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Journal of Periodontology Dec 2022The use of biologics may be indicated for alveolar ridge preservation (ARP) and reconstruction (ARR), and implant site development (ISD). The present systematic review...
BACKGROUND
The use of biologics may be indicated for alveolar ridge preservation (ARP) and reconstruction (ARR), and implant site development (ISD). The present systematic review aimed to analyze the effect of autologous blood-derived products (ABPs), enamel matrix derivative (EMD), recombinant human platelet-derived growth factor-BB (rhPDGF-BB), and recombinant human bone morphogenetic protein-2 (rhBMP-2), on the outcomes of ARP/ARR and ISD therapy (i.e., alveolar ridge augmentation [ARA] and maxillary sinus floor augmentation [MSFA]).
METHODS
An electronic search for eligible articles published from January 2000 to October 2021 was conducted. Randomized clinical trials evaluating the efficacy of ABPs, EMD, rhBMP-2, and rhPDGF-BB for ARP/ARR and ISD were included according to pre-established eligibility criteria. Data on linear and volumetric dimensional changes, histomorphometric findings, and a variety of secondary outcomes (i.e., clinical, implant-related, digital imaging, safety, and patient-reported outcome measures [PROMs]) were extracted and critically analyzed. Risk of bias assessment of the selected investigations was also conducted.
RESULTS
A total of 39 articles were included and analyzed qualitatively. Due to the high level of heterogeneity across studies, quantitative analyses were not feasible. Most studies in the topic of ARP/ARR revealed that the use of biologics rendered similar results compared with conventional protocols. However, when juxtaposed to unassisted healing or socket filling using collagen sponges, the application of biologics did contribute to attenuate post-extraction alveolar ridge atrophy in most investigations. Additionally, histomorphometric outcomes were positively influenced by the application of biologics. The use of biologics in ARA interventions did not yield superior clinical or radiographic outcomes compared with control therapies. Nevertheless, ABPs enhanced new bone formation and reduced the likelihood of early wound dehiscence. The use of biologics in MSFA interventions did not translate into superior clinical or radiographic outcomes. It was observed, though, that the use of some biologics may promote bone formation during earlier stages of healing. Only four clinical investigations evaluated PROMs and reported a modest beneficial impact of the use of biologics on pain and swelling. No severe adverse events in association with the use of the biologics evaluated in this systematic review were noted.
CONCLUSIONS
Outcomes of therapy after post-extraction ARP/ARR and ARA in edentulous ridges were comparable among different therapeutic modalities evaluated in this systematic review. Nevertheless, the use of biologics (i.e., PRF, EMD, rhPDGF-BB, and rhBMP-2) in combination with a bone graft material generally results into superior histomorphometric outcomes and faster wound healing compared with control groups.
Topics: Humans; Tooth Socket; Sinus Floor Augmentation; Biological Products; Becaplermin; Alveolar Ridge Augmentation; Alveolar Process; Tooth Extraction
PubMed: 35841608
DOI: 10.1002/JPER.22-0069 -
Journal of Diabetes and Its... 2014The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular pathway interactions of these markers found to be consistently associated with DR. Relevant databases [PubMed and ISI web of science] were searched for all published articles investigating molecular biomarkers of the vitreous associated with DR. Based on set exclusion/inclusion criteria available data from studies with human vitreous samples were extracted and used for our meta-analysis. The interactions of significant biomarkers in DR were investigated via STRING and KEGG pathway analysis. Our meta-analysis of DR identifies eleven biomarkers as potential therapeutic candidates alternate to current anti-VEGF therapy. Four of these are deemed viable therapeutic targets for PDR; ET receptors (ET A and ET B), anti-PDGF-BB, blocking TGF-β using cell therapy and PEDF. The identification of supplementary or synergistic therapeutic candidates to anti VEGF in the treatment of DR may aid in the development of future treatment trials.
Topics: Becaplermin; Biomarkers; Diabetic Retinopathy; Humans; Proto-Oncogene Proteins c-sis; Receptor, Endothelin A; Receptor, Endothelin B; Transforming Growth Factor beta; Vitreous Body
PubMed: 24630762
DOI: 10.1016/j.jdiacomp.2013.09.010 -
Medicina (Kaunas, Lithuania) Mar 2023Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of... (Review)
Review
Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of periodontal regeneration, both in research and clinical practice. Outcomes of histologic studies are particularly valuable when interpreted considering additional evidence available from pre-clinical and clinical studies. One of the best-documented growth factors areproven to have positive effects on a myriad of oral regenerative procedures is recombinant human platelet-derived growth factor-BB (rhPDGF-BB). While a systematic review of clinical studies evaluating rhPDGF in oral regenerative procedures has been recently completed, a review article that focuses on the histologic outcomes is needed. Hence, this communication discusses the histologic effects of rhPDGF-BB on oral and periodontal regenerative procedures, including root coverage and soft tissue augmentation, intrabony defects, furcation defects, peri-implant bone augmentation, and guided bone regeneration. Studies from 1989 to 2022 have been included in this review.
Topics: Humans; Becaplermin; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Intercellular Signaling Peptides and Proteins; Furcation Defects
PubMed: 37109634
DOI: 10.3390/medicina59040676 -
Scientific Reports Mar 2017The prognosis for successful treatment of periodontal diseases is generally poor. Current therapeutic strategies often fail to regenerate infected periodontium. Recently... (Meta-Analysis)
Meta-Analysis Review
The prognosis for successful treatment of periodontal diseases is generally poor. Current therapeutic strategies often fail to regenerate infected periodontium. Recently an alternative strategy has been developed that combines conventional treatment with the application of recombinant human growth factors (rhGFs). But ambiguities in existed studies on the clinical efficacy of rhGFs do not permit either the identification of the specific growth factors effective for therapeutic interventions or the optimal concentration of them. Neither is it known whether the same rhGF can stimulate regeneration of both soft tissue and bone, or whether different patient populations call for differential use of the growth factors. In order to explore these issues, a meta-analysis was carried out. Particular attention was given to the therapeutic impact of fibroblast growth factor 2(FGF-2) and platelet derived growth factor BB (PDGF-BB). Our findings indicate that 0.3% rhFGF-2 and 0.3 mg/ml rhPDGF-BB show a greater capacity for periodontal regeneration than other concentrations and superiority to control groups with statistical significance. In the case of patients suffering only from gingival recession, however, the application of rhPDGF-BB produces no significant regenerative advantage. The findings of this study can potentially endow clinicians with guidelines for the appropriate application of these two rhGFs.
Topics: Becaplermin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fibroblast Growth Factor 2; Humans; Periodontal Diseases; Periodontium; Proto-Oncogene Proteins c-sis; Randomized Controlled Trials as Topic; Recombinant Proteins; Regeneration; Treatment Outcome
PubMed: 28246406
DOI: 10.1038/s41598-017-00113-y -
The Cochrane Database of Systematic... Oct 2015Foot ulcers are a major complication of diabetes mellitus, often leading to amputation. Growth factors derived from blood platelets, endothelium, or macrophages could... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Foot ulcers are a major complication of diabetes mellitus, often leading to amputation. Growth factors derived from blood platelets, endothelium, or macrophages could potentially be an important treatment for these wounds but they may also confer risks.
OBJECTIVES
To assess the benefits and harms of growth factors for foot ulcers in patients with type 1 or type 2 diabetes mellitus.
SEARCH METHODS
In March 2015 we searched the Cochrane Wounds Group Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations, Ovid EMBASE and EBSCO CINAHL. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
Randomised clinical trials in any setting, recruiting people with type 1 or type 2 diabetes mellitus diagnosed with a foot ulcer. Trials were eligible for inclusion if they compared a growth factor plus standard care (e.g., antibiotic therapy, debridement, wound dressings) versus placebo or no growth factor plus standard care, or compared different growth factors against each other. We considered lower limb amputation (minimum of one toe), complete healing of the foot ulcer, and time to complete healing of the diabetic foot ulcer as the primary outcomes.
DATA COLLECTION AND ANALYSIS
Independently, we selected randomised clinical trials, assessed risk of bias, and extracted data in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We subjected our analyses to both fixed-effect and random-effects model analyses.
MAIN RESULTS
We identified 28 randomised clinical trials involving 2365 participants. The cause of foot ulcer (neurologic, vascular, or combined) was poorly defined in all trials. The trials were conducted in ten countries. The trials assessed 11 growth factors in 30 comparisons: platelet-derived wound healing formula, autologous growth factor, allogeneic platelet-derived growth factor, transforming growth factor β2, arginine-glycine-aspartic acid peptide matrix, recombinant human platelet-derived growth factor (becaplermin), recombinant human epidermal growth factor, recombinant human basic fibroblast growth factor, recombinant human vascular endothelial growth factor, recombinant human lactoferrin, and recombinant human acidic fibroblast growth factor. Topical intervention was the most frequent route of administration. All the trials were underpowered and had a high risk of bias. Pharmaceutical industry sponsored 50% of the trials.Any growth factor compared with placebo or no growth factor increased the number of participants with complete wound healing (345/657 (52.51%) versus 167/482 (34.64%); RR 1.51, 95% CI 1.31 to 1.73; I(2) = 51%, 12 trials; low quality evidence). The result is mainly based on platelet-derived wound healing formula (36/56 (64.28%) versus 7/27 (25.92%); RR 2.45, 95% 1.27 to 4.74; I(2) = 0%, two trials), and recombinant human platelet-derived growth factor (becaplermin) (205/428 (47.89%) versus 109/335 (32.53%); RR 1.47, 95% CI 1.23 to 1.76, I(2)= 74%, five trials).In terms of lower limb amputation (minimum of one toe), there was no clear evidence of a difference between any growth factor and placebo or no growth factor (19/150 (12.66%) versus 12/69 (17.39%); RR 0.74, 95% CI 0.39 to 1.39; I(2) = 0%, two trials; very low quality evidence). One trial involving 55 participants showed no clear evidence of a difference between recombinant human vascular endothelial growth factor and placebo in terms of ulcer-free days following treatment for diabetic foot ulcers (RR 0.64, 95% CI 0.14 to 2.94; P value 0.56, low quality of evidence)Although 11 trials reported time to complete healing of the foot ulcers in people with diabetes , meta-analysis was not possible for this outcome due to the unique comparisons within each trial, failure to report data, and high number of withdrawals. Data on quality of life were not reported. Growth factors showed an increasing risk of overall adverse event rate compared with compared with placebo or no growth factor (255/498 (51.20%) versus 169/332 (50.90%); RR 0.83; 95% CI 0.72 to 0.96; I(2) = 48%; eight trials; low quality evidence). Overall, safety data were poorly reported and adverse events may have been underestimated.
AUTHORS' CONCLUSIONS
This Cochrane systematic review analysed a heterogeneous group of trials that assessed 11 different growth factors for diabetic foot ulcers. We found evidence suggesting that growth factors may increase the likelihood that people will have complete healing of foot ulcers in people with diabetes. However, this conclusion is based on randomised clinical trials with high risk of systematic errors (bias). Assessment of the quality of the available evidence (GRADE) showed that further trials investigating the effect of growth factors are needed before firm conclusions can be drawn. The safety profiles of the growth factors are unclear. Future trials should be conducted according to SPIRIT statement and reported according to the CONSORT statement by independent investigators and using the Foundation of Patient-Centered Outcomes Research recommendations.
Topics: Amputation, Surgical; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Foot; Growth Substances; Humans; Randomized Controlled Trials as Topic; Wound Healing
PubMed: 26509249
DOI: 10.1002/14651858.CD008548.pub2 -
Cureus Jul 2022Diabetes is a leading chronic illness in the modern world and 19-34% develop chronic diabetic foot ulcers (DFUs) in their lifetime, often necessitating amputation. The... (Review)
Review
Diabetes is a leading chronic illness in the modern world and 19-34% develop chronic diabetic foot ulcers (DFUs) in their lifetime, often necessitating amputation. The reduction in tissue growth factors and resulting imbalance between proteolytic enzymes and their inhibitors, along with systemic factors impairing healing appear particularly important in chronic wounds. Growth factors applied topically have thus been suggested to be a non-invasive, safe, and cost-effective adjunct to improve wound healing and prevent complications. Comprehensive database searches of MEDLINE via PubMed, EMBASE, Cochrane, and ClinicalTrials.gov were performed to identify clinical evidence and ongoing trials. The risk of bias analysis included randomized controlled trials (RCTs) was performed using the Cochrane Risk of Bias 2.0 tool. We included randomized controlled trials that compared the use of a topical biologic growth factor-containing regimen to any other regimen. Primary outcomes of interest were time to wound closure, healing rate, and time. Secondary outcomes included the incidence of adverse events such as infection. A total of 41 trials from 1992-2020 were included in this review, with a total recorded 3,112 patients. Platelet-derived growth factors (PDGF) in the form of becaplermin gel are likely to reduce the time of closure, increase the incidence of wound closure, and complete wound healing. Human umbilical cord-related treatments, dehydrated human amnion and chorion allograft (dHACA), and hypothermically stored amniotic membrane (HSAM), consistently increased the rates and incidence of complete ulcer healing while reducing ulcer size and time to complete ulcer healing. Fibroblast growth factor-1 (FGF1) showed only a slight benefit in multiple studies regarding increasing complete ulcer healing rates and incidence while reducing ulcer size and time to complete ulcer healing, with a few studies showing no statistical difference from placebo. Platelet-rich fibrin (PRF) is consistent in reducing the time to complete ulcer healing and increasing wound healing rate but may not reduce ulcer size or increase the incidence of complete ulcer healing. Targeting the wound healing pathway via the extrinsic administration of growth factors is a promising option to augment wound healing in diabetic patients. Growth factors have also shown promise in specific subgroups of patients who are at risk of significantly impaired wound healing such as those with a history of secondary infection and vasculopathy. As diabetes impairs multiple stages of wound healing, combining growth factors in diabetic wound care may prove to be an area of interest. Evidence from this systematic literature review suggests that topical adjuncts probably reduce time to wound closure, reduce healing time, and increase the healing rate in patients with chronic DFUs.
PubMed: 36035037
DOI: 10.7759/cureus.27180 -
Journal of Clinical Periodontology Mar 2015The aim was to evaluate the effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human fibroblast growth factor-2 (rhFGF-2) on... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
The aim was to evaluate the effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human fibroblast growth factor-2 (rhFGF-2) on treating periodontal intra-bony defects, compared to the control (carrier alone).
METHODS
Electronic and hand searches were performed to identify eligible studies. The weighed mean differences of linear defect fill (LDF), probing depth (PD) reduction, clinical attachment level (CAL) gain and gingival recession (GR) were calculated using random effect meta-analysis.
RESULTS
The searches yielded 1018 articles, of which seven studies were included. Only one included study was considered at low risk of bias. The outcomes that reached statistical significance in comparison to carriers alone included: LDF (0.95 mm, 95% CI: 0.62-1.28 mm or 20.17%, 95% CI: 11.81-28.54%) and CAL gain (0.34 mm, 95% CI: 0.03-0.65 mm) for PDGF, and LDF (21.22%, 95% CI: 5.82-36.61%) for FGF-2.
CONCLUSIONS
Within the limits of this review, rhPDGF-BB demonstrated significantly more LDF and CAL gain; rhFGF-2 resulted in significantly higher percentage of LDF.
Topics: Alveolar Bone Loss; Becaplermin; Bone Regeneration; Fibroblast Growth Factor 2; Gingival Recession; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Attachment Loss; Periodontal Pocket; Proto-Oncogene Proteins c-sis; Treatment Outcome
PubMed: 25605424
DOI: 10.1111/jcpe.12354 -
Journal of Tissue Engineering and... Dec 2021The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in... (Meta-Analysis)
Meta-Analysis
The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in the past 20 years. Most studies reported that such agents, used in different concentrations, doses and combined with various scaffolds, might promote periodontal tissue regeneration, but evidence for the most effective combination of such agents is lacking. The objective of this study 13 was to rank the different combinations of recombinant human-derived growth and differentiation factors with/without scaffold biomaterial in the treatment of periodontal intrabony defects, through network meta-analysis of pre-clinical studies. The systematic review and network meta-analysis protocol was registered on the PROSPERO Systematic Review database with reference number: CRD42021213673. Relevant published articles were obtained after searching five electronic databases. A specific search strategy was followed by using keywords related to intrabony defects, regenerative materials, scaffolds and recombinant factors, and animal studies. All pre-clinical studies used for periodontal regeneration were included. The primary outcomes were: regeneration of junctional epithelium (mm), new cementum, connective tissue attachment, percentage of new bone formation (%), bone area (mm ), bone volume density (g/cm ) and bone height (mm) data was extracted. The analysis was carried out using network meta-analysis methods, that is illustrating network plots, contribution plots, predictive and confidence interval plot, surface under the cumulative ranking (SUCRA), multidimensional scale ranking and net funnel plots using STATA IC statistical software. An SYRCLE's tool for assessing risk of bias was used for reporting risk of bias among individual studies. A total of N = 24 for qualitative and N = 21 studies for quantitative analysis published till 2020 were included. The cumulative total number of animals included in the control and test groups were N = 162 and N = 339, respectively. The duration of the study was between 3 and 102 weeks rhBMP-2 ranked higher in SUCRA as the agent associated with the best performance for bone volume density. rhGDF-5/TCP ranked best in the bone area (mm2), rhPDGF-BB/Equine ranked best in bone height (mm), rhBMP-2 ranked best in the percentage of new bone fill, rhBMP-2/ACS ranked best in new cementum formation, and rhGDF-5/b- TCP/PLGA ranked best in connective tissue attachment and junctional epithelium. There were no adverse effects identified in the literature that could affect the different outcomes for regeneration in intrabony defects. Various recombinant factors are effective in promoting the regeneration of both soft and hard tissue supporting structures of the periodontium. However, when considering different outcomes, different agents, associated or not with biomaterials, ranked best. Keeping into account the limited transferability of results from animal studies to the clinical setting, the choice of the most appropriate formulation of bioactive agents may depend on clinical needs and purpose.
Topics: Animals; Becaplermin; Bone Morphogenetic Protein 2; Bone Regeneration; Horses; Humans; Periodontium; Recombinant Proteins; Transforming Growth Factor beta
PubMed: 34585856
DOI: 10.1002/term.3250 -
JDR Clinical and Translational Research Apr 2021The use of recombinant human platelet-derived growth factor-BB (rhPDGF) has received Food and Drug Administration approval for the treatment of periodontal and...
AIM
The use of recombinant human platelet-derived growth factor-BB (rhPDGF) has received Food and Drug Administration approval for the treatment of periodontal and orthopedic bone defects and dermal wound healing. Many studies have investigated its regenerative potential in a variety of other oral clinical indications. The aim of this systematic review was to assess the efficacy, safety, and clinical benefit of recombinant human platelet-derived growth factor (rhPDGF) use for alveolar bone and/or soft tissue regeneration.
MATERIAL AND METHODS
Comprehensive electronic and manual literature searches according to the PRISMA guidelines were performed to identify interventional and observational studies evaluating the regenerative applications of rhPDGF-BB. The primary outcomes were the safety, efficacy, and overall clinical benefit of rhPDGF use in oral regenerative procedures.
RESULTS
Sixty-three human clinical studies (mean ± SD follow-up period of 10.7 ± 3.3 mo) were included in the qualitative analysis. No serious adverse effects were reported in any of the 63 studies, aside from the postoperative complications routinely associated with surgical therapy. Use of rhPDGF was shown to be beneficial when combined with allografts, xenografts, and alloplasts (the latter tricalcium phosphate [β-TCP]) for the treatment of periodontal defects and gingival recession. The use of rhPDGF also led to favorable clinical outcomes when combined with allografts or xenografts for guided bone regeneration (GBR) and alveolar ridge preservation. While favorable clinical results support the use of the combination of rhPDGF plus allograft or xenograft for GBR, ARP, and sinus floor augmentation, current data support the use of rhPDGF and alloplasts (e.g., β-TCP) only in periodontal defects and gingival recession.
CONCLUSIONS
Based on the clinical evidence, rhPDGF is safe and provides clinical benefits when used in combination with bone allografts, xenograft, or β-TCP for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for GBR and ARP (PROSPERO CRD42020142446).
KNOWLEDGE TRANSFER STATEMENT
Clinicians should be aware that rhPDGF is a safe and effective approach for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for bone regeneration and alveolar ridge preservation. With consideration of cost and patient preference, this result could lead to more appropriate therapeutic decisions.
Topics: Alveolar Bone Loss; Becaplermin; Humans; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Sinus Floor Augmentation; United States
PubMed: 32392438
DOI: 10.1177/2380084420921353 -
BMC Health Services Research Jul 2009Tissue engineering is an emerging field. Novel bioengineered skin substitutes and genetically derived growth factors offer innovative approaches to reduce the burden of... (Review)
Review
BACKGROUND
Tissue engineering is an emerging field. Novel bioengineered skin substitutes and genetically derived growth factors offer innovative approaches to reduce the burden of diabetic foot and venous leg ulcers for both patients and health care systems. However, they frequently are very costly. Based on a systematic review of the literature, this study assesses the cost-effectiveness of these growth factors and tissue-engineered artificial skin for treating chronic wounds.
METHODS
On the basis of an extensive explorative search, an appropriate algorithm for a systematic database search was developed. The following databases were searched: BIOSIS Previews, CRD databases, Cochrane Library, EconLit, Embase, Medline, and Web of Science. Only completed and published trial- or model-based studies which contained a full economic evaluation of growth factors and bioengineered skin substitutes for the treatment of chronic wounds were included. Two reviewers independently undertook the assessment of study quality. The relevant studies were assessed by a modified version of the Consensus on Health Economic Criteria (CHEC) list and a published checklist for evaluating model-based economic evaluations.
RESULTS
Eleven health economic evaluations were included. Three biotechnology products were identified for which topical growth factors or bioengineered skin substitutes for the treatment of chronic leg ulceration were economically assessed: (1) Apligraf, a bilayered living human skin equivalent indicated for the treatment of diabetic foot and venous leg ulcers (five studies); (2) Dermagraft, a human fibroblast-derived dermal substitute, which is indicated only for use in the treatment of full-thickness diabetic foot ulcers (one study); (3) REGRANEX Gel, a human platelet-derived growth factor for the treatment of deep neuropathic diabetic foot ulcers (five studies). The studies considered in this review were of varying and partly low methodological quality. They calculated that due to shorter treatment periods, fewer complications and fewer inpatient episodes the initial cost of the novel biotechnology products may be offset, making the treatment cost-effective or even cost-saving. The results of most studies were sensitive to initial costs of the products and the evidence of effectiveness.
CONCLUSION
The study results suggest that some growth factors and tissue-engineered artificial skin products feature favourable cost-effectiveness ratios in selected patient groups with chronic wounds. Despite the limitations of the studies considered, it is evident that health care providers and coverage decision makers should take not only the high cost of the biotechnology product but the total cost of care into account when deciding about the appropriate allocation of their financial resources. However, not only the cost-effectiveness but first of all the effectiveness of these novel biotechnology products deserve further research.
Topics: Becaplermin; Collagen; Cost Savings; Cost-Benefit Analysis; Diabetic Foot; Evaluation Studies as Topic; Humans; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Skin, Artificial; Tissue Engineering; Varicose Ulcer
PubMed: 19591680
DOI: 10.1186/1472-6963-9-115