Role of TGF-ß3 in modulating inflammatory responses and wound healing processes in ischemic ulcers in atherosclerotic patients.

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-ß3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-ß3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-ß3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-ß3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-ß3 in order to evaluate its therapeutic effects. The expression pattern of TGF-ß3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-ß3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-ß3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-ß3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-ß3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.

Dynamic changes of cytokine profiles and virological markers during 48 weeks of entecavir treatment for HBeAg-positive chronic hepatitis B.

Objective: The aims of this study were to investigate the kinetic changes of serum, virological, and immunological markers during entecavir (ETV) antiviral therapy and to explore whether these indicators can predict the antiviral efficacy of ETV in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. Methods: HBeAg-positive CHB patients were enrolled and treated with ETV 0.5 mg/day. Clinical biochemical, virological, and serological tests were performed at baseline and every 12 weeks during the 48-week treatment. Plasma levels of cytokines (Flt-3L, IFN-α2, IFN-γ, IL-10, IL-17A, IL-6, TGF-ß1, TGF-ß2, TGF-ß3, and TNF-α) were measured at baseline and at 12 and 24 weeks after treatment. Analysis of the trends of these clinical indicators in ETV antiviral therapy was performed. Results: A total of 105 HBeAg-positive CHB patients were enrolled, and 100 of them completed 48 weeks of ETV treatment and follow-up. After 48 weeks of treatment, hepatitis B s antigen (HBsAg) decline ≥ 1 log10 was found in seven patients, but no patient achieved HBsAg disappearance. serological HBeAg disappeared in 13 patients, and serological HBeAg transformed in 3 patients. The baseline HBsAg and HBeAg levels, HBV DNA load, IL-10, and TGF-ß1 levels in the complete virological response group were lower than those in the incomplete virological response group, while the ALT level in the complete virological response group was higher than that in the incomplete virological response group. Both univariate analysis and multivariate analysis showed that baseline biochemical indexes, virological indexes, and cytokine levels had no correlation with the complete virological response at 48 weeks. In multivariate analysis, low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment (HBeAg OR = 1.003, 95% CI 1.001-1.006, p = 0.007; HBV DNA OR = 0.184, 95% CI 0.046-0.739, p = 0.017; IL-10 OR = 0.040, 95% CI 0.972-0.999, p = 0.040). Conclusion: Cytokine levels changed dynamically during ETV antiviral therapy. Low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment.

Evaluation of the Effects of Transforming Growth Factor-Beta 3 (TGF-ß3) Loaded Nanoparticles on Healing in a Rat Achilles Tendon Injury Model.

BACKGROUND: Achilles tendon (AT) midsubstance injuries may heal suboptimally, especially in athletes. Transforming growth factor-beta 3 (TGF-ß3) shows promise because of its recently discovered tendinogenic effects. Using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) may enhance the results by a sustained-release effect. HYPOTHESIS: The application of TGF-ß3 will enhance AT midsubstance healing, and the NP form will achieve better outcomes. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 80 rats underwent unilateral AT transection and were divided into 4 groups: (1) control (C); (2) empty chitosan film (Ch); (3) chitosan film containing free TGF-ß3 (ChT); and (4) chitosan film containing TGF-ß3-loaded NPs (ChN). The animals were sacrificed at 3 and 6 weeks. Tendons were evaluated for morphology (length and cross-sectional area [CSA]), biomechanics (maximum load, stress, stiffness, and elastic modulus), histology, immunohistochemical quantification (types I and III collagen [COL1 and COL3]), and gene expression (COL1A1, COL3A1, scleraxis, and tenomodulin). RESULTS: Morphologically, at 3 weeks, ChT (15 ± 2.7 mm) and ChN (15.6 ± 1.6 mm) were shorter than C (17.6 ± 1.8 mm) (P = .019 and = .004, respectively). At 6 weeks, the mean CSA of ChN (10.4 ± 1.9 mm2) was similar to that of intact tendons (6.4 ± 1.1 mm2) (P = .230), while the other groups were larger. Biomechanically, at 3 weeks, ChT (42.8 ± 4.9 N) had a higher maximum load than C (27 ± 9.1 N; P = .004) and Ch (29.2 ± 5.7 N; P = .005). At 6 weeks, ChN (26.9 ± 3.9 MPa) had similar maximum stress when compared with intact tendons (34.1 ± 7.8 MPa) (P = .121); the other groups were significantly lower. Histologically, at 6 weeks, the mean Movin score of ChN (4.5 ± 1.5) was lower than that of ChT (6.3 ± 1.8). Immunohistochemically, ChN had higher COL3 (1.469 ± 0.514) at 3 weeks and lower COL1 (1.129 ± 0.368) at 6 weeks. COL1A1 gene expression was higher in ChT and ChN at 3 weeks, but COL3A1 gene expression was higher in ChN. CONCLUSION: The application of TGF-ß3 had a positive effect on AT midsubstance healing, and the sustained-release NP form improved the outcomes, more specifically accelerating the remodeling process. CLINICAL RELEVANCE: This study demonstrated the effectiveness of TGF-ß3 on tendon healing on a rat model, which is an important step toward clinical use. The novel method of using PLGA-b-PEG NPs as a drug-delivery system with sustained-release properties had promising results.

Long Term Follow-Up of Pediatric Mandibular Reconstruction With Human Transforming Growth Factor-ß3.

Translating bone regeneration induced by recombinant human bone morphogenetic proteins from animal models to human patients has proven inexplicably inconsistent. This prompted us to test in 5 pediatric patients, an alternative osteoinductive morphogen, recombinant human transforming growth factor ß3 (hTGF-ß3), to reconstruct mandibular defects of such a size to preclude reconstruction with autologous bone. An osteoinductive implant of human demineralized bone matrix (DBM) loaded with 125 µg hTGF-ß3 per gram of DBM was implanted into one defect, and 250 µg hTGF-ß3 per gram of DBM in another. Thereafter in 3 patients limited amounts of particulate cortico-cancellous bone graft harvested from the posterior iliac crest were combined with 250 µg hTGF-ß3 per gram of DBM. Patients were followed up for 3 to 6 years. Three patients achieved clinically significant osteoinduction, 1 patient with hTGF-ß3 only, and 2 by combining hTGF-ß3 with a small supplement of autologous bone. One patient with hTGF-ß3 only and followed up for 5 years retains a viable reconstruction but has had sub-optimal bone regeneration. One patient had osteoinductive failure due to sepsis although the plate reconstruction remains viable. Recombinant human TGF-ß3 initiates osteoinduction in humans and potentiates autologous bone graft activity allowing the reconstruction of large mandibular defects in pediatric patients.

The effect of adipose-derived stem cells on enthesis healing after repair of acute and chronic massive rotator cuff tears in rats.

BACKGROUND: Chronic massive rotator cuff tears heal poorly and often retear. This study investigated the effect of adipose-derived stem cells (ADSCs) and transforming growth factor-ß3 (TGF-ß3) delivered in 1 of 2 hydrogels (fibrin or gelatin methacrylate [GelMA]) on enthesis healing after repair of acute or chronic massive rotator cuff tears in rats. METHODS: Adult male Lewis rats underwent bilateral transection of the supraspinatus and infraspinatus tendons with intramuscular injection of botulinum toxin A (n = 48 rats). After 8 weeks, animals received 1 of 8 interventions (n = 12 shoulders/group): (1) no repair, (2) repair only, or repair augmented with (3) fibrin, (4) GelMA, (5) fibrin + ADSCs, (6) GelMA + ADSCs, (7) fibrin + ADSCs + TGF-ß3, or (8) GelMA + ADSCs + TGF-ß3. An equal number of animals underwent acute tendon transection and immediate application of 1 of 8 interventions. Enthesis healing was evaluated 4 weeks after the repair by microcomputed tomography, histology, and mechanical testing. RESULTS: Increased bone loss and reduced structural properties were seen in chronic compared with acute tears. Bone mineral density of the proximal humerus was higher in repairs of chronic tears augmented with fibrin + ADSCs and GelMA + ADSCs than in unrepaired chronic tears. Similar improvement was not seen in acute tears. No intervention enhanced histologic appearance or structural properties in acute or chronic tears. CONCLUSIONS: Surgical repair augmented with ADSCs may provide more benefit in chronic tears compared with acute tears, although there was no added benefit to supplementing ADSCs with TGF-ß3.

[Experimental study on the transforming growth factor ß3 combined with dental pulp stem cells in early bone integration of implant].

Objective: To establish the experimental model of rabbit mandibular anterior implant repair and evaluate the effects of transforming growth factor (TGF)-ß3 and dental pulp stem cells (DPSC) in promoting the bone integration of implant. Methods: The New Zealand rabbits were randomly divided into experimental group, control group and blank group (6 rabbits for each group) . In the experimental group, the implant area was filled with the mixture of TGF-ß3, DPSC and Bio-oss powder. In the control group, the implant area was filled with the mixture of DPSC and Bio-oss powder. In the blank group, the implant area was filled with the mixture of phosphate buffer solution and Bio-oss powder. Eighteen New Zealand rabbits were sacrificed in 2 weeks after procedure. The treated alveolar bone tissue was observed. The bone tissue around the implant were estimated by HE staining, immunocytochemical staining and real-time quantitative PCR. Results: The implants were no shedding nor loose. HE staining shows the blank group had a sparse trabecular bone and a small amount of blood vessel around the implant and no obvious new bone formation. The control group showed that the bone trabecula around the implant was sparse and slender, the osteoblasts were arranged linearly around the trabecular bone, a small amount of new bone formation was found around the implant. In the experimental group, there were more thick and dense trabecular bone around the implant, the surrounding osteoblasts were arranged in clusters. The osteoblasts were active and many new bone formed. Typical bone lacunae, bone cells and a large number of new blood vessels can be observed. Immunohistochemistry showed that the proportion of average positive area in the experimental group, control group, blank group were (24.6±5.3) %, (11.3±2.8) % and (7.6±3.8) % respectively. The expression of bone sialoprotein in experimental group were significantly higher than the other 2 groups(P=0.000). Real-time quantitative PCR results showed that the expression level of Runt-related transcription factor 2 (RUNX2), type Ⅰcollagen (COL-Ⅰ), alkaline phosphatase in the experimental group was higher than in the blank group. The expression level of RUNX2 and COL-Ⅰ in the experimental group was higher than that of the control group (P=0.023). Conclusions: TGF-ß3 has potential to promote the transformation of DPSC into osteoblasts, which can promote the integration of bone around the implant.

Techniques for Optimizing Surgical Scars, Part 2: Hypertrophic Scars and Keloids.

Surgical management of benign or malignant cutaneous tumors may result in noticeable scars that are of great concern to patients, regardless of sex, age, or ethnicity. Techniques to optimize surgical scars are discussed in this three-part review. Part 2 focuses on scar revision for hypertrophic and keloids scars. Scar revision options for hypertrophic and keloid scars include corticosteroids, bleomycin, fluorouracil, verapamil, avotermin, hydrogel scaffold, nonablative fractional lasers, ablative and fractional ablative lasers, pulsed dye laser (PDL), flurandrenolide tape, imiquimod, onion extract, silicone, and scar massage.

[Experimental study of transforming growth factor-ß3 combined with dental pulp stem cells in promoting the implant's osseointegration].

Objective: To investigate the effect of transforming growth factor-ß3 (TGF-ß3) and dental pulp stem cells (DPSC) in promoting the implant's osteointegration. Methods: Thirty-three New Zealand white rabbits were randomly divided into phosphate buffer saline (PBS) group, DPSC group and TGF-ß3 + DPSC group (12 rabbits/group). Two teeth from the rabbits's mandibular incisors or molars were pulled out randomly, then implant were placed in the tooth extraction site immediately. In PBS group, the implant area was filled with Bio-Oss powder 0.30 g mixed by PBS 20 µl only; while the implant area was filled with Bio-oss powder 0.30 g and 1×10(8)/L DPSC 20 µl in DPSC group; in the the TGF-ß3+DPSC group the implant area was filled with Bio-Oss powder 0.30 g mixed with 1×10(8)/L DPSC 20 µl and 80 µg/L TGF-ß3 20 µl. Eighteen New Zealand rabbits were executed in the 4 weeks and 8 weeks respectively. The treated alveolar bone tissue and implant were collected for plastic section. Alizarin red staining (ARS), immunohistochemical detection (IHC) of bone sialoprotein (BSP), osteocalcin (OC) and type Ⅰ collagen (COL-Ⅰ) were performed after 4 weeks and 8 weeks. Combined bone lamelta width (CBLW) and implant bone contact rate (IBCR), trabecular width (TW) and trabecular area percentage (TA) were observed by histomorphometric measurement. Results: ARS staining: 4 weeks after the operation, the TGF-ß3+ DPSC group showed more red calcified nodules than the other two groups; 8 weeks after operation, the red calcified nodule was further increased. 4 weeks after the operation, the expression of BSP, OC and COL-Ⅰ was (0.35± 0.04), (0.36 ± 0.03) and (0.39 ± 0.01) respectively in TGF-ß3+ DPSC group, (0.27 ± 0.02), (0.24 ± 0.01) and (0.28±0.03) respectively in DPSC group, and (0.13±0.03), (0.15±0.02) and (0.16±0.02) respectively in PBS group. Eight weeks after operation, the expression of BSP, OC and COL-Ⅰ was (0.51±0.02), (0.49±0.03) and (0.53±0.02) respectively in TGF-ß3+DPSC group, (0.35±0.02), (0.37±0.01) and (0.38±0.01) respectively in DPSC group, and (0.21±0.03), (0.19±0.01) and (0.22±0.02) respectively in PBS group. After 4 weeks and 8 weeks, the expression of BSP, OC and COL-Ⅰ in TGF-ß3+DPSC group were significantly higher than the other groups (P<0.05), there was no significant difference between DPSC group and PBS group (P>0.05). Eight weeks after operation, the CBLW, IBCR, TW and TA around implant in TGF-ß3+ DPSC group were significantly higher than that in the other groups (P<0.05), there was no significant difference between DPSC group and PBS group (P>0.05). Conclusions: The DPSC has the potential osteogenic differentiation ability; TGF-ß3 can accelerate the osteogenic differentiation of DPSC to some extent; TGF-ß3 combined with DPSC can effectively promote the implant's osseointegration.

Cementogenesis and osteogenesis in periodontal tissue regeneration by recombinant human transforming growth factor-ß3 : a pilot study in Papio ursinus.

OBJECTIVES: The aim of this study was to investigate cementogenesis and alveolar bone induction during in vivo periodontal tissue regeneration upon implantation of hTGF-ß3 in furcation defects of Papio ursinus and to evaluate the feasibility of gene expression studies. MATERIALS AND METHODS: Class II furcation defects (day 0) were prepared in mandibular first and second molars of three P. ursinus and on day 30 implanted with and without 75 µg hTGF-ß3 in Matrigel® matrix. On day 0, 30 and 90, cementum and alveolar bone were harvested for gene expression analyses. Coral-derived bioreactors with and without 250 µg hTGF-ß3 were implanted in the rectus abdominis to monitor tissue induction. RESULTS: hTGF-ß3 induced cementogenesis with TGF-ß3 , Cementum Protein-1 (Cemp1) and Osteocalcin (OC) up-regulation, and down-regulation of BMP-2 and OP-1. Matrigel® matrix specimens showed up-regulation of BMP-2, TGF-ß3 , and OC, with down-regulation of OP-1 and Cemp1. hTGF-ß3 induced alveolar bone with down-regulation of OP-1, TGF-ß3 , OC, and Cemp1. hTGF-ß3 bioreactors induced bone at the periphery only. BMP-3, BMP-4, TGF-ß1 and TGF-ß3 were up-regulated in the adjacent muscle with TGF-ß2 down-regulation. CONCLUSIONS: Cementogenesis and osteogenesis by hTGF-ß3 entail the expression and up-regulation of TGF-ß3 and OC with fine tuning and modulation of BMP-2 and OP-1.

PLGA-based microcarriers induce mesenchymal stem cell chondrogenesis and stimulate cartilage repair in osteoarthritis.

In the present study, we aimed at evaluating the ability of novel PLGA-P188-PLGA-based microspheres to induce the differentiation of mesenchymal stem/stromal cells (MSC) into chondrocytes. To this aim, we tested microspheres releasing TGFß3 (PAM-T) in vitro and in situ, in a pathological osteoarthritic (OA) environment. We first evaluated the chondrogenic differentiation of human MSCs seeded onto PAM-T in vitro and confirmed the up-regulation of chondrogenic markers while the secretome of the cells was not changed by the 3D environment. We then injected human MSC seeded onto PAM-T in the knee joints of mice with collagenase-induced OA. After 6 weeks, histological analysis revealed that formation of a cartilage-like tissue occurred at the vicinity of PAM-T that was not observed when MSCs were seeded onto PAM. We also noticed that the endogenous articular cartilage was less degraded. The extent of cartilage protection was further analysed by confocal laser microscopy. When MSCs seeded onto PAM-T were injected early after OA induction, protection of cartilage against degradation was evidenced and this effect was associated to a higher survival of MSCs in presence of TGFß3. This study points to the interest of using MSCs seeded onto PAM for cartilage repair and stimulation of endogenous cartilage regeneration.

Tissue segregation restores the induction of bone formation by the mammalian transforming growth factor-ß(3) in calvarial defects of the non-human primate Papio ursinus.

A diffusion molecular hypothesis from the dura and/or the leptomeninges below that would control the induction of calvarial membranous bone formation by the recombinant human transforming growth factor-ß3 (hTGF-ß3) was investigated. Coral-derived calcium carbonate-based macroporous constructs (25 mm diameter; 3.5/4 mm thickness) with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) were inserted into forty calvarial defects created in 10 adult Chacma baboons Papio ursinus. In 20 defects, an impermeable nylon foil membrane (SupraFOIL(®)) was inserted between the cut endocranial bone and the underlying dura mater. Twenty of the macroporous constructs were preloaded with hTGF-ß3 (125 µg in 1000 µl 20 mM sodium succinate, 4% mannitol pH4.0), 10 of which were implanted into defects segregated by the SupraFOIL(®) membrane, and 10 into non-segregated defects. Tissues were harvested on day 90, processed for decalcified and undecalcified histology and quantitative real-time polymerase chain reaction (qRT-PCR). Segregated untreated macroporous specimens showed a reduction of bone formation across the macroporous spaces compared to non-segregated constructs. qRT-PCR of segregated untreated specimens showed down regulation of osteogenic protein-1 (OP-1), osteocalcin (OC), bone morphogenetic protein-2 (BMP-2), RUNX-2 and inhibitor of DNA binding-2 and -3 (ID2,ID3) and up regulation of TGF-ß3, a molecular signalling pathway inhibiting the induction of membranous bone formation. Non-segregated hTGF-ß3/treated constructs also showed non-osteogenic expression profiles when compared to non-segregated untreated specimens. Segregated hTGF-ß3/treated 7% HA/CC constructs showed significantly greater induction of bone formation across the macroporous spaces and, compared to non-segregated hTGF-ß3/treated constructs, showed up regulation of OP-1, OC, BMP-2, RUNX-2, ID2 and ID3. Similar up-regulated expression profiles were seen for untreated non-segregated constructs. TGF-ß signalling via ID genes creates permissive or refractory micro-environments that regulate the induction of calvarial bone formation which is controlled by the exogenous hTGF-ß3 upon segregation of the calvarial defects. The dura is the common regulator of the induction of calvarial bone formation modulated by the presence or absence of the SupraFOIL(®) membrane with or without hTGF-ß3.

Transforming growth factor beta (TGF-ß) isoforms in wound healing and fibrosis.

Scar formation, with persistent alteration of the normal tissue structure, is an undesirable and significant result of both wound healing and fibrosing disorders. There are few strategies to prevent or to treat scarring. The transforming growth factor beta (TGF-ß) superfamily is an important mediator of tissue repair. Each TGF-ß isoform may exert a different effect on wound healing, which may be context-dependent. In particular, TGF-ß1 may mediate fibrosis in adults' wounds, while TGF-ß3 may promote scarless healing in the fetus and reduced scarring in adults. Thus, TGF-ß3 may offer a scar-reducing therapy for acute and chronic wounds and fibrosing disorders.

Demineralized bone matrix combined bone marrow mesenchymal stem cells, bone morphogenetic protein-2 and transforming growth factor-ß3 gene promoted pig cartilage defect repair.

OBJECTIVES: To investigate whether a combination of demineralized bone matrix (DBM) and bone marrow mesenchymal stem cells (BMSCs) infected with adenovirus-mediated- bone morphogenetic protein (Ad-BMP-2) and transforming growth factor-ß3 (Ad-TGF-ß3) promotes the repair of the full-thickness cartilage lesions in pig model. METHODS: BMSCs isolated from pig were cultured and infected with Ad-BMP-2(B group), Ad-TGF-ß3 (T group), Ad-BMP-2 + Ad-TGF-ß3(BT group), cells infected with empty Ad served as a negative group(N group), the expression of the BMP-2 and TGF-ß3 were confirmed by immunofluorescence, PCR, and ELISA, the expression of SOX-9, type II collagen(COL-2A), aggrecan (ACAN) in each group were evaluated by real-time PCR at 1w, 2w, 3w, respectively. The chondrogenic differentiation of BMSCs was evaluated by type II collagen at 21d with immunohistochemical staining. The third-passage BMSCs infected with Ad-BMP-2 and Ad-TGF-ß3 were suspended and cultured with DBM for 6 days to construct a new type of tissue engineering scaffold to repair full-thickness cartilage lesions in the femur condyles of pig knee, the regenerated tissue was evaluated at 1,2 and 3 months after surgery by gross appearance, H&E, safranin O staining and O'driscoll score. RESULTS: Ad-BMP-2 and Ad-TGF-ß3 (BT group) infected cells acquired strong type II collagen staining compared with Ad-BMP-2 (B group) and Ad-TGF-ß3 (T group) along. The Ad-BMP-2 and Ad-TGF-ß3 infected BMSCs adhered and propagated well in DBM and the new type of tissue engineering scaffold produced hyaline cartilage morphology containing a stronger type II collagen and safranin O staining, the O'driscoll score was higher than other groups. CONCLUSIONS: The DBM compound with Ad-BMP-2 and Ad-TGF-ß3 infected BMSCs scaffold has a good biocompatibility and could well induce cartilage regeneration to repair the defects of joint cartilage. This technology may be efficiently employed for cartilage lesions repair in vivo.

Scar prevention and remodeling: a review of the medical, surgical, topical and light treatment approaches.

Cosmetic, functional, and structural sequelae of scarring are innumerable, and measures exist to optimize and ultimately minimize these sequelae. To evaluate the innumerable methods available to decrease the cosmetic, functional, and structural repercussions of scarring, pubMed search of the English literature with key words scar, scar revision, scar prevention, scar treatment, scar remodeling, cicatrix, cicatrix treatment, and cicatrix remodeling was done. Original articles and reviews were examined and included. Seventy-nine manuscripts were reviewed. Techniques, comparisons, and results were reviewed and tabulated. Overall, though topical modalities are easier to use and are usually more attractive to the patient, the surgical approaches still prove to be superior and more reliable. However, advances in topical medications for scar modification are on the rise and a change towards medical treatment of scars may emerge as the next best approach. Comparison studies of the innumerable specific modalities for scar revision and prevention are impossible. Standardization of techniques is lacking. Scarring, the body's natural response to a wound, can create many adverse effects. At this point, the practice of sound, surgical fundamentals still trump the most advanced preventative methods and revision techniques. Advances in medical approaches are available, however, to assist the scarring process, which even the most advanced surgical fundamentals will ultimately lead to. Whether through newer topical therapies, light treatment, or classical surgical intervention, our treatment armamentarium of scars has expanded and will allow us to maximize scar prevention and to minimize scar morbidity.

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model.

BACKGROUND CONTEXT: Lumbar discectomies are common surgical interventions that treat radiculopathy by removing herniated and loose intervertebral disc (IVD) tissues. However, remaining IVD tissue can continue to degenerate resulting in long-term clinical problems. Little information is available on the effects of discectomy on IVD biology. Currently, no treatments exist that can suspend or reverse the degeneration of the remaining IVD. PURPOSE: To improve the knowledge on how discectomy procedures influence IVD physiology and to assess the potential of growth factor treatment as an augmentation during surgery. STUDY DESIGN: To determine effects of discectomy on IVDs with and without transforming growth factor beta 3 (TGFß3) augmentation using bovine IVD organ culture. METHODS: This study determined effects of discectomy with and without TGFß3 injection using 1-, 6-, and 19-day organ culture experiments. Treated IVDs were injected with 0.2 µg TGFß3 in 20 µL phosphate-buffered saline+bovine serum albumin into several locations of the discectomy site. Cell viability, gene expression, nitric oxide (NO) release, IVD height, aggrecan degradation, and proteoglycan content were determined. RESULTS: Discectomy significantly increased cell death, aggrecan degradation, and NO release in healthy IVDs. Transforming growth factor beta 3 injection treatment prevented or mitigated these effects for the 19-day culture period. CONCLUSIONS: Discectomy procedures induced cell death, catabolism, and NO production in healthy IVDs, and we conclude that post-discectomy degeneration is likely to be associated with cell death and matrix degradation. Transforming growth factor beta 3 injection augmented discectomy procedures by acting to protect IVD tissues by maintaining cell viability, limiting matrix degradation, and suppressing NO. We conclude that discectomy procedures can be improved with injectable therapies at the time of surgery although further in vivo and human studies are required.

Scar revision review.

Scars are a natural part of dermal healing following lacerations, incisions, or tissue loss. They can vary in quality depending on the individual's racial characteristics, the mechanism of the trauma, and conditions in which the wound healed-all of which are factors beyond the surgeon's control. A scar on the face can have significant implications for the patient. What may seem like an insignificant issue to the casual observer can cause continuous frustration for the patient, affecting their daily lives. These can include psychological as well as social consequences, leading to a diminished quality of life. Factors that the surgeon can control include the favorable repositioning of the scar, proper alignment of the wound edges, and meticulous handling of the tissues.

Transforming growth factor ß3 for the prevention of vocal fold scarring.

OBJECTIVES/HYPOTHESIS: Vocal fold scarring poses a therapeutic challenge. It causes hoarseness and decreases the quality of life. Transforming growth factor ß3 (TGFß3) is highly expressed in fetal wounds that heal without scarring, and administration of TGFß3 has been reported to prevent scarring of the skin and the buccal mucosa. Thus TGFß3 is considered to be a key molecule in scar-free healing. This study aimed to examine the ability of TGFß3 to prevent vocal fold scarring, with particular attention paid to the distribution of extracellular matrices and functional outcomes. STUDY DESIGN: Prospective study using an animal model. METHODS: Ten beagles were used in this study; 500 µL of TGFß3 (0.5 µg/mL: 5 beagles) or saline (5 beagles) was injected into the vocal fold lamina propria. Fifteen minutes after injection, vocal folds were injured by stripping off the entire layer of the lamina propria. Six months after surgery, animals were euthanized and the larynges were harvested. Vibratory and histologic examinations were performed. RESULTS: The administration of TGFß3 suppressed granulation-tissue formation and scarring. TGFß3-treated vocal folds showed significantly better vibratory properties, resembling normal vocal folds. Histologic analysis revealed favorable restoration of elastin and hyaluronic acid in the lamina propria. The distribution of collagen was well organized, and collagen deposition was less dense in TGFß3-treated vocal folds compared to sham-treated vocal folds. CONCLUSIONS: Administration of TGFß3 before injury significantly suppressed scar formation and induced favorable restoration of extracellular matrices in the vocal fold lamina propria, resulting in much improved phonatory function.

Synergistic induction of periodontal tissue regeneration by binary application of human osteogenic protein-1 and human transforming growth factor-ß3 in Class II furcation defects of Papio ursinus.

BACKGROUND AND OBJECTIVE: Binary applications of recombinant human osteogenic protein-1 (hOP-1) and transforming growth factor-ß3 (hTGF-ß3) synergize to induce pronounced bone formation. To induce periodontal tissue regeneration, binary applications of hOP-1 and hTGF-ß(3) were implanted in Class II furcation defects of the Chacma baboon, Papio ursinus. MATERIAL AND METHODS: Defects were created bilaterally in the furcation of the first and second mandibular molars of three adult baboons. Single applications of 25 µg hOP-1 and 75 µg hTGF-ß(3) in Matrigel(®) matrix were compared with 20:1 binary applications, i.e. 25 µg hOP-1 and 1.25 µg hTGF-ß(3). Morcellated fragments of autogenous rectus abdominis striated muscle were added to binary applications. Sixty days after implantation, the animals were killed and the operated tissues harvested en bloc. Undecalcified sections were studied by light microscopy, and regenerated tissue was assessed by measuring volume and height of newly formed alveolar bone and cementum. RESULTS: The hOP-1 and hTGF-ß(3) induced periodontal tissue regeneration and cementogenesis. Qualitative morphological analysis of binary applications showed clear evidence for considerable periodontal tissue regeneration. Quantitatively, the differences in the histomorphometric values did not reach statistical significance for the group size chosen for this primate study. The addition of morcellated muscle fragments did not enhance tissue regeneration. Binary applications showed rapid expansion of the newly formed bone against the root surfaces following fibrovascular tissue induction in the centre of the treated defects. CONCLUSION: Binary applications of hOP-1 and hTGF-ß(3) in Matrigel(®) matrix in Class II furcation defects of P. ursinus induced substantial periodontal tissue regeneration, which was tempered, however, by the anatomy of the furcation defect model, which does not allow for the rapid growth and expansion of the synergistic induction of bone formation, particularly when additionally treated with responding myoblastic stem cells.

Regenerative potential of TGFß3 + Dex and notochordal cell conditioned media on degenerated human intervertebral disc cells.

Injection of soluble cell signaling factors into degenerated intervertebral discs (IVDs) offers a minimally invasive treatment that could limit the processes of degeneration by stimulating native matrix repair. This study evaluated the regenerative capacity of degenerated nucleus pulposus (NP) cells obtained from patients undergoing anterior interbody fusions by measuring metabolic activity, DNA content, glycosaminoglycan (GAG) content, and cellular phenotype using qRT-PCR profiling with a custom array of 42 genes. NP cells were cultured in alginate for 7 days with 4 treatment groups: transforming growth factor beta 3 (TGFß3) + dexamethasone (Dex), soluble factors released from notochordal cells (NCs) cultured in alginate (NCA), soluble factors released from NCs in their native tissue environment (NCT), and basal media. TGFß3 + Dex stimulated degenerated human NP cells to proliferate and exhibit an anti-catabolic gene expression profile (with a decrease in ADAMTS5 and MMP1 compared to basal, and an increase in SOX9, decrease in ADAMTS5, MMP1, collagen I and collagen III compared to day 0), while NCA stimulated the greatest GAG per cell. We conclude that degenerated human NP cells exhibit regenerative potential, and that an optimal treatment will likely require treatments, such as TGFß3 + Dex, which were able to increase cell metabolism and reduce catabolism, as well as treatments with factors found in NC conditioned medium, that were able to produce high amounts of GAG per cell. Additional studies to optimize NC culture conditions are required to determine if NC conditioned medium can be made with the capacity to enhance NP cell proliferation and metabolism.