Scientific Abstract Presentations: Reconstructive Session 7 Sunday, October 12 Sun, Oct 12 11:00 a.m.-12:00 p.m. CDT

Purpose: Lymphedema is a progressive disorder characterized by chronic lymphatic dysfunction, fibrosis, and inflammation. Despite extensive research, the underlying cause of lymphatic vessel deterioration remains unclear. The vasa vasorum of superficial collecting lymph vessels (VCL) has been implicated in disease progression, but its role in lymphatic pathology is not well understood. This study aimed to establish a severity staging system to stratify and characterize pathophysiological changes in superficial collecting lymph vessels (SCLs) based on VCL morphology using intraoperative video-capillaroscopy (VC). Additionally, we investigated the relationship between the VCL stage and key indicators of lymphatic dysfunction, including lymphosclerosis grade, indocyanine green (ICG) lymphography stage, and endothelial cell viability assessed by D2-40 staining (podoplanin).

Methods: A retrospective review was conducted on patients with lower extremity lymphedema (LEL) who underwent intraoperative VC during lymphaticovenular anastomosis (LVA) surgery. VC images at 175× and 620× magnifications were used to classify VCL morphology into six stages (0–5) based on vessel tortuosity, branching density, luminal narrowing, and discontinuity. Histological assessment of SCLs was performed using D2-40 staining, specific marker for lymphatic endothelial cells, graded as 0 (negative), 1 (mildly positive), or 2 (strongly positive). Red blood cell (RBC) movement within the VCLs was recorded as present (score 1) or absent (score 0). Correlations between VCL stage and lymphosclerosis severity, ICG lymphography findings, and endothelial viability were statistically analyzed.

Results: One-hundred four (n=104) SCLs from 32 patients were analyzed. VCL stages were distributed as follows: stage 0 (3.8%), stage 1 (15.4%), stage 2 (17.3%), stage 3 (34.6%), stage 4 (19.2%), and stage 5 (9.6%). A higher VCL stage was significantly associated with higher lymphosclerosis grade (P=0.002) and lower D2-40 staining positivity (P<.001), indicating a loss of viable lymphatic endothelial cells. RBC movement within the VCLs decreased significantly as VCL stage progressed (P<.001), reflecting impaired perfusion. Additionally, VCL stage correlated significantly with ICG lymphography stage (P=0.007), suggesting that VCL deterioration is linked to worsening lymphatic dysfunction.

Conclusion: This study establishes a novel VCL staging system and demonstrates a strong association between VCL impairment and lymphatic vessel sclerosis, fibrosis, and endothelial dysfunction in lymphedema. Our findings suggest that chronic ischemia of the lymphatic vasa vasorum plays a central role in lymphedema progression, providing a new perspective on its pathogenesis. Since VC enables real-time assessment of microvascular changes, it could serve as a valuable tool for staging lymphedema and guiding treatment. Understanding the role of VCL pathology may also lead to the development of targeted regenerative therapies aimed at improving microvascular function and restoring lymphatic drainage in affected patients.

Purpose The presence of "linear" indocyanine green lymphography (ICGL) pattern is widely accepted as a prerequisite to successful lymphaticovenular anastomosis (LVA), with its absence considered a contraindication. However, studies have demonstrated that absence of lymphographic patterns does not equate to true anatomic absence of lymph vessels. Given the anatomic parallel between the superficial lymphatic and venous systems, we tested a "follow-the-vein" (FV) approach in performing LVA and evaluated its effectiveness in comparison to the conventional "follow-the-linear" (FL) approach.

Methods All patients who underwent LVA from January 2020 to December 2023 at Cleveland Clinic were included in the study, with the control group being those who demonstrated "linear" pattern on ICGL and the study group being those who demonstrated its absence. The surgical feasibility and outcomes were evaluated and compared with patient reported outcomes (PRO), surgical times, ICGL and volume reduction rate.

Results In our study, 98 patients underwent LVA, with 70 treated using the FL approach and 28 using the FV approach. Demographics were comparable. The FV group exhibited more severe lymphatic dysfunction, with a higher proportion of contracted (58.2%) and sclerotic (7.0%) lymphatic vessels, whereas the FL group had a greater proportion of ectatic (52.7%) and normal (12.0%) vessels. The FV group required significantly more incisions (5.11 vs. 4.56, p=0.002) and anastomoses (8.71 vs. 7.16, p=0.016). The Octopus anastomosis technique was more frequently utilized in the FV group (78.6% vs. 61.4%, p=0.166), reflecting the need for more complex reconstruction. Despite these differences, operative time (p=0.202), PRO improvements (97.1% vs. 89.3%, p=0.276), ICGL enhancement (94.3% vs. 96.4%, p=1.0), and volume reduction rate (9.7% vs. 9.2%, p=0.790) remained comparable between the two groups.

Conclusion The absence of a linear pattern in ICGL is not a contraindication for LVA. The "follow-the-vein" method provides a reliable alternative for patients without clear ICGL guidance.

1.Suami H, Taylor GI, Pan WR. The lymphatic territories of the upper limb: Anatomical study and clinical implications. Plast Reconstr Surg. 2007;119:1813-1822.

Purpose: This study aims to present the postoperative functional and quality of life (QoL) outcomes associated with using the free non-innervated latissimus dorsi (LD) muscle flap in combination with transversus abdominis release (TAR) and retrorectus mesh for reconstruction of the anterior rectus sheath in abdominal wall reconstruction (AWR) for patients with massive ventral hernias. Additionally, we sought to evaluate factors influencing patient outcomes following AWR.

Methods: This study reviewed a consecutive cohort of patients who underwent AWR with a free LD flap for massive ventral hernias, defined as hernias exceeding 15 cm in length or width or with an area greater than 150 cm². Patients were contacted at least two years postoperatively and assessed using standardized patient-reported outcome measures (PROMs), including Visual Analog Scale (VAS) for pain, Short-Form Health Survey (SF-12), Hernia-Related Quality-of-Life Survey (HerQLes), and Carolinas Comfort Scale (CCS). Data were analyzed using t-tests and linear regression models.

Results: A total of 18 patients were enrolled in the study, with a mean age of 53.0 ± 15.1 years. Of them, 13 (72.2%) and 5 (27.8%) were male and female patients, respectively. Most patients were ASA class III (n= 15, 83.3%), with 3 (16.7%) categorized as ASA class II. The mean BMI was 31.6 ± 5.1 kg/m2. Comorbidities included diabetes (27.8%), COPD (5.6%), smoking (5.6%), and immunosuppression for liver or kidney transplants (16.7%). Steroid use was noted in 11.1% of patients, and all had prior abdominal surgeries and hernia repairs. The majority of hernias (n=8; 44%) were classified as modified VHWG grade 3 or 2, while grade 1 was observed in 2 patients (11.1%). Mean hernia dimensions were 28.6±6.8 cm in length and 20.3±4.5 cm in width, with mean flap dimensions of length 26.9±2.6 cm × width 17.7±2.6 cm. The mean clinic follow-up was 8.9 months, with no flap failures or hernia recurrences. Medical complications occurred in 3 patients, and 5 patients (27.8%) experienced 8 surgical complications. Two patients died of unrelated causes. Of 16 survivors, 8 (50%) completed phone surveys at a mean follow-up of 36.8 months. In all of these patients, there was no hernia recurrence. The mean VAS, Mental Component of SF-12 (MCS-12), and Physical Component of SF-12 (PCS-12) scores were 5.5 ± 3.0, 48.3 ± 8.4, and 32.1 ± 13.9, respectively. Also, the mean HerQLes and CCS scores were 36.2 ± 33.7 and 60.7 ± 45.6, respectively. Increasing age was positively correlated with PCS-12 [0.70, P<0.05] and HerQLes scores [1.94, P<0.05] but negatively with CCS scores [-2.40, P<0.05]. Larger abdominal wall defects were associated with lower PCS-12 [-2.31, P<0.05] and HerQLes scores [-6.40, P<0.05], while CCS scores increased with defect size [8.20, P<0.05]. Higher body mass index (BMI) was linked to lower MCS-12 [-1.60, P<0.05].

Conclusions: This study shows that the free noninnervated LD flap is viable for reconstructing massive ventral hernias. Age positively impacted quality-of-life scores, while higher BMI and larger defects negatively influenced outcomes. These results highlight the complex interplay between patient characteristics and postoperative outcomes, emphasizing the importance of tailored approaches in VHR.

Background: Microsurgical breast reconstruction is intraoperatively complex, relies on multiple trained staff, requires unique techniques, and utilizes a range of specialized instruments. Prior work has highlighted that standardized workflows and process improvement approaches can improve outcomes, but the impact of staffing with consistent personnel has not been documented. We hypothesize that staffing with consistent personnel can improve clinical and operational metrics in microsurgical breast reconstruction.

Methods: All microsurgical breast reconstructions (July 2021– June 2024) at our institution were analyzed for staff familiarity at granular time-intervals (T0: setup to incision and T1-T3: each third of procedure). Staff (scrub-techs and circulators) were deemed "unfamiliar" if they worked on <2 microsurgical breast reconstructions with the attending in the past four months. In addition, average familiarity for a given staff position in a single case (denoted T_avg) was calculated by averaging familiarity for that position across all time-intervals. Intraoperative setbacks included anastomotic revisions, damage to recipient or donor vessels, switching recipient vessels, or mastectomy flap defect, and were extracted from operative notes. Major post-operative complications included operative takeback or flap loss. Staff clock-in and clock-out times, supply costs, and procedure durations were extracted from surgical logs.

Results: Among 291 surgeries across 5 attendings and 2 hospitals, 34.3% were immediate, 77.2% used standard hemiabdominal DIEP flaps, 59.1% were bilateral, and 50.0% had prior radiation. Intraoperative setbacks occurred in 19.6%, major post-operative complications in 7.2%, average duration was 628 minutes, and supply costs averaged $5,216. At the univariate level, post-operative complications were lower in first start cases (RR:0.24, p=0.03), but did not correlate with staff familiarity. Intraoperative setbacks positively correlated with unfamiliar scrub-techs (Tavg RR:1.84, p<0.05), particularly in early time-intervals (T1:1.69, p=0.06; T2:1.82, p=0.03). Unfamiliar circulators correlated with increased supply costs (Tavg +$591, p<0.05), especially in later time-intervals (T2:+$592, p<0.05; T3:+$757, p<0.05). Multivariate analysis confirmed unfamiliar scrub-techs and circulators were significantly correlated with increased intraoperative setbacks and higher costs (p<0.05), with a trend toward longer duration (p=0.06). Specifically, at the multivariate level, unfamiliar scrub-techs across the entire case (Tavg), unfamiliar circulators in T2, and prior radiation all significantly correlated with increased intraoperative setbacks (p<0.05). Unfamiliar scrub-techs and circulators in T2 and total number of anastomoses significantly correlated with increased costs (p<0.05). Bilateral reconstructions, immediate reconstructions, mastectomy type, and total number of anastomoses all significantly correlated with procedure duration (p<0.05), and unfamiliar scrub-techs in T0 approached significance of correlating with increased procedure duration (p=0.06).

Conclusion: Unfamiliar teams significantly increased intraoperative setbacks, significantly increased supply costs, and trended towards longer operative durations in microsurgical breast reconstruction cases. Furthermore, the impact of unfamiliar staff was observed at time-intervals throughout the case, from T0 through T2, and was observed at the univariate and multivariate levels. The demonstrated medical, financial, and operational benefits can be used to justify the need for consistent staffing in microsurgical breast reconstruction.

Background: Lymphedema following breast cancer surgery has a significant impact on quality of life. Immediate lymphatic reconstruction with lymphovenous bypass has shown favorable, but varied efficacy in the current literature. Thoracodorsal lymph node transfer (TDLNT) has been employed as both a pedicled and free lymph node transfer for treatment of secondary lymphedema. Here we present a novel technique and case series with early outcomes for TDLNT as a prophylactic pedicled lymph node transfer following axillary lymph node dissection for invasive breast cancer.

Methods/Technique: Patients who underwent prophylactic TDLNT were prospectively followed and a chart review was performed to obtain data regarding patient demographics, surgical characteristics, and post-operative. The primary outcome of interest was post-operative lymphedema; secondary outcomes of interest included operative complications. In terms of surgical technique, following completion of the axillary lymph node dissection by the breast surgeon, the senior plastic surgeon (KGE) performs a pedicled TDLNT. The operative area is first inspected to identify remaining vascular bundles to isolate for TDLNT. Latissimus muscle is retracted posteriorly to identify the lymphatic tissue between the serratus and latissimus muscles. The thoracoepigastric artery and vein or serratus branch of the thoracodorsal artery and vein are identified. The lymph node flap is designed to contain adipose tissue and lymph nodes centered on the proposed pedicle. The flap is then isolated, and the pedicle is raised to its origin. Lymphatic vessels going into the flap are clipped on the chest wall side to prevent lymphatic leak. SPY angiography is performed to verify perfusion throughout the flap. The flap is then transposed over the axillary vein and sutured into place.

Results: Between years 2024-2025, five patients underwent lymphatic reconstruction with pedicled TDLNT. Mean follow-up time was 123 days. All patients had a diagnosis of invasive ductal carcinoma with positive axillary nodes, and all patients were high risk for developing post-operative lymphedema. Mean number of lymph nodes removed in patients undergoing primary resection was 13.5 nodes. One of five patients had recurrent cancer limited to the breast and axilla with preoperative stage 1 lymphedema. Of these patients who underwent TDLNT, three patients did not develop post-operative lymphedema, one patient developed stage 0 post-operative lymphedema, and one patient's prior lymphedema clinically improved. One patient experienced post-operative cellulitis which was managed conservatively, and another patient experienced a minor breast wound that was managed conservatively; there were no major post-operative complications.

Conclusion: Our data suggests that TDLNT is safe and may be used prophylactically and/or therapeutically to prevent and/or treat upper extremity lymphedema following axillary dissection for invasive breast cancer. Additional data is needed to better quantify outcomes following TDLNT.

Background

Chronic obstructive pulmonary disease (COPD) is characterized by obstruction of small airways (chronic bronchitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. Such a disease process can inhibit the vital physiologic functions that are necessary to keep the lungs healthy and free of pathogens. In patients with inhalation injuries, where there can be significant airway damage, COPD patients may thus be less equipped to heal. This study examines the effect of COPD comorbidity on short-term clinical outcomes for patients with inhalation injuries.

Methods

A 12-year retrospective analysis was conducted utilizing patient records from a single tertiary care ABA-certified burn center. Cases included were inhalation injuries diagnosed via fiberoptic bronchoscopy. Outcome variables including hospital length of stay, ventilator days, and complications were compared between patients with or without a prior diagnosis of COPD.

Results

184 patients were diagnosed with inhalation injury. 69 (37.5%) had COPD. These patients were older (p<0.001) and more likely to be current smokers (p<0.001). COPD did not predict a difference in hospital days (p=0.060), ventilator days (p=0.487), nor rates of complications. Moreover, COPD did not raise the mortality rate following smoke inhalation injuries (OR=0.61, 95% CI: 0.24-1.53, p=0.297). Instead, carbon monoxide poisoning arose as the predominant risk factor of mortality (OR=3.80, 95% CI: 1.41-10.25, p=0.008). Although mortality rate was the

same regardless of COPD status, among patients who died, those with obstructive disease survived 6.0 days longer (p=0.007).

Conclusions

COPD status did not significantly impact short-term clinical outcomes in patients with house fire related inhalation injuries. Rather, the extent of cutaneous burns and systemic toxicity proved to be stronger predictors of these outcomes. Among patients who succumbed to these injuries, those with COPD had a few extra days to live. This could be due to the protective effects of COPD-related respiratory therapies, or it may simply reflect the outcomes of heightened critical care efforts in these patients.

Introduction: Burn injuries remain a significant global health burden, particularly in lower-resource settings. Understanding disparities in outcomes between low-resource and high-resource regions is needed to inform interventions. We hypothesize that burns managed in low-resource countries are an independent risk factor for mortality. Methods: We queried the World Health Organization (WHO) Global Burn Registry (GBR) from inception to September 2024. Individuals were stratified based on care in low-resource (LRC) and high-resource countries (HRC). Descriptive statistics between cohorts (LRC vs. HRC) were leveraged to summarize demographics, burn characteristics, facility resources, and hospital care outcomes. Multivariable logistic regression analysis was performed for mortality while controlling for confounding factors. Results: There were 9,274 cases with 4,169 (45%) managed in LRC and 5,105 (55%) in HRC. The median age at time of burn injury was 24 years (IQR: 4-40 years). The male population was 54% in LRC and 65% in HRC (P< 0.001). The median total body surface area (TBSA) burned was higher in LRC (20%, IQR: 10-40%) compared to HRC (15%, IQR: 5-25%, P< 0.001). Inhalation injury was also more prevalent in LRC (23%) than in HRC (9%, P< 0.001). Both the median Baux and modified Baux scores were higher for LRC, 50 and 52, respectively, compared to HRC, 41 and 42, respectively (P< 0.001). Flame injuries were significantly higher in LRC (56% vs. 43% HRC, P< 0.001). There was a significantly higher proportion of head and neck, trunk, and lower extremity burn injuries in LRC (P< 0.001). Critical care resources, computer and internet access, operating room availability, rehabilitation capabilities, and specialist capabilities were significantly lower in LRC (P< 0.001). A higher proportion of patients in HRC underwent surgery (61% vs. 40% LRC, P< 0.001). Discharge was significantly higher (82% vs. 59%) in HRC and mortality was significantly lower (11%) compared to LRC (29%, P< 0.001). After adjusting for demographics and burn-related factors, management in an LRC significantly increased the odds of mortality (OR 2.69, 95%CI 2.25-3.24, P< 0.001). Conclusions: Individuals treated in LRC had higher mortality, even after adjusting for demographic and burn injury-related characteristics. These findings underscore the need for greater access to specialized care and targeted interventions in low-resource settings to improve burn care.

Background Scalp squamous cell carcinomas (SCC) are more aggressive than SCCs in other body sites, often necessitating adjuvant radiotherapy. The effects of postoperative radiation on reconstructive outcomes remain unclear. We hypothesize that the effect of radiation on complication rates depends on reconstructive modality [i.e., free flap (FF) vs scalp flap (SF)].

Methods An IRB-approved retrospective study was performed including patients who underwent soft tissue reconstruction with a SF or FF following SCC resection from 2003-2024. Details of procedures, comorbidities, medications affecting wound healing, and postoperative radiotherapy were documented. High-risk tumors were classified as being T2b or above. Multivariable logistic regression was used to evaluate the interaction between postoperative radiation and flap type.

Results Ninety-eight patients (87.8% male; mean age: 71.8±10.5 years) were included. Common comorbidities included diabetes (39.8%) and obesity (38.8%). Immunosuppressant medications were reported in 34.7% of patients.

Eighty-five patients (85.7%) underwent solitary soft tissue reconstruction (81.2% SF, 18.8% FF). FFs and SFs were not performed at significantly different rates in patients whose tumors were recurrent (31.3% vs. 24.6%, p=0.2), demonstrated perineural invasion (56.3% vs. 20.3%, p=0.07), or were poorly differentiated (31.3% vs. 17.4%, p=0.3). Tumors were larger in the FF group (7.2±5.1cm vs 3.3±2.3cm; p<0.0001). Tumors in the FF group more often invaded deeper than fat (68.8% vs 37.7%, p=0.01). Eighty-one percent of tumors in the FF group were high-risk compared to 42.0% in the SF group (p=0.006). Radiation following reconstruction was more frequent in FFs (68.8% vs 27.5%; p=0.003). Postoperative survival was not significantly different between groups [FF: 32 months (IQR: 18-52), SF: 52 months (IQR: 25-76), p=0.2]. The proportion of patients who experienced complications was not significantly different between groups (FF: 37.5%, SF: 33.3%, p=0.75). The most common complications were partial flap loss (17.4%) and delayed wound healing (13%) in the SFs and delayed wound healing (12.5%) in FFs. In the FF group, immunosuppressed patients had higher reoperation rates (p=0.04). In the SF group, flap loss significantly increased with age (p = 0.01) and showed a marginal association with postoperative radiation (p = 0.09). Overall complication rates were higher in irradiated patients (p = 0.04). Reoperation rates were significantly higher in immunosuppressed (p=0.007) and postoperatively irradiated patients (p=0.008). The interaction between radiation and flap type was found to be significant, with increased complication risk following radiation in SFs (OR: 4.48, 95% CI: 1.50-13.4) but not FFs (95% CI: 0.03-2.32, p=0.02).

Twelve patients underwent cranioplasty and soft tissue reconstruction (4 SF, 8 FF). In SF cranioplasty patients only, hardware exposure and flap loss both increased with patient age (p=0.03, both comparisons).

Conclusions Immunosuppression was associated with increased reoperation rates for both SF and FF reconstructions. Postoperative radiation was associated with increased complications and reoperation rates in SF only. Multivariable logistic regression revealed a significant interaction between radiation and flap type on complication rate, with radiation increasing the odds of experiencing a complication following SF but not FF reconstruction. FFs may therefore be the preferred option for patients with high-risk tumors that may require adjuvant radiotherapy.

Background: Current literature suggests that lower extremity burns have higher rates of complications, graft failure, and flap failure than upper extremity and trunk injuries (1-3). There is scarce evidence analyzing the factors that contribute to graft and flap failure in these patients. Our group aims to explore the impact of affected total body surface area (TBSA), number of burn excisions, anatomical site of injury, and type of skin substitute on rates of graft and flap complications in acute burns of the lower extremity.

Methods: This retrospective cohort study analyzed all patients admitted to a single institution for treatment of acute burns of the lower extremity from 2007-2024 who underwent graft or flap based reconstruction for their injuries. Excluded patients were less than 18 years of age and those with electrical burns. Demographic data including age, sex, race/ethnicity, BMI, insurance type, and length of stay were collected. Complications, comorbidities, readmission data, and surgical details were collected. TBSA, flap and graft details, skin substitute type, and additional complications were collected via operative and postoperative reports.

Results: 98 patients met study criteria, with 284 individual grafts and 13 flaps included in analysis. Older patients were more likely to experience delayed wound healing; there were no significant changes in complication rates associated with sex, race, ethnicity, BMI, or smoking. Patients with larger TBSA% and higher number of burn excisions had no change in flap complications but had significantly increased rates of graft complications, including partial and total graft failure, delayed graft healing, and graft infection. Initial categorical analysis identified 21%-40% TBSA or greater as significantly associated with an increase in graft complications (p<0.001). Continuous variable analysis also confirmed a strong dose-response relationship, with complications rates rising proportionally with increasing TBSA% (p< 0.001). Burns affecting the foot had the lowest rate of complications, while burns affecting the buttocks had the highest rate of complications. Cadaveric-based grafts had the highest rate of graft complications, while Stratagraft, Suprathel, Primatrix, and Integra showed no significant increase in graft complications. Finally, patients with increased length of stay and any infection were more likely to experience total graft failure in multivariable models.

Conclusion: This study is the first to analyze complication rates of lower extremity grafts and flaps across a number of demographic, operative, and therapeutic strata, and further bolsters the growing rate of literature showing increased complications in lower extremity burns. Additionally, while previous studies have broadly classified lower extremity burns, this study further stratifies results by anatomical subsite, identifying site-specific risks and facilitating a more granular analysis of complication patterns. Future work should aim to extrapolate these findings to large, multicenter studies.

References: 1: Reddy S, El-Haddawi F, Fancourt M, et al. The Incidence and Risk Factors for Lower Limb Skin Graft Failure. Dermatology Research and Practice. 2014;2014:1-3. doi:https://doi.org/10.1155/2014/582080

‌2: Kasmirski JA, Alessandri-Bonetti M, Liu H, et al. Free Flap Failure and Complications in Acute Burns: A Systematic Review and Meta-analysis. Plastic and Reconstructive Surgery – Global Open. 2023;11(10):e5311. doi:https://doi.org/10.1097/GOX.0000000000005311

3: Stankiewicz M, Coyer F, Webster J, Osborne S. Incidence and Predictors of Lower Limb Split-Skin Graft Failure and Primary Closure Dehiscence in Day-Case Surgical Patients. Dermatologic Surgery. 2015;41(7):775-783. doi:https://doi.org/10.1097/dss.0000000000000391

Background/Purpose: Distraction osteogenesis (DO) is widely used for craniofacial, orthopedic, and reconstructive procedures but remains limited by prolonged healing times. Adjuncts such as stem cells, growth factors, other biological therapies have the potential to accelerate bone regeneration, yet their clinical application remains underexplored. This systematic review evaluates the efficacy of biologic adjuncts in DO and their impact on bone remodeling and healing.

Methods: A systematic review was conducted electronically through PubMed following PRISMA guidelines. The search query combined terms related to distraction osteogenesis (DO), such as "distraction osteogenesis," "mandibular distraction," "callus distraction," and "limb lengthening," with terms related to biologic adjuncts, including "biocompatible materials," "biomaterials," "stem cells," "growth factors," and "platelet-rich plasma (PRP)." Only studies in English involving human DO procedures or in vivo animal models with clear translational relevance were included. Exclusively in vitro studies, case series with fewer than five patients, and non-original research (e.g., reviews, editorials, opinion pieces) were excluded.

Results: The initial search yielded 641 publications, with 55 studies meeting inclusion criteria. Of these, 96% were preclinical experimental studies, primarily utilizing animal models (89%), while 7% included both animal and human models, and 4% were clinical studies. The clinical studies consisted of one retrospective cohort study (2%) and one randomized controlled trial (2%). Among interventions, 47% of studies evaluated stem cells, 21% biomaterial scaffolds, 15% signaling modulators, 11% growth factors (e.g., VEGF, PDGF), 11% bone morphogenetic proteins (BMPs), and 7% platelet-rich plasma (PRP). Of these, 16% investigated more than one intervention concurrently. Studies assessed multiple outcome measures, including bone regeneration (100%), callus formation (69%), consolidation time (60%), biomechanical properties (55%), and functional or patient-reported outcomes (5%). Overall, 96% of studies reported that biologic adjuncts facilitated or improved DO outcomes.

Conclusion: This systematic review highlights the extensive preclinical research on biologic adjuncts in distraction osteogenesis but reveals a critical gap in clinical validation. While 96% of studies demonstrated improved bone regeneration outcomes, nearly all were preclinical, with only 4% involving human subjects. The promising potential of stem cells, PRP, BMPs, other grown factors, and biomaterial scaffolds must be validated through well-designed clinical trials to assess their safety, efficacy, and long-term outcomes. Bridging this gap is essential to integrating biologic adjuncts into clinical practice and optimizing patient care in craniofacial and orthopedic reconstruction.