Biomedical subjects

Michael T Longaker

Publications and source records attributed to Michael T Longaker.

At least 37 records · Page 2Linked to original sources

PubMed2006

Wnt-4 expression is increased in fibroblasts after TGF-beta1 stimulation and during fetal and postnatal wound repair.

BACKGROUND: Wnt-4 is a mitogen expressed during postnatal repair and scar formation; however, its expression profile during scarless repair is unknown. Transforming growth factor (TGF)-beta1 has high expression during healing with scar formation. Whether TGF-beta1 directly influences Wnt-4 expression in fetal or postnatal fibroblasts has not been examined. METHODS: Primary fetal and postnatal mouse fibroblasts were stimulated with TGF-beta1 and Wnt-4 expression quantitated by real-time polymerase chain reaction. Fetal E17 and postnatal mouse excisional wounds were also analyzed for Wnt-4 expression by real-time polymerase chain reaction. RESULTS: In E17 fibroblasts after TGF-beta1 stimulation, Wnt-4 expression increased 4-fold at 1 hour (p < 0.05) and peaked with an 11-fold increase at 2 hours (p < 0.05). By 24 hours, expression decreased to 2-fold baseline levels (p < 0.05). In postnatal fibroblasts, Wnt-4 expression also increased after TGF-beta stimulation, but peak expression was larger and relatively delayed, with a 17-fold increase at 12 hours (p < 0.005). Expression levels at 24 hours were still 4-fold greater than baseline (p < 0.05). In E17 fetal skin, Wnt-4 expression was 3.5-fold greater compared with 3-week-old mice (p < 0.005). Small increases in Wnt-4 expression (less than 2-fold) occurred during both fetal scarless and postnatal scarring mouse wound repair. CONCLUSION: The authors' data suggest that TGF-beta directly increases Wnt-4 expression in fetal and postnatal fibroblasts and that Wnt-4 is increased in both fetal and postnatal repair.

Animals↗

PubMed2006

An in vivo mouse excisional wound model of scarless healing.

BACKGROUND: The purpose of this study was to develop a reproducible murine model of fetal scarless wound healing. METHODS: One-millimeter excisional wounds were made in fetal skin at gestational days 16.5 (E17) and 18.5 (E19) (term = day 21.5, or E22) and marked with India ink. Fetal mortality was less than 30 percent in E17 fetuses and 0 percent in E19 fetuses. Control postnatal 2-mm open wounds were made in 3-week-old mice. RESULTS: At 48 hours, E17 skin wounds had healed completely. E19 skin wounds also healed but were marked by skin irregularity at the wound site. Histologically, E17 wounds had fine reticular collagen architecture by trichrome staining and hair follicle regeneration. In contrast, E19 wounds healed with collagen deposition and scar formation and no hair follicle regeneration. CONCLUSIONS: The authors have developed a reliable mouse model of fetal scarless repair to help elucidate the mechanism of scarless wound healing to take advantage of genetically modified animals. The knowledge gained may be used to manipulate scarring in the adult to produce a more fetal-like wound.

Animals↗

PubMed2006

Early-gestation fetal scarless wounds have less lysyl oxidase expression.

BACKGROUND: Lysyl oxidase cross-links collagen and elastin. Because cross-linking likely influences collagen architecture, the authors compared lysyl oxidase expression during scarless and scarring fetal dermal wound repair. METHODS: Excisional dermal wounds were made on E17 (gestational day 16.5) and E19 (gestational day 18.5) mouse fetuses. Skin and wound RNA was collected at 8, 12, and 24 hours. Quantitative real-time polymerase chain reaction was performed for lysyl oxidase. The effect of transforming growth factor (TGF)-beta1 on lysyl oxidase expression in fetal fibroblasts was tested. Confluent primary fetal and postnatal fibroblast cultures were stimulated with TGF-beta1 for 24 hours, and lysyl oxidase expression was quantitated by performing real-time polymerase chain reaction. Lysyl oxidase expression was also quantitated in unwounded fetal skin to determine its expression profile during development. RESULTS: E17 and E19 fetal skin had approximately 2-fold greater lysyl oxidase expression than postnatal skin (p < 0.01), and fetal fibroblasts had greater baseline lysyl oxidase expression than postnatal fibroblasts. After TGF-beta1 stimulation, fetal and postnatal fibroblasts responded with increases in lysyl oxidase expression. In E17 early-gestation scarless fetal wounds, lysyl oxidase had small increases (<1.5-fold) in expression from 1 to 12 hours. In late-gestation E19 scarring fetal wounds, lysyl oxidase increased 1.8-fold at 8 hours and 2-fold at 12 hours, which was significantly greater than the changes observed in E17 scarless wounds (p < 0.01 for each). CONCLUSIONS: Lysyl oxidase has greater expression in E19 late-gestation wounds that heal with scar compared with E17 early-gestation scarless wounds. This suggests a role for lysyl oxidase in scar formation.

Animals↗

PubMed2006

Fetal and adult fibroblasts have similar TGF-beta-mediated, Smad-dependent signaling pathways.

BACKGROUND: The scarless fetal skin-healing mechanism is mediated in part by the fibroblast and involves differential expression of transforming growth factor (TGF)-beta isoforms 1 and 3. The authors hypothesized that fetal and adult fibroblasts respond differently to TGF-beta isoform-specific stimulation, which may influence whether wounds scar. Connective tissue growth factor (CTGF), Smad3, and Smad7 are TGF-beta target genes. Expression of these targets was quantitated after TGF-beta1 and -beta3 stimulation of fetal and adult fibroblasts. METHODS: Primary mouse fibroblast cultures at gestational day 16.5 (E17), 18.5 (E19), and 6 weeks (adult) were stimulated with TGF-beta1 or TGF-beta3. Quantitative polymerase chain reaction was performed for CTGF, Smad3, and Smad7 expression. RESULTS: CTGF was reduced four-fold in E17 and E19 compared with adult fibroblasts (p < 0.005). After TGF-beta1 stimulation, CTGF expression increased more than 60-fold in both E17 and E19 (p < 0.01), which was three-fold greater than that in adult fibroblasts (p < 0.005). TGF-beta3 induced more than 70-fold, 50-fold, and 20-fold increases in CTGF expression in E17, E19, and adult fibroblasts, respectively (p < 0.01 for each). Both TGF-beta1 and -beta3 decreased Smad3 expression and increased Smad7 expression in each fibroblast type, suggesting that intact TGF-beta-mediated signaling pathways were present. CONCLUSIONS: Fetal (E17 and E19) fibroblasts have lower CTGF expression compared with adult fibroblasts. However, fetal fibroblasts have larger increases in CTGF expression after TGF-beta1 or -beta3 stimulation. Fetal and adult mouse fibroblasts have similar TGF-beta1 and TGF-beta3 transcriptional regulation of Smad3 and Smad7. This suggests that scarless healing is likely not mediated by different Smad-dependent transcriptional responses to TGF-beta isoforms in the fetal E17 fibroblast.

Age Factors↗

PubMed2006

Innovation in surgery: a historical perspective.

OBJECTIVE: To describe the field of surgical innovation from a historical perspective, applying new findings from research in technology innovation. BACKGROUND: While surgical innovation has a rich tradition, as a field of study it is embryonic. Only a handful of academic centers of surgical innovation exist, all of which have arisen within the last 5 years. To this point, the field has not been well defined, nor have future options to promote surgical innovation been thoroughly explored. It is clear that surgical innovation is fundamental to surgical progress and has significant health policy implications. A process of systematically evaluating and promoting innovation in surgery may be critical in the evolving practice of medicine. METHODS: A review of the academic literature in technology innovation was undertaken. Articles and books were identified through technical, medical, and business sources. Luminaries in surgical innovation were interviewed to develop further relevance to surgical history. The concepts in technology innovation were then applied to innovation in surgery, using the historical example of surgical endoscopy as a representative area, which encompasses millennia of learning and spans multiple specialties of care. RESULTS: The history of surgery is comprised largely of individual, widely respected surgeon innovators. While respecting individual accomplishments, surgeons as a group have at times hindered critical innovation to the detriment of our profession and patients. As a clinical discipline, surgery relies on a tradition of research and attracting the brightest young minds. Innovation in surgery to date has been impressive, but inconsistently supported. CONCLUSION: A body of knowledge on technology innovation has been developed over the last decade but has largely not been applied to surgery. New surgical innovation centers are working to define the field and identify critical aspects of surgical innovation promotion. It is our responsibility as a profession to work to understand innovation in surgery, discover, translate, and commercialize advances to address major clinical problems, and to support the future of our profession consistently and rationally.

General Surgery↗

PubMed2006

P38 MAP kinase mediates transforming growth factor-beta2 transcription in human keloid fibroblasts.

Keloids are abnormal fibrous growths of the dermis that develop only in response to wounding and represent a form of benign skin tumor. Previous studies have shown increased protein levels of TGF-beta in keloid tissue, suggesting a strong association with keloid formation leading us to examine mechanisms for why it is more highly expressed in keloids. Here, we use serum stimulation as an in vitro model to mimic a component of the wound microenvironment and examine differential gene expression in keloid human fibroblasts (KFs) vs. normal human fibroblasts (NFs). Transcription of TGF-beta2 was rapid and peaked between 1 and 6 h after serum stimulation in KFs vs. NFs. We confirmed increased TGF-beta activity in the conditioned medium from KFs, but not NFs. Inhibition of second messenger signaling pathways demonstrated that only the p38 MAPK inhibitor SB-203580 could block upregulation of TGF-beta2 following serum stimulation in KFs. Immunoblotting demonstrated that p38 MAPK was phosphorylated within 15 min and was maintained at a high level in KFs but not in NFs. The transcription factors activating transcription factor-2 and Elk-1 are activated by p38 MAPK, and also showed rapid and prolonged phosphorylation kinetics in KFs but not in NFs. In conclusion, increased TGF-beta2 transcription in response to serum stimulation in KFs appears to be mediated by the p38 MAPK pathway. This suggests the mechanism of keloid pathogenesis may be due in part to an inherent difference in how the fibroblasts respond to wounding.

Cells, Cultured↗

PubMed2006

Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers.

BACKGROUND: Inadequate oxygen (hypoxia) triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer.

Adult↗

PubMed2006

Mannose-6-phosphate, an inhibitor of transforming growth factor-beta, improves range of motion after flexor tendon repair.

BACKGROUND: Adhesion formation between the flexor tendon and its surrounding fibro-osseous sheath results in a decreased postoperative range of motion in the hand. Transforming growth factor-beta (TGF-beta) is a key cytokine in the pathogenesis of tissue fibrosis. In this study, the effects of two natural inhibitors of TGF-beta, decorin and mannose-6-phosphate, were investigated in vitro and in vivo. METHODS: In the in vitro investigation, primary cell cultures from rabbit flexor tendon sheath, epitenon, and endotenon were established and each was supplemented with TGF-beta along with increasing doses of decorin or mannose-6-phosphate. Collagen-I production was measured with enzyme-linked immunosorbent assay (ELISA). For the in vivo study, rabbit zone-II flexor tendons were transected and then immediately repaired. Single intraoperative graded doses of decorin, mannose-6-phosphate, or phosphate-buffered saline solution (control) were added to the repair sites, and the forepaws were tested for the range of motion and repair strength at eight weeks postoperatively. RESULTS: Decorin and mannose-6-phosphate both reduced TGF-beta upregulated collagen production. Intraoperative application of low-dose mannose-6-phosphate significantly improved the range of motion of the operatively treated digits. The effect on breaking strength of the tendon repair was inconclusive. CONCLUSIONS: Mannose-6-phosphate is effective in reducing TGF-beta upregulated collagen production in an in vitro model. This finding correlated with our in vivo finding that a single intraoperative dose of mannose-6-phosphate improved the postoperative range of motion.

Animals↗

PubMed2005

Relationships between tissue dilatation and differentiation in distraction osteogenesis.

Mechanical factors modulate the morphogenesis and regeneration of mesenchymally derived tissues via processes mediated by the extracellular matrix (ECM). In distraction osteogenesis, large volumes of new bone are created through discrete applications of tensile displacement across an osteotomy gap. Although many studies have characterized the matrix, cellular and molecular biology of distraction osteogenesis, little is known about relationships between these biological phenomena and the local physical cues generated by distraction. Accordingly, the goal of this study was to characterize the local physical environment created within the osteotomy gap during long bone distraction osteogenesis. Using a computational approach, we quantified spatial and temporal profiles of three previously identified mechanical stimuli for tissue differentiation-pressure, tensile strain and fluid flow-as well as another candidate stimulus-tissue dilatation (volumetric strain). Whereas pressure and fluid velocity throughout the regenerate decayed to less than 31% of initial values within 20 min following distraction, tissue dilatation increased with time, reaching steady state values as high as 43% strain. This dilatation created large reductions and large gradients in cell and ECM densities. When combined with previous findings regarding the effects of strain and of cell and ECM densities on cell migration, proliferation and differentiation, these results indicate two mechanisms by which tissue dilatation may be a key stimulus for bone regeneration: (1) stretching of cells and (2) altering cell and ECM densities. These results are used to suggest experiments that can provide a more mechanistic understanding of the role of tissue dilatation in bone regeneration.

Animals↗

PubMed2005

Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells.

Recent studies have demonstrated that adipose-derived mesenchymal cells (AMCs) offer great promise for cell-based therapies because of their ability to differentiate toward bone, cartilage, and fat. Given that cartilage is an avascular tissue and that mesenchymal cells experience hypoxia during prechondrogenic condensation in endochondral ossification, the goal of this study was to understand the influence of oxygen tension on AMC differentiation into bone and cartilage. In vitro chondrogenesis was induced using a three-dimensional micromass culture model supplemented with TGF-beta1. Collagen II production and extracellular matrix proteoglycans were assessed with immunohistochemistry and Alcian blue staining, respectively. Strikingly, micromasses differentiated in reduced oxygen tension (2% O(2)) showed markedly decreased chondrogenesis. Osteogenesis was induced using osteogenic medium supplemented with retinoic acid or vitamin D and was assessed with alkaline phosphatase activity and mineralization. AMCs differentiated in both 21 and 2% O(2) environments. However, osteogenesis was severely diminished in a low-oxygen environment. These data demonstrated that hypoxia strongly inhibits in vitro chondrogenesis and osteogenesis in AMCs.

Adipose Tissue↗

PubMed2005

Gene profiling of cells expressing different FGF-2 forms.

Fibroblast Growth Factor-2 (FGF-2) induces cell proliferation, cell migration, embryonic development, cell differentiation, angiogenesis and malignant transformation. The four forms of FGF-2 (Low Molecular Weight) and (High Molecular Weights) are alternative translation products, and have a different subcellular localization: the high molecular weight (HMWFGF-2) forms are nuclear while the low molecular weight form, (LMWFGF-2) is mainly cytoplasmic. Our previous work demonstrated NIH 3T3 cells expressing different FGF-2 forms, displayed a different phenotype, suggesting that nuclear and cytoplasmic forms of FGF-2 may have different functions. Here we report a cDNA microarray-based study in NIH 3T3 fibroblasts expressing different FGF-2 forms. Several candidate genes that affect cell-cycle, tumor suppression, adhesion and transcription were identified as possible mediators of the HMWFGF-2 phenotype and signaling pattern. These results demonstrated that HMWFGF-2 and LMWFGF-2 target the expression of different genes. Particularly, our data suggest that HMWFGF-2 forms may function as inducers of growth inhibition and tumor suppression activities.

Animals↗

PubMed2005

Age-dependent residual tensile strains are present in the dura mater of rats.

The objectives of this study were to determine whether residual tensile strains exist in the dura mater of mammals in vivo, and whether the strains are age-dependent. We made incisions in the parietal dura mater of immature and mature rats, and measured the retraction of the dura mater from each incision. We then used a finite-element model to calculate the strain present in the parietal dura mater of each rat. We found that age-dependent residual tensile strains are present in the dura mater of rats. The mean average residual strain of the immature rats was significantly larger than that of the mature rats (4.96+/-1.54% (s.d.) versus 0.39+/-0.13%, p<0.0001), with the mean strain calculated in the mature rats of the order of the minimum measurement that could be made using our experimental approach. In addition, in the immature rats mean residual strain in the longitudinal direction was significantly larger than mean residual strain in the transverse direction (6.11+/-3.62% versus 3.82+/-2.64%, p=0.0218). Our findings show that age-dependent residual tensile strains exist in the dura mater of rats. We speculate that these strains may reflect the rate and direction of cranial growth and may also influence cranial healing.

Aging↗

PubMed2005

Sox9 neural crest determinant gene controls patterning and closure of the posterior frontal cranial suture.

Cranial suture development involves a complex interaction of genes and tissues derived from neural crest cells (NCC) and paraxial mesoderm. In mice, the posterior frontal (PF) suture closes during the first month of life while other sutures remain patent throughout the life of the animal. Given the unique NCC origin of PF suture complex (analogous to metopic suture in humans), we performed quantitative real-time PCR and immunohistochemistry to study the expression pattern of the NCC determinant gene Sox9 and select markers of extracellular matrix. Our results indicated a unique up-regulated expression of Sox9, a regulator of chondrogenesis, during initiation of PF suture closure, along with the expression of specific cartilage markers (Type II Collagen and Type X Collagen), as well as cartilage tissue formation in the PF suture. This process was followed by expression of bone markers (Type I Collagen and Osteocalcin), suggesting endochondral ossification. Moreover, we studied the effect of haploinsufficiency of the NCC determinant gene Sox9 in the NCC derived PF suture complex. A decrease in dosage of Sox9 by haploinsufficiency in NCC-derived tissues resulted in delayed PF suture closure. These results demonstrate a unique development of the PF suture complex and the role of Sox9 as an important contributor to timely and proper closure of the PF suture through endochondral ossification.

Animals↗

PubMed2005

Angiogenesis is required for successful bone induction during distraction osteogenesis.

UNLABELLED: The role of angiogenesis during mechanically induced bone formation is incompletely understood. The relationship between the mechanical environment, angiogenesis, and bone formation was determined in a rat distraction osteogenesis model. Disruption of either the mechanical environment or endothelial cell proliferation blocked angiogenesis and bone formation. This study further defines the role of the mechanical environment and angiogenesis during distraction osteogenesis. INTRODUCTION: Whereas successful fracture repair requires a coordinated and complex transcriptional program that integrates mechanotransductive signaling, angiogenesis, and osteogenesis, the interdependence of these processes is not fully understood. In this study, we use a system of bony regeneration known as mandibular distraction osteogenesis (DO) in which a controlled mechanical stimulus promotes bone induction after an osteotomy and gradual separation of the osteotomy edges to examine the relationship between the mechanical environment, angiogenesis, and osteogenesis. MATERIALS AND METHODS: Adult Sprague-Dawley rats were treated with gradual distraction, gradual distraction plus the angiogenic inhibitor TNP-470, or acute distraction (a model of failed bony regeneration). Animals were killed at the end of distraction (day 13) or at the end of consolidation (day 41) and examined with muCT, histology, and immunohistochemistry for angiogenesis and bone formation (n = 4 per time-point per group). An additional group of animals (n = 6 per time-point per group) was processed for microarray analysis at days 5, 9, 13, 21, and 41. RESULTS AND CONCLUSIONS: Either TNP-470 administration or disruption of the mechanical environment prevented normal osteogenesis and resulted in a fibrous nonunion. Subsequent analysis of the regenerate showed an absence of angiogenesis by gross histology and immunohistochemical localization of platelet endothelial cell adhesion molecule in the groups that failed to heal. Microarray analysis revealed distinct patterns of expression of genes associated with osteogenesis, angiogenesis, and hypoxia in each of the three groups. Our findings confirm the interdependence of the mechanical environment, angiogenesis, and osteogenesis during DO, and suggest that induction of proangiogenic genes and the proper mechanical environment are both necessary to support new vasculature for bone induction in DO.

Angiogenesis Inhibitors↗

PubMed2005

Mechanobiology of mandibular distraction osteogenesis: finite element analyses with a rat model.

Three-dimensional finite element (FE) analyses were performed to characterize the local mechanical environment created within the tissue regenerate during mandibular distraction osteogenesis (DO) in a rat model. Finite element models were created from three-dimensional computed tomography image data of rat hemi-mandibles at four different time points during an optimal distraction osteogenesis protocol (i.e., most successful protocol for bone formation): end latency (post-operative day (POD) 5), distraction day 2 (POD 7), distraction day 5 (POD 10), and distraction day 8 (POD 13). A 0.25 mm distraction was simulated and the resulting hydrostatic stresses and maximum principal tensile strains were determined within the tissue regenerate. When compared to previous histological findings, finite element analyses showed that tensile strains up to 13% corresponded to regions of new bone formation and regions of periosteal hydrostatic pressure with magnitudes less than 17 kPa corresponded to locations of cartilage formation. Tensile strains within the center of the gap were much higher, leading us to conclude that tissue damage would occur there if the tissue was not compliant enough to withstand such high strains, and that this damage would trigger formation of new mesenchymal tissue. These data were consistent with histological evidence showing mesenchymal tissue present in the center of the gap throughout distraction. Finite element analyses performed at different time points during distraction were instrumental in determining the changes in hydrostatic stress and tensile strain fields throughout distraction, providing a mechanical environment rationale for the different levels of bone formation in end latency, and distraction day 2, 5, and 8 specimens.

Animals↗

PubMed2005

High-dose retinoic acid modulates rat calvarial osteoblast biology.

Retinoic acid has been shown to adversely affect craniofacial development. Cleft palate and craniosynostosis are two examples of craniofacial defects associated with prenatal exposure to this agent. Although the effects of retinoic acid on cephalic neural crest-derived tissues have previously been studied, the specific effects of retinoic acid on the cellular biology of osteoblasts remain unclear. The purpose of this study was to analyze in detail the effects of pharmacologic doses of retinoic acid on the differentiation and proliferation of osteoblasts derived from an intramembranous source. Primary rat calvarial osteoblasts were established in culture and treated with 1 or 10 microM all-trans-retinoic acid. Retinoic acid treatment markedly increased expression of osteopontin up to 48 h after stimulation. Consistent with this early stage of differentiation, both mRNA and protein analysis of FGF receptor isoforms demonstrated a switch in predominance from fibroblast growth factor receptor 2 (fgfr2) to fgfr1. Analysis of PCNA protein confirmed inhibition of proliferation by retinoic acid. To determine whether these alterations in osteoblast biology would lead to increased differentiation, we examined short term [alkaline phosphatase (AP) activity] and long term (von Kossa staining) surrogates of bone formation in vitro. These assays confirmed that retinoic acid increased osteogenesis, with a 4-fold increase in bone nodule formation in cells treated with 10 microM retinoic acid after 28 days. Overall, our results demonstrated that pharmacologic doses of all-trans-retinoic acid decreased osteoblast proliferation and increased differentiation, suggesting that retinoic acid may effect craniofacial development by pathologically enhancing osteogenesis.

Alkaline Phosphatase↗

PubMed2005

Mammalian fetal organ regeneration.

The developing fetus has the remarkable ability to heal dermal skin wounds by regenerating normal epidermis and dermis with restoration of the extracellular matrix architecture, strength, and function. The biology responsible for scarless wound healing in skin is a paradigm for ideal tissue repair. This regenerative capacity is lost in late gestation when fetal wounds heal with fibrosis and scar. Early in gestation, fetal skin is developing at a rapid pace in a unique environment. Investigation of normal skin embryogenesis and comparison between early scarless and late scarring fetal wounds has revealed distinct differences in inflammatory response, cellular mediators, wound contraction, cytokines, growth factors, and extracellular matrix modulators. The knowledge gained from comparative observational studies has served as a base for experimental interventions in animal models to induce or ameliorate scar. Although much progress has been made over the past decade, the mechanism of fetal wound healing remains largely unknown and attempts to mimic the scarless wound phenotype have not been completely successful. Identification of more key genes involved in skin regeneration may have implications in adult skin wounds and repair in other organ systems.

Animals↗

PubMed2005

New developments in pediatric plastic surgery research.

Pediatric plastic surgery research is a rapidly expanding field. Unique in many ways, researchers in this field stand at the union of multiple scientific specialties, including biomedical engineering, tissue engineering, polymer science, molecular biology, developmental biology, and genetics. The goal of this scientific effort is to translate research advances into improved treatments for children with congenital and acquired defects. Although the last decade has seen a dramatic acceleration in research related to pediatric plastic surgery, the next 10 years will no doubt lead to novel treatment strategies with improved clinical outcomes.

Animals↗