ABSTRACT
PURPOSE: To evaluate the incidence of incisional hernia in patients undergoing direct access to the abdominal cavity in urological surgery. METHODS: We conducted a systematic review in Pubmed, Embase, and Cochrane Central from 1980 to the present according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Eighty-four studies were selected for inclusion in this analysis, and meta-analysis and meta-regression were performed. RESULTS: The total incidence in the 84 studies was 4.8% (95% CI 3.7% - 6.2%) I2 93.84%. Depending on the type of incision, it was higher in the open medial approach: 7.1% (95% CI 4.3%-11.8%) I2 92.45% and lower in laparoscopic surgery: 1.9% (95% CI 1%-3.4%) I2 71, 85% According to access, it was lower in retroperitoneal: 0.9% (95% CI 0.2%-4.8%) I2 76.96% and off-midline: 4.7% (95% CI 3.5%-6.4%) I2 91.59%. Regarding the location of the hernia, parastomal hernias were more frequent: 15.1% (95% CI 9.6% - 23%) I2 77.39%. Meta-regression shows a significant effect in reducing the proportion of hernias in open lateral, laparoscopic and hand-assisted compared to medial open access. CONCLUSION: The present review finds the access through the midline and stomas as the ones with the highest incidence of incisional hernia. The use of the lateral approach or minimally invasive techniques is preferable. More prospective studies are warranted to obtain the real incidence of incisional hernias and evaluate the role of better techniques to close the abdomen.
Subject(s)
Incisional Hernia , Urologic Surgical Procedures , Humans , Incisional Hernia/epidemiology , Incisional Hernia/etiology , Incidence , Urologic Surgical Procedures/adverse effects , Laparoscopy/adverse effectsABSTRACT
BACKGROUND: Incisional hernia is a frequent complication of abdominal wall incision. Surgical technique is an important risk factor for the development of incisional hernia. The aim of these updated guidelines was to provide recommendations to decrease the incidence of incisional hernia. METHODS: A systematic literature search of MEDLINE, Embase, and Cochrane CENTRAL was performed on 22 January 2022. The Scottish Intercollegiate Guidelines Network instrument was used to evaluate systematic reviews and meta-analyses, RCTs, and cohort studies. The GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation) was used to appraise the certainty of the evidence. The guidelines group consisted of surgical specialists, a biomedical information specialist, certified guideline methodologist, and patient representative. RESULTS: Thirty-nine papers were included covering seven key questions, and weak recommendations were made for all of these. Laparoscopic surgery and non-midline incisions are suggested to be preferred when safe and feasible. In laparoscopic surgery, suturing the fascial defect of trocar sites of 10 mm and larger is advised, especially after single-incision laparoscopic surgery and at the umbilicus. For closure of an elective midline laparotomy, a continuous small-bites suturing technique with a slowly absorbable suture is suggested. Prophylactic mesh augmentation after elective midline laparotomy can be considered to reduce the risk of incisional hernia; a permanent synthetic mesh in either the onlay or retromuscular position is advised. CONCLUSION: These updated guidelines may help surgeons in selecting the optimal approach and location of abdominal wall incisions.
An incisional hernia results from a weakness of the abdominal wall muscles that allows fat from the inside or organs to bulge out. These hernias are quite common after abdominal surgery at the site of a previous incision. There is research that discusses different ways to close an incision and this may relate to the chance of hernia formation. The aim of this study was to review the latest research and to provide a guide for surgeons on how best to close incisions to decrease hernia rates. When possible, surgery through small incisions may decrease the risk of hernia formation. If small incisions are used, it may be better if they are placed away from areas that are already weak (such as the belly button). If the incision is larger than 1â cm, it should be closed with a deep muscle-fascia suture in addition to skin sutures. If there is a large incision in the middle of the abdomen, the muscle should be sutured using small stitches that are close together and a slowly absorbable suture should be used. For patients who are at higher risk of developing hernias, when closing the incision, the muscle layer can be strengthened by using a piece of (synthetic) mesh. There is no good research available on recovery after surgery and no clear guides on activity level or whether a binder will help prevent hernia formation.
Subject(s)
Abdominal Wound Closure Techniques , Incisional Hernia , Humans , Abdominal Wall/surgery , Abdominal Wound Closure Techniques/adverse effects , Incisional Hernia/epidemiology , Incisional Hernia/prevention & control , Incisional Hernia/surgery , Laparotomy , Suture Techniques , Practice Guidelines as TopicABSTRACT
BACKGROUND: The Appraisal of Guidelines Research and Evaluation (AGREE) II instrument was developed to evaluate the quality of clinical practice guidelines. Evidence suggests that development, reporting, and appraisal of guidelines on surgical interventions may be better informed by modification of the instrument. OBJECTIVE: We aimed to develop an AGREE II extension specifically designed for appraisal of guidelines of surgical interventions. METHODS: In a three-part project funded by the United European Gastroenterology and the European Association for Endoscopic Surgery, (i) we identified factors that were associated with higher quality of surgical guidelines, (ii) we statistically calibrated the AGREE II instrument in the context of surgical guidelines using correlation, reliability, and factor analysis, and (iii) we undertook a Delphi consensus process of stakeholders to inform the development of an AGREE II extension instrument for surgical interventions. RESULTS: Several features were prioritized by stakeholders as of particular importance for guidelines of surgical interventions, including development of a guideline protocol, consideration of practice variability and surgical expertise in different settings, and specification of infrastructures required to implement the recommendations. The AGREE-S-AGREE II extension instrument for surgical interventions has 25 items, compared to the 23 items of the original AGREE II instrument, organized into the following 6 domains: Scope and purpose, Stakeholders, Evidence synthesis, Development of recommendations, Editorial independence, and Implementation and update. As the original instrument, it concludes with an overall appraisal of the quality of the guideline and a judgement on whether the guideline is recommended for use. Several items were amended and rearranged among domains, and an item was deleted. The Rigor of Development domain of the original AGREE II was divided into Evidence Synthesis and Development of Recommendations. Items of the AGREE II domain Clarity of Presentation were incorporated in the new domain Development of Recommendations. Three new items were introduced, addressing the development of a guideline protocol, support by a guideline methodologist, and consideration of surgical experience/expertise. CONCLUSION: The AGREE-S appraisal instrument has been developed to be used for assessment of the methodological and reporting quality of guidelines on surgical interventions.
Subject(s)
Reproducibility of Results , Consensus , HumansABSTRACT
BACKGROUND: Over the past 25 years, the European Association for Endoscopic Surgery (EAES) has been issuing clinical guidance documents to aid surgical practice. We aimed to investigate the awareness and use of such documents among EAES members. Additionally, we conceptually appraised the methodology used in their development in order to propose a bundle of actions for quality improvement and increased penetration of clinical practice guidelines among EAES members. METHODS: We invited members of EAES to participate in a web-based survey on awareness and use of these documents. Post hoc analyses were performed to identify factors associated with poor awareness/use and the reported reasons for limited use. We further summarized and conceptually analyzed key methodological features of clinical guidance documents published by EAES. RESULTS: Three distinct consecutive phases of methodological evolvement of clinical guidance documents were evident: a "consensus phase," a "guideline phase," and a "transitional phase". Out of a total of 254 surgeons who completed the survey, 72% percent were aware of EAES guidelines and 47% reported occasional use. Young age and trainee status were associated with poor awareness and use. Restriction by colleagues was the primary reason for limited use in these subgroups. CONCLUSIONS: The methodology of EAES clinical guidance documents is evolving. Awareness among EAES members is fair, but use is limited. Dissemination actions should be directed to junior surgeons and trainees.
Subject(s)
Endoscopy/methods , Adult , Consensus , Evaluation Studies as Topic , Humans , Middle Aged , Surveys and QuestionnairesABSTRACT
OBJECTIVE: To inform the development of an AGREE II extension specifically tailored for surgical guidelines. AGREE II was designed to inform the development, reporting, and appraisal of clinical practice guidelines. Previous research has suggested substantial room for improvement of the quality of surgical guidelines. METHODS: A previously published search in MEDLINE for clinical practice guidelines published by surgical scientific organizations with an international scope between 2008 and 2017, resulted in a total of 67 guidelines. The quality of these guidelines was assessed using AGREE II. We performed a series of statistical analyses (reliability, correlation and Factor Analysis, Item Response Theory) with the objective to calibrate AGREE II for use specifically in surgical guidelines. RESULTS: Reliability/correlation/factor analysis and Item Response Theory produced similar results and suggested that a structure of 5 domains, instead of 6 domains of the original instrument, might be more appropriate. Furthermore, exclusion and re-arrangement of items to other domains was found to increase the reliability of AGREE II when applied in surgical guidelines. CONCLUSIONS: The findings of this study suggest that statistical calibration of AGREE II might improve the development, reporting, and appraisal of surgical guidelines.
Subject(s)
Research Design , Calibration , Factor Analysis, Statistical , Humans , Reproducibility of ResultsABSTRACT
OBJECTIVE: The aim of the study was to identify clinical practice guidelines published by surgical scientific organizations, assess their quality, and investigate the association between defined factors and quality. The ultimate objective was to develop a framework to improve the quality of surgical guidelines. SUMMARY BACKGROUND DATA: Evidence on the quality of surgical guidelines is lacking. METHODS: We searched MEDLINE for clinical practice guidelines published by surgical scientific organizations with an international scope between 2008 and 2017. We investigated the association between the following factors and guideline quality, as assessed using the AGREE II instrument: number of guidelines published within the study period by a scientific organization, the presence of a guidelines committee, applying the GRADE methodology, consensus project design, and the presence of intersociety collaboration. RESULTS: Ten surgical scientific organizations developed 67 guidelines over the study period. The median overall score using AGREE II tool was 4 out of a maximum of 7, whereas 27 (40%) guidelines were not considered suitable for use. Guidelines produced by a scientific organization with an output of ≥9 guidelines over the study period [odds ratio (OR) 3.79, 95% confidence interval (CI), 1.01-12.66, P = 0.048], the presence of a guidelines committee (OR 4.15, 95% CI, 1.47-11.77, P = 0.007), and applying the GRADE methodology (OR 8.17, 95% CI, 2.54-26.29, P < 0.0001) were associated with higher odds of being recommended for use. CONCLUSIONS: Development by a guidelines committee, routine guideline output, and adhering to the GRADE methodology were found to be associated with higher guideline quality in the field of surgery.
Subject(s)
Practice Guidelines as Topic/standards , Quality Improvement , Surgical Procedures, Operative/standards , Humans , Internationality , Organizations , PublishingABSTRACT
BACKGROUND: Systematic reviews play a crucial role in clinical decision making and resource allocation and are expected to be unbiased and consistent. The aim of this study is a review of systematic reviews on the use of prophylactic mesh to prevent parastomal hernia (PH) formation using ROBIS and AMSTAR tools to assess the risk of bias and methodological quality. METHODS: We included systematic reviews with or without meta-analysis of which the objective was to assess the use of a prophylactic mesh to prevent PH. A systematic search of the literature in five databases from inception until December 2017 was conducted. For each systematic review, methodologic quality and risk of bias were assessed using the AMSTAR and ROBIS tools, respectively. We estimated the inter-rater reliability for individual domains and for the overall methodological quality and risk of bias using Fleiss' k. RESULTS: We identified 14 systematic reviews that met the inclusion criteria. Using the AMSTAR scale with a cutoff value, six reviews showed high methodologic quality and eight were of low quality. Using the ROBIS tool, the overall risk of bias was low in 50% of the reviews analyzed. In the remaining studies, the risk of bias was unclear. CONCLUSIONS: The global evidence in favor of the use of a prophylactic mesh for preventing PH is not uniform regarding quality and risk of bias. Surgeons cannot be equally confident in the results of all systematic reviews published on this topic.
Subject(s)
Hernia, Abdominal/prevention & control , Incisional Hernia/prevention & control , Review Literature as Topic , Surgical Mesh , Bias , Colostomy/adverse effects , Hernia, Abdominal/etiology , Humans , Incisional Hernia/etiology , Meta-Analysis as Topic , Reproducibility of ResultsABSTRACT
BACKGROUND: Povidone iodine (PVI) is a widely used antiseptic solution among surgeons. A meta-analysis based on randomized controlled trials (RCTs) was conducted to establish whether application of PVI before wound closure could reduce surgical site infection (SSI) rates. METHODS: Systematic review of MEDLINE/PubMed, Scopus, CINAHL, and Web of Science databases from inception to September 2017, with no language restrictions. Only RCTs were retrieved. The primary outcome was the SSI rate. Meta-analysis was complemented with trial sequential analysis (TSA). RESULTS: A total of 7601 patients collected from 16 RCTs were analyzed. A reduction in overall SSI rate was found (RR 0.64, 95% CI 0.48-0.85, P = 0.002, I2 = 65%), which was attributed to patients undergoing elective operations (n = 2358) and mixed elective/urgent operations (n = 2019). When RCTs of uncertain quality (n = 9) were excluded, the use of PVI before wound closure (n = 4322 patients) was not associated with a significant reduction of SSI (RR 0.81, 95% CI 0.55-1.20, P = 0.29, I2 = 51%) and was only significant in clean wounds (RR 0.25, 95% CI 0.09-0.70, P = 0.008, I2 = 0%). For the primary outcome, the TSA calculation using a relative risk reduction of 19% and an 11% proportion of control event rate (CER) with 51% of I2, the accrued information size (n = 4322) was 32.8% of the estimated optimal information size (n = 13,148). CONCLUSIONS: There is no conclusive evidence for a strong recommendation of topical PVI before wound closure to prevent SSI.
Subject(s)
Anti-Infective Agents, Local/administration & dosage , Povidone-Iodine/administration & dosage , Surgical Wound Infection/prevention & control , Administration, Topical , Humans , Iodine , Wound HealingABSTRACT
OBJECTIVE: Incisional hernia (IH) after colorectal surgery is highly prevalent. The objective of this study is to assess the utility of an algorithm to decide on mesh augmentation after a midline laparotomy for colorectal resection to prevent IH in high-risk patients. METHODS: A prospective study was conducted including all patients undergoing a midline laparotomy for colorectal resection between January 2011 and June 2014, after the implementation of a decision algorithm for prophylactic mesh augmentation in selected high-risk patients. Intention-to-treat analyses were conducted between patients in which the algorithm was correctly applied and those in which it was not. RESULTS: From the 235 patients analysed, the algorithm was followed in 166 patients, the resting 69 cases were used as a control group. From an initial adherence to the algorithm of 40% in the first semester, a 90.3% adherence was achieved in the seventh semester. The incidence of IH decreased as the adherence to the algorithm increased (from 28 to 0%) with a time-related correlation (R2=0.781). A statistically significant reduction in IH incidence was demonstrated in high-risk groups in which the algorithm was correctly applied (10,2 vs. 46,3%; p=0,0001; OR: 7,58;95%; CI: 3,8-15). Survival analysis showed that the differences remained constant during follow-up. CONCLUSION: The implementation of the algorithm reduces the incidence of IH in high-risk patients. The adherence to the algorithm also correlates with a decrease in the incidence of IH.
Subject(s)
Algorithms , Colorectal Neoplasms/surgery , Incisional Hernia/prevention & control , Laparotomy , Surgical Mesh , Aged , Decision Support Systems, Clinical , Female , Humans , Incidence , Incisional Hernia/epidemiology , Male , Prospective Studies , Risk AssessmentABSTRACT
OBJECTIVE: The aim of this study was to assess the reduction in the incidence of parastomal hernia (PH) after placement of prophylactic synthetic mesh using a modified Sugarbaker technique when a permanent end-colostomy is needed. SUMMARY OF BACKGROUND DATA: Prevention of PH formation is crucial given the high prevalence of PH and difficulties in the surgical repair of PH. METHODS: A randomized, prospective, double-blind, and controlled trial. Rectal cancer patients undergoing laparoscopic abdominoperineal resection with permanent colostomy were randomized (1â:â1) to the mesh and nonmesh arms. In the mesh group, a large-pore lightweight composite mesh was placed in the intraperitoneal/onlay fashion using a modified Sugarbaker technique. PH was detected by computed tomography (CT) after a minimum follow-up of 12 months. Analysis was per-protocol. RESULTS: The mesh group included 24 patients and the control group 28. Preoperative data, surgical time, and postoperative morbidity were similar. The median follow-up was 26 months. After CT examination, 6 of 24 PHs (25%) were observed in the mesh group compared with 18 of 28 (64.3%) in the nonmesh group (odds ratio 0.39, 95% confidence interval 0.18-0.82; P = 0.005). The Kaplan-Meier curves showed significant differences in favor of the mesh group (long-rank = 4.21, P = 0.04). The number needed to treat was 2.5, which confirmed the effectiveness of the intervention. CONCLUSIONS: Placement of a prosthetic mesh by the laparoscopic approach following the modified Sugarbaker technique is safe and effective in the prevention of PH, reducing significantly the incidence of PH.
Subject(s)
Abdominal Wall/surgery , Colostomy , Hernia, Ventral/prevention & control , Postoperative Complications/prevention & control , Rectal Neoplasms/surgery , Surgical Mesh , Aged , Double-Blind Method , Female , Humans , Laparoscopy/methods , Male , Postoperative Complications/mortality , Prospective Studies , Rectal Neoplasms/mortality , Spain , Treatment OutcomeABSTRACT
INTRODUCTION: The aim of this study was to the data from the National Registry of Incisional Hernia (EVEREG) to determine the reality of the treatment of this condition in Spain. METHODS: EVEREG is an online prospective database which has been functioning since July 2012; operations for incisional hernia are anonymously recorded. RESULTS: Up to March 2015, 4501 hernias from 95 of the 113 participating hospitals were registered. The mean age of the patients was 62.7, and 56.5% were women, with a mean BMI of 30.2kg/m2; 29.8% presented a high surgical risk (ASA III-V). A total of 93.7% were scheduled surgeries, 88.3% open surgery and 22.2% were recurrent incisional hernias. There were 66.9% hernias after a midline laparotomy, and 81.4% of a transverse diameter of less than 10cm. A mesh was used in 96.2% of cases. Postoperative stay was 5.3 days and 29.1% presented a complication, with a mortality of 0.8%. After a median follow-up of 7.7 months a high rate of recurrence was detected (20.7% per year), especially in hernias that were operated on after a previous repair (18.1% primary vs. 30.6% recurrent; P=.004). CONCLUSION: the EVEREG registry is a useful tool to know the current situation of incisional hernia treatment. Analysis of the data shows several points that could be improved: a low rate of follow-up and high recurrence rate.
Subject(s)
Databases, Factual , Incisional Hernia/surgery , Registries , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , SpainABSTRACT
The closure of a temporary stoma involves 2 different surgical procedures: the stoma reversal procedure and the abdominal wall reconstruction of the stoma site. The management of the abdominal wall has different areas that should be analyzed such us how to avoid surgical site infection (SSI), the technique to be used in case of a concomitant hernia at the stoma site or to prevent an incisional hernia in the future, how to deal with the incision when the stoma reversal procedure is performed by laparoscopy and how to close the skin at the stoma site. The aim of this paper is to analyze these aspects in relation to abdominal wall reconstruction during a stoma reversal procedure.
Subject(s)
Abdominal Wound Closure Techniques , Surgical Stomas , HumansABSTRACT
BACKGROUND: Previous randomized clinical trials, systematic reviews, and meta-analyses evaluating parastomal hernia prevention with mesh placement during end colostomy formation have reported contradictory results. This review aimed to assess the efficacy of this strategy in long-term follow-up according to the latest available data. METHODS: Medline, EMBASE, Cochrane Library, Web of Science, and Google Scholar were searched. Randomized clinical trials were included if they compared mesh with no mesh during initial end colostomy creation in adult patients to prevent parastomal hernia with a follow-up longer than 2 years. A meta-analysis was performed to evaluate parastomal hernia incidence (primary outcome), parastomal hernia repair rate, and mortality. Subgroup analysis included surgical approach and mesh position, and trial sequential analysis was performed. RESULTS: Eight randomized clinical trials involving 537 patients met the inclusion criteria. Based on long-term follow-up, the incidence of parastomal hernia was not reduced when a prophylactic mesh was placed (relative risk = 0.68 [95% confidence interval:0.46-1.02]; I2 = 81%, P =.06). The parastomal hernia repair rate was low; however, no difference was found between the groups (relative risk = 0.90 [95% confidence interval:0.51-1.56]; I2 = 0%; P = .70), and no difference was detected between the groups when mortality was assessed (relative risk = 1.03 [95% confidence interval: 0.77-1.39]; I2 = 21%; P = .83). Subgroup analyses did not show differences according to the surgical approach or mesh position used. Regarding trial sequential analysis, an optimal information size was not achieved. CONCLUSION: Prophylactic mesh placement during end colostomy formation does not prevent parastomal hernia in the long term. The parastomal hernia repair rate and mortality rate did not vary between the included groups. Heterogeneity among the included randomized clinical trials might restrict the reliability of the results.
Subject(s)
Incisional Hernia , Surgical Stomas , Humans , Colostomy/adverse effects , Incidence , Incisional Hernia/epidemiology , Incisional Hernia/etiology , Incisional Hernia/prevention & control , Reproducibility of Results , Surgical Mesh , Surgical Stomas/adverse effects , Randomized Controlled Trials as TopicABSTRACT
The Spanish Association of Surgeons (AEC) deems it essential to define and regulate the acquisition of high-specialization competencies within General Surgery and Gastrointestinal Surgery and proposes the Regulation for the accreditation of specialized surgical units. The AEC aims to define specialized surgical units as those functional elements of the health system that meet the defined requirements regarding their provision, solvency, and specialization in care, teaching, and research. In this paper we present the proposed accreditation model for Abdominal Wall Surgery Units, as well as the results of a survey conducted to assess the status of such units in our country. The model presented represents one of the pioneering initiatives worldwide concerning the accreditation of Abdominal Wall Surgery Units.
Subject(s)
Abdominal Wall , Accreditation , Accreditation/standards , Spain , Humans , Abdominal Wall/surgery , Specialties, Surgical/standards , Hospital Units/organization & administration , Hospital Units/standardsABSTRACT
Analyses of registries and medical imaging suggest that laparoscopic surgery may be penalized with a high incidence of trocar-site hernias (TSH). In addition to trocar diameter, the location of the surgical wound (SW) may affect TSH incidence. The intra-abdominal pressure (IAP) exerted on the abdominal wall (AW) might also influence the appearance of TSH. In the present study, we used finite element (FE) simulations to predict the influence of trocar location and SW characteristics (stiffness) on the mechanical behavior of the AW subject to an IAP. Two models of laparoscopy patterns on the AW, with trocars in the 5-12 mm range, were generated. FE simulations for IAP values within the 4 kPa-20 kPa range were carried out using the Code Aster open-source software. Different stiffness levels of the SW tissue were considered. We found that midline-located surgical wounds barely deformed, even though they moved outwards along with the regular LA tissue. Laterally located SWs hardly changed their location but they experienced significant variations in their volume and shape. The amount of deformation of lateral SWs was found to strongly depend on their stiffness. Trocar incisions placed in a LA with non-diastatic dimensions do not compromise its mechanical integrity. The more lateral the trocars are placed, the greater is their deformation, regardless of their size. Thus, to prevent TSH it might be advisable to close lateral trocars with a suture, or even use a prosthetic reinforcement depending on the patient's risk factors (e.g., obesity).
Subject(s)
Abdominal Wall , Laparoscopy , Humans , Abdominal Wall/surgery , Biomechanical Phenomena , Cicatrix/etiology , Laparoscopy/adverse effects , Surgical Instruments/adverse effects , ThyrotropinABSTRACT
Soft tissue defects, such as incisional hernia or pelvic organ prolapse, are prevalent pathologies characterized by a tissue microenvironment rich in fragile and dysfunctional fibroblasts. Precision medicine could improve their surgical repair, currently based on polymeric materials. Nonetheless, biomaterial-triggered interventions need first a better understanding of the cell-material interfaces that truly consider the patients' biology. Few tools are available to study the interactions between polymers and dysfunctional soft tissue cells in vitro. Here, we propose polypropylene (PP) as a matrix to create microscale surfaces w/wo functionalization with an HBII-RGD molecule, a fibronectin fragment modified to include an RGD sequence for promoting cell attachment and differentiation. Metal mold surfaces were roughened by shot blasting with aluminum oxide, and polypropylene plates were obtained by injection molding. HBII-RGD was covalently attached by silanization. As a proof of concept, primary abdominal and vaginal wall fasciae fibroblasts from control patients were grown on the new surfaces. Tissue-specific significant differences in cell morphology, early adhesion and cytoskeletal structure were observed. Roughness and biofunctionalization parameters exerted unique and combinatorial effects that need further investigation. We conclude that the proposed model is effective and provides a new framework to inform the design of smart materials for the treatment of clinically compromised tissues.