the SIC process.

Evaluation of Various Seeding Techniques for Culturing Osteogenic Cells on Titanium Fiber Mesh

The objective of the present study was to learn more about the effect of seeding and loading techniques on the osteogenic differentiation in vitro of rat bone marrow cells into titanium fiber mesh. This material was used as received or subjected to glow discharge treatment (RFGD). The seeding methods that were used included a so-called droplet, cell suspension (high and low cell density), and rotating plate method. Osteogenic cells were cultured for 4, 8, and 16 days into titanium fiber mesh. DNA, osteocalcin, scanning electron microscopy (SEM) analysis, and calcium measurements were used to determine cellular proliferation and differentiation. DNA analysis of the differently seeded specimens showed that proliferation proceeded faster in the first versus second run for droplet and cell suspension samples. No clear and distinct additional effect was found when RFGD treatment was used. Statistical analyses revealed that high cell density and low rotational speed resulted always in a significantly higher DNA content. Calcium measurements and osteocalcin analysis showed that using high cell densities during inoculation of the scaffolds prevented the occurrence of differences between experimental runs. SEM examination showed that for droplet and cell suspension samples cells were present at only one side of the mesh. The mesh side where the cell sheet was observed depended on the additional use of glow discharge treatment. On these materials, the cells had penetrated through the meshes and formed a cell sheet at the bottom side. When rotation was used, no cell sheet was formed and cells had invaded the meshes and were growing around the titanium fibers. On the basis of our results, we conclude that (1). titanium fiber mesh is indeed suitable to support the osteogenic expression of bone marrow cells, and (2). changing the initial cell density as well as the use of dynamic seeding methods can influence the osteogenic capacity of the scaffold.

The kinetic and biological activity of different loaded rhBMP-2 calcium phosphate cement implants in rats

The healing of large bone defects can be improved by osteogenic bone graft substitutes, due to growth factor inclusion. A sustained release of these growth factors provides more efficient bioactivity when compared with burst release and might reduce the dose required for bone regeneration, which is desirable for socioeconomical and safety reasons. In this study, we compared different rhBMP-2 loadings in a sustained release system of CaP cement and PLGA-microparticles and were able to couple kinetic to biological activity data. Fifty-two rats received a critical-size cranial defect, which was left open or filled with the cement composites. The implants consisted of plain, high, and five-fold lower dose rhBMP-2 groups. Implantation time was 4 and 12 weeks. Longitudinal in vivo release was monitored by scintigraphic imaging of (131)I-labeled rhBMP-2. Quantitative analysis of the scintigraphic images revealed a sustained release of (131)I-rhBMP-2 for both doses, with different release profiles between the two loadings. However, around 70% of the initial dose was retained in both implant formulations. Although low amounts of rhBMP-2 were released (2.4 +/- 0.8 mug in 5 weeks), histology showed defect bridging in the high-dose implants. Release out of the low-dose implants was not sufficient to enhance bone formation. Implant degradation was limited in all formulations, but was mainly seen in the high-dose group. Low amounts of sustained released rhBMP-2 were sufficient to bridge critically sized defects. A substantial amount of rhBMP-2 was retained in the implants because of the slow release rate and the limited degradation.

Donor-Site Complications in Vascularized Bone Flap Surgery

Microvascular osteocutaneous free flaps have given reconstructive surgeons a powerful tool in the reconstruction of composite defects in head and neck surgery. Radial forearm, scapula, iliac crest, and fibula flaps have been used extensively in mandibular reconstruction. The inevitable donor-site morbidity of these osteocutaneous flaps has received less attention than the reconstructive advantages. We have reviewed the literature for each type of flap to determine the kind, incidence, and consequences of flap associated morbidity. In the future, tissue-engineered prefabricated free flaps might play an important role.

Untreated Hemangiomas : Growth Pattern and Residual Lesions

Background: Hemangiomas of infancy can give rise to alarm because of their rapid growth and occasional dramatic appearance. The objective of this study was to investigate the growth pattern of hemangiomas and risk factors for residual lesions. Methods: A follow-up study was performed of patients with hemangiomas that were clinically monitored between 1985 and 2000 and who did not receive any treatment. The data were retrieved from medical files. Patients (parents) were asked to complete a questionnaire and invited to our outpatient clinic where the questionnaire was discussed and physical examination was performed. The growth phases of the hemangioma were documented, the timeline of these phases was constructed, and an assessment was made of the residual lesion if present. Results: In 97 patients, 137 hemangiomas were evaluated. A precursor lesion was present in 48 percent of children. Maximum size was reached in 8 months. Involution started at a median age of 2 years and was completed at a median age of 4 years. Residual lesions were present in 69 percent of cases. Superficial nodular hemangiomas showed significantly more residual lesions (74 percent) than the deep hemangiomas (25 percent) (p < 0.001; odds ratio, 8.4; 95 percent confidence interval, 2.4 to 29.1). Untreated infection, ulceration, or bleeding produced a scar in 97 percent of the cases. Conclusions: Epidermal invasion of the hemangioma is of predictive value for residual lesions. There is no correlation between the growth pattern of a hemangioma and the risk for a residual lesion. This may add to a more detailed prediction of outcome and may help to decide which patient should be treated or not.