Faculty Bibliography

PURPOSE/OBJECTIVE:The purpose of this study was to conduct a systematic review evaluating the reported complications and outcomes of bone-anchored prostheses in digit and partial hand amputees. METHODS:A literature review of primary research articles on osseointegration and bone-anchored prostheses for digit and partial amputees was performed. The Medline, Embase, Scopus, and Cochrane Library databases were queried. Inclusion criteria were journal articles that evaluated osseointegration and bone-anchored prostheses in digit and partial hand amputees. The main outcome measures were reported complications and the need for revision surgery. Secondary outcomes included all reported outcome assessments. RESULTS:Fifteen articles were included with publication dates ranging from 1996 to 2022. The sample sizes ranged from single-patient case reports to a 13-patient retrospective study. Overall, 33 men and 16 women were reported with a mean age of 33.6 years (range: 12-68) and a total of 71 amputated digits. The median follow-up was 2.1 years (IQR: 1.1-6.8 years). A total of 24 complications were reported in 14 digits (19.7%). Complications included superficial infection in 6 digits (8.5%), abutment loosening or failure in 5 (7%), fixture aseptic loosening in 4 (5.6%), deep infection in 1 (1.4%), and soft tissue instability in 1 (1.4%). Sixteen revision surgeries or component changes were reported. CONCLUSIONS:Bone-anchored prostheses using osseointegrated implants in the hand are associated with favorable outcomes in the limited number of low-quality studies available for review. Superficial infections and implant-related failures were the most frequently reported complications. TYPE OF STUDY/LEVEL OF EVIDENCE/METHODS:Systematic review IV.

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.

Blockchain technology has attracted substantial interest in recent years, most notably for its effect on global economics through the advent of cryptocurrency. Within the health care domain, blockchain technology has been actively explored as a tool for improving personal health data management, medical device security, and clinical trial management. Despite a strong demand for innovation and cutting-edge technology in plastic surgery, integration of blockchain technologies within plastic surgery is in its infancy. Recent advances and mainstream adoption of blockchain are gaining momentum and have shown significant promise for improving patient care and information management. In this article, the authors explain what defines a blockchain and discuss its history and potential applications in plastic surgery. Existing evidence suggests that blockchain can enable patient-centered data management, improve privacy, and provide additional safeguards against human error. Integration of blockchain technology into clinical practice requires further research and development to demonstrate its safety and efficacy for patients and providers.

Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing of tolerogenic dendritic cells, we identified N-myc downregulated gene 2 (Ndrg2), which marks a specific population of dendritic cell progenitors, as a promising target for CRISPR knockout. Ndrg2-knockout alters the transcriptomic profile of dendritic cells and preserves an immature cell state with a strong pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a therapeutic hydrogel for in vivo cell delivery and developed an effective translational approach for dendritic cell-based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in dendritic cells for treating various types of chronic wounds.

Although robotic surgery has been routinely established in other surgical disciplines, robotic technologies have been less readily adopted in plastic surgery. Despite a strong demand for innovation and cutting-edge technology in plastic surgery, most reconstructive procedures, including microsurgery, have continued to necessitate an open approach. Recent advances in robotics and artificial intelligence, however, are gaining momentum and have shown significant promise to improve patient care in plastic surgery. These next-generation surgical robots have the potential to enable surgeons to perform complex procedures with greater precision, flexibility, and control than previously possible with conventional techniques. Successful integration of robotic technologies into clinical practice in plastic surgery requires achieving key milestones, including implementing appropriate surgical education and garnering patient trust.

INTRODUCTION:Autologous fat grafting after breast reconstruction is a commonly used technique to address asymmetry and irregularities in breast contour. While many studies have attempted to optimize patient outcomes after fat grafting, a key postoperative protocol that lacks consensus is the optimal use of perioperative and postoperative antibiotics. Reports suggest that complication rates for fat grafting are low relative to rates after reconstruction and have been shown to not be correlated to antibiotic protocol. Studies have additionally demonstrated that the use of prolonged prophylactic antibiotics do not lower the complication rates, stressing the need for a more conservative, standardized antibiotic protocol. This study aims to identify the optimal use of perioperative and postoperative antibiotics that optimizes patient outcomes. METHODS:Patients in the Optum Clinformatics Data Mart who underwent all billable forms of breast reconstruction followed by fat grafting were identified via Current Procedural Terminology codes. Patients meeting inclusion criteria had an index reconstructive procedure at least 90 days before fat grafting. Data concerning these patient's demographics, comorbidities, breast reconstructions, perioperative and postoperative antibiotics, and outcomes were collected via querying relevant reports of Current Procedural Terminology ; International Classification of Diseases, Ninth Revision ; International Classification of Diseases, Tenth Revision ; National Drug Code Directory, and Healthcare Common Procedure Coding System codes. Antibiotics were classified by type and temporal delivery: perioperatively or postoperatively. If a patient received postoperative antibiotics, the duration of antibiotic exposure was recorded. Outcomes analysis was limited to the 90-day postoperative period. Multivariable logistic regression was performed to ascertain the effects of age, coexisting conditions, reconstruction type (autologous or implant-based), perioperative antibiotic class, postoperative antibiotic class, and postoperative antibiotic duration on the likelihood of any common postoperative complication occurring. All statistical assumptions made by logistic regression were met successfully. Odds ratios and corresponding 95% confidence intervals were calculated. RESULTS:From more than 86 million longitudinal patient records between March 2004 and June 2019, our study population included 7456 unique records of reconstruction-fat grafting pairs, with 4661 of those pairs receiving some form of prophylactic antibiotics. Age, prior radiation, and perioperative antibiotic administration were consistent independent predictors of increased all-cause complication likelihood. However, administration of perioperative antibiotics approached a statistically significant protective association against infection likelihood. No postoperative antibiotics of any duration or class conferred a protective association against infections or all-cause complications. CONCLUSIONS:This study provides national, claims-level support for antibiotic stewardship during and after fat grafting procedures. Postoperative antibiotics did not confer a protective benefit association against infection or all-cause complication likelihood, while administering perioperative antibiotics conferred a statistically significant increase in the likelihood that a patient experienced postoperative complication. However, perioperative antibiotics approach a significant protective association against postoperative infection likelihood, in line with current guidelines for infection prevention. These findings may encourage the adoption of more conservative postoperative prescription practices for clinicians who perform breast reconstruction, followed by fat grafting, reducing the nonindicated use of antibiotics.

Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential. Though different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts, it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular regeneration. The size of pores within implanted biomaterials has shown significant effects on macrophage polarization, which has been further confirmed as necessary for efficient vascular formation and remodeling. Here, we developed biodegradable, autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts' interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency rate. The synthetic vascular grafts showed similar mechanical properties to native blood vessels, encouraged macrophage populations with varying M2 to M1 phenotypic expression, and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition model. This innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.

Textured breast implants are associated with prolonged inflammation leading to increased risk for complications such as the development of anaplastic large cell lymphoma. The underlying molecular mechanisms that drive increased inflammation toward textured implants (compared with smooth implants) remain poorly understood. Here, we present the first known case of a patient with Ehlers-Danlos syndrome (EDS) who developed two independent fibrotic capsules around a single textured silicone implant. The patient was found to have one internal capsule tightly adherent to the implant and a second external capsule that was attached to the surrounding tissue. We observed that the internal implant-adherent capsule was composed of a highly aligned and dense collagen network, completely atypical for EDS and indicative of a high mechanical stress environment. In contrast, the external nonadherent capsule, which primarily interacted with the smooth surface of the internal capsule, displayed disorganized collagen fibers with no discernible alignment, classic for EDS. Remarkably, we found that the internal capsule displayed high activation of monocyte chemoattractant protein-1, a mechanoresponsive inflammatory mediator that was not elevated in the disorganized external capsule. Taken together, these findings demonstrate that the tight adhesion between the textured implant surface and the internal capsule creates a high mechanical stress environment, which is responsible for the increased local inflammation observed in the internal capsule. This unique case demonstrates that mechanical stress is able to override genetic defects locally in collagen organization and directly connects the textured surface of implants to prolonged inflammation.

Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.

BACKGROUND:Breast cancer resulting from a genetic mutations, such as BRCA1 or BRCA2, is seen in 5 to 10 percent of patients. More widespread genetic testing has increased the number of affected women undergoing prophylactic mastectomy and oophorectomy. Recent studies have yielded mixed results regarding complication rates after combined breast and ovarian operations. The authors compared surgical outcomes of breast operations performed in combination with salpingo-oophorectomies or as separate procedures. METHODS:The authors retrospectively analyzed surgical complications and length of hospital stay in 145 female patients, from which 87 had undergone combined breast surgery and salpingo-oophorectomy, and 58 had undergone these procedures separately. Multivariate logistic regression models were used to calculate odds ratios and 95 percent confidence intervals. RESULTS:Patients undergoing combined breast and ovarian operations experienced higher rates of overall complications (46.5 percent versus 19 percent; p < 0.001), infections (22.2 percent versus 8.6 percent; p < 0.05), and delayed wound healing (13.2 percent versus 0 percent; p < 0.05) related to the breast surgery, when compared with patients undergoing separate procedures. Multivariate logistic regression analysis confirmed a significant association between combined surgery and overall postoperative complications (OR, 5.87; 95 percent CI, 2.03 to 16.91; p = 0.02). Patients undergoing tissue expander-based breast reconstruction combined with ovarian surgery had significantly longer hospital stays compared to patients undergoing separate procedures (3.5 days versus 1.8 days; p < 0.001). CONCLUSIONS:The authors' data indicate that combining breast and ovarian operations is associated with a higher risk of postoperative complications related to the breast procedure and increases the duration of hospital stay in patients with tissue expander-based reconstructions. The authors' study provides valuable information for preoperative counseling of patients considering both breast and ovarian surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, III.