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Cancer is a severe threat to human wellness. A broad range of nanoparticles (NPs) have been developed to treat cancer. Given their safety profile, natural biomolecules such as protein-based NPs (PNPs) are promising substitutes for synthetic NPs that are currently used in drug delivery systems. In particular, PNPs have diverse characteristics and are monodisperse, chemically and genetically changeable, biodegradable, and biocompatible. To promote their application in clinical settings, PNPs must be precisely fabricated to fully exploit their advantages. This review highlights the different types of proteins that can be used to produce PNPs. Additionally, the recent applications of these nanomedicines and their therapeutic benefits against cancer are explored. Several future research directions that can facilitate the clinical application of PNPs are suggested.
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Oxidative stress and dysregulated inflammatory responses are the hallmarks of inflammatory disorders, which are key contributors to high mortality rates and impose a substantial economic burden on society. Reactive oxygen species (ROS) are vital signaling molecules that promote the development of inflammatory disorders. The existing mainstream therapeutic approaches, including steroid and non-steroidal anti-inflammatory drugs, and proinflammatory cytokine inhibitors with anti-leucocyte inhibitors, are not efficient at curing the adverse effects of severe inflammation. Moreover, they have serious side effects. Metallic nanozymes (MNZs) mimic the endogenous enzymatic process and are promising candidates for the treatment of ROS-associated inflammatory disorders. Owing to the existing level of development of these metallic nanozymes, they are efficient at scavenging excess ROS and can resolve the drawbacks of traditional therapies. This review summarizes the context of ROS during inflammation and provides an overview of recent advances in metallic nanozymes as therapeutic agents. Furthermore, the challenges associated with MNZs and an outline for future to promote the clinical translation of MNZs are discussed. Our review of this expanding multidisciplinary field will benefit the current research and clinical application of metallic-nanozyme-based ROS scavenging in inflammatory disease treatment.
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Purpose@#This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. @*Materials and Methods@#The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. @*Results@#The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. @*Conclusion@#Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.
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Purpose@#We investigated the clinical characteristics and treatment outcomes of symptomatic Meckel diverticulum (MD) in adolescents by comparison with children and adults. @*Methods@#We retrospectively reviewed the medical records of patients who underwent symptomatic MD surgery from January 2002 to December 2019. Demographic information, clinical presentations, preoperative evaluations, operative variables, postoperative outcomes, and pathologic findings were collected. We performed analyses by dividing all patients into three groups according to age at surgery: child group (<10 years), adolescent group (10–19 years), and adult group (≥20 years). @*Results@#Forty-three patients underwent symptomatic MD surgery (the child group, 14; the adolescent group, 17; and the adult group, 12). Vomiting and intestinal obstruction decreased significantly with age (P = 0.042 and 0.001), whereas hematochezia and gastrointestinal bleeding showed an increasing trend with age, although not statistically significant (P = 0.064 and 0.064). Ultrasound performance decreased significantly with age (P = 0.002), whereas CT performance showed an increasing trend with age, although not statistically significant (P = 0.193). Preoperative diagnosis rate increased significantly with age (P = 0.029). Laparoscopic surgery was performed significantly more in the adult group than in other groups (P = 0.001). The sizes of MD were significantly greater in the adolescent group than in other groups (P = 0.006 and 0.002). @*Conclusion@#The clinical characteristics and treatment outcomes of symptomatic MD in adolescents exhibit a transitional pattern between children and adults. Therefore, it is important for clinicians to recognize that adolescent patients with symptomatic MD have the characteristics of both children and adult patients to ensure optimal care.
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Background@#Chronic kidney disease (CKD) is a global health problem, and there is no permanent treatment for reversing kidney failure; thus, early diagnosis and effective treatment are required. Gene therapy has outstanding potential; however, the lack of safe gene delivery vectors, a reasonable transfection rate, and kidney targeting ability limit its application. Nanoparticles can offer innovative ways to diagnose and treat kidney diseases as they facilitate targetability and therapeutic efficacy. @*Methods@#Herein, we developed a proximal renal tubule-targeting gene delivery system based on alternative copolymer (PS) of sorbitol and polyethyleneimine (PEI), modified with vimentin-specific chitobionic acid (CA), producing PS-conjugated CA (PSC) for targeting toward vimentin-expressing cells in the kidneys. In vitro studies were used to determine cell viability, transfection efficiency, serum influence, and specific uptake in the human proximal renal tubular epithelial cell line (HK-2). Finally, the targeting efficiency of the prepared PSC gene carriers was checked in a murine model of Alport syndrome. @*Results@#Our results suggested that the prepared polyplex showed low cytotoxicity, enhanced transfection efficiency, specific uptake toward HK-2 cells, and excellent targeting efficiency toward the kidneys. @*Conclusion@#Collectively, from these results it can be inferred that the PSC can be further evaluated as a potential gene carrier for the kidney-targeted delivery of therapeutic genes for treating diseases.
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Purpose@#The study aimed to investigate the current status and prognostic factors for overall survival in patients who had undergone pulmonary metastasectomy for colorectal cancer. @*Materials and Methods@#The data of 2,573 patients who had undergone pulmonary metastasectomy after surgery for colorectal cancer between January 2009 and December 2014 were extracted from the Korean National Health Insurance Service claims database. Patient-, colorectal cancer–, pulmonary metastasis–, and hospital-related factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis to identify prognostic factors for overall survival after pulmonary metastasectomy. @*Results@#The mean age of the patients was 60.9±10.5 years; 66.2% and 79.1% of the participants were male and had distally located colorectal cancer, respectively. Wedge resection (71.7%) was the most frequent extent of pulmonary resection; 21.8% of the patients underwent repeated pulmonary metastasectomies; 73% of pulmonary metastasectomy cases were performed in tertiary hospitals; 53.9% of patients were treated in Seoul area; 82% of patients received chemotherapy in conjunction with pulmonary metastasectomy. The median survival duration was 51.8 months. The 3- and 5-year overall survival rates were 67.7% and 39.4%, respectively. In multivariate analysis, female sex, distally located colorectal cancer, pulmonary metastasectomy-only treatment, and high hospital volume (> 10 pulmonary metastasectomy cases/yr) were positive prognostic factors for survival. @*Conclusion@#Pulmonary metastasectomy seemed to provide long-term survival of patients with colorectal cancer. The female sex, presence of distally located colorectal cancer, and performance of pulmonary metastasectomy in high-volume centers were positive prognostic factors for survival.
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Objective@#This study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification. @*Materials and Methods@#Among the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed. @*Results@#The median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/ micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma. @*Conclusion@#The tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification.
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Background@#Evidence is lacking on whether the resection of lung parenchymal cancer improves the survival of patients with unexpected pleural metastasis encountered during surgery. We conducted a single-center retrospective study to determine the role of lung resection in the long-term survival of these patients. @*Methods@#Among 4683 patients who underwent lung surgery between 1995 and 2014, 132 (2.8%) had pleural metastasis. After excluding 2 patients who had incomplete medical records, 130 patients’ data were collected. Only a diagnostic pleural and/or lung biopsy was performed in 90 patients, while the lung parenchymal mass was resected in 40 patients. @*Results@#The mean follow-up duration was 29.8 months. The 5-year survival rate of the resection group (34.7%±9.4%) was superior to that of the biopsy group (15.9%±4.3%, p=0.016). Multivariate Cox regression analysis demonstrated that primary tumor resection (p=0.041), systemic treatment (p<0.001), lower clinical N stage (p=0.018), and adenocarcinoma histology (p=0.009) were significant predictors of a favorable outcome. Interestingly, primary tumor resection only played a significant prognostic role in patients who received systemic treatment. @*Conclusion@#When pleural metastasis is unexpectedly encountered during surgical exploration, resection in conjunction with systemic treatment may improve long-term survival, especially in adenocarcinoma patients without lymph node metastasis.
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Background@#Indeterminate pulmonary nodules (IPN) suspected for early stage lung cancer mandate accurate diagnosis. Both percutaneous needle biopsy (PCNB) and surgical biopsy (SB) are valuable options. The present study aimed to compare the efficacy and cost-effectiveness between PCNB and SB for IPN suspected for early stage lung cancer. @*Methods@#During January–November 2018, patients who underwent operation for IPN suspected for early stage lung cancer (SB group, n = 245) or operation after PCNB (PCNB group, n = 113) were included. Patient-level cost data were extracted from medical bills from the institution. Propensity score matching was performed between the two groups from a retrospectively-collected database. @*Results@#Fifteen patients (11.5%) had complications after PCNB; thirteen (11.5%) were not confirmed to have lung cancer through PCNB but underwent operation for IPN. In SB group, 172 (70.2%) and 7 (2.9%) patients underwent wedge resection and segmentectomy for SB, respectively; 66 patients (26.9%) underwent direct lobectomy without SB. After propensity score matching, 58 paired samples were produced. Most patients in PCNB group were admitted twice (n = 55, 94.8%). The average hospital stay was longer in PCNB group (12.9 ± 5.3 vs. 7.3 ± 3.0, P < 0.001). Though the cost of the operation was comparable (USD 12,509 ± 2,909 vs. 12,669 ± 3,334; P = 0.782), the total cost was higher for PCNB group (USD 14,403 ± 3,085 vs. 12,669 ± 3,334; P = 0.006). The average subcategory cost, which increases proportional to hospital stay, was higher in PCNB group, whereas the cost of operation and surgical materials were comparable between the two groups. @*Conclusion@#Lung cancer operation following SB for IPN was associated with lesser cost, shorter hospital stays, and lesser admission time than lung cancer operation after PCNB. The increased cost and longer hospital stay appear largely related to the admission for PCNB.
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Castleman disease is a relatively rare disease, characterized by well-circumscribed benign lymph-node hyperplasia. The disease may develop anywhere in the lymphatic system, but is most commonly reported as unicentric Castleman disease in the mediastinum along the tracheobronchial tree. It is usually asymptomatic and detected on plain chest radiography as an incidental finding. We report an incidentally detected case of Castleman disease in the paravertebral space that was preoperatively diagnosed as a neurogenic tumor and treated by complete surgical resection.
Subject(s)
Castleman Disease , Hyperplasia , Incidental Findings , Lymphatic System , Mediastinal Neoplasms , Mediastinum , Radiography , Rare Diseases , Thorax , TreesABSTRACT
BACKGROUND: Nanoparticle-mediated photothermal therapy (PTT) has been well studied as a treatment for cancer. However, the therapeutic outcome of PTT is often hindered by the penetration depth of laser light. In the tumor margin beyond the laser penetration limit, tumor recurrence often occurs, bypassing the immune response of the host. Accumulating evidence suggests the prominent role of tumor microenvironment (TME) and its interactions with the immune components contribute to an immunosuppressive milieu during the post-therapy period. Here, we explored the immunosuppressive cascade generated after PTT, which is responsible for tumor recurrence, and identified the potential targets to achieve an effective PTT period. METHODS: Here, we investigated the immunosuppressive cascade generated after PTT in a CT26 tumor bearing mouse. The liposomal system loaded with the indocyanine green (ICG) was utilized for the generation of PTT with high efficiency. Immunological factors such as cytokines and protein expressions post-therapy were investigated through enzyme-linked immunosorbent assay, flow cytometry and western blot analysis. RESULTS: Our results suggested that PTT with ICG-loaded liposomes (Lipo-ICG) was effective for the first 5 days after treatment, resulting in tumor suppression. However, an immunosuppressive and pro-inflammatory environment developed thereafter, causing the recruitment and upregulation of the immune evasion factors of heat shock protein 70, programmed death ligand 1, indoleamine-dioxygenase, interleukin-6, transforming growth factor-β, regulatory T-cells, and myeloid-derived suppressor cells, to develop immunotolerance. CONCLUSION: Collectively, these findings have determined potential therapeutic targets to modulate the TME during PTT and achieve tumor ablation without remission.
Subject(s)
Animals , Mice , Blotting, Western , Cytokines , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , HSP70 Heat-Shock Proteins , Immune Evasion , Immunologic Factors , Immunosuppression Therapy , Indocyanine Green , Interleukin-6 , Liposomes , Recurrence , T-Lymphocytes, Regulatory , Tumor Microenvironment , Up-RegulationABSTRACT
BACKGROUND: Iron oxide nanoparticles (IONPs) are excellent candidates for biomedical imaging because of unique characteristics like enhanced colloidal stability and excellent in vivo biocompatibility. Over the last decade, material scientists have developed IONPs with better imaging and enhanced optical absorbance properties by tuning their sizes, shape, phases, and surface characterizations. Since IONPs could be detected with magnetic resonance imaging, various attempts have been made to combine other imaging modalities, thereby creating a high-resolution imaging platform. Composite IONPs (CIONPs) comprising IONP cores with polymeric or inorganic coatings have recently been documented as a promising modality for therapeutic applications. METHODS: In this review, we provide an overview of the recent advances in CIONPs for multimodal imaging and focus on the therapeutic applications of CIONPs. RESULTS: CIONPs with phototherapeutics, IONP-based nanoparticles are used for theranostic application via imaging guided photothermal therapy. CONCLUSION: CIONP-based nanoparticles are known for theranostic application, longstanding effects of composite NPs in in vivo systems should also be studied. Once such issues are fixed, multifunctional CIONP-based applications can be extended for theranostics of diverse medical diseases in the future.
Subject(s)
Colloids , Iron , Magnetic Resonance Imaging , Multimodal Imaging , Nanoparticles , Optical Imaging , Polymers , Theranostic Nanomedicine , UltrasonographyABSTRACT
BACKGROUND: To explore the effect of radiation on metastatic lymph nodes (LNs) after neoadjuvant chemoradiation therapy (nCRT), we examined the metastatic features of LNs according to their inclusion in the radiation field. METHODS: The patient group included 88 men and 2 women, with a mean age of 61.1±8.1 years, who underwent esophagectomy and lymphadenectomy after nCRT. Dissected LNs were compared in terms of clinical suspicion of metastasis, nodal station, and inclusion in the radiation field. RESULTS: LN positivity did not differ between LNs that were inside (in-field [IF]) and outside (out-field [OF]) of the radiation field (IF: 40 of 465 [9%], OF: 40 of 420 [10%]; p=0.313). In clinical N+ nodal stations, IF stations had a lower incidence of metastasis than OF stations (IF/cN+: 16 of 142 [11%], OF/cN+: 9/30 [30%]; p=0.010). However, in clinical N- nodal stations, pathological positivity was not affected by whether the nodal stations were included in the radiation field (IF/cN-: 24 of 323 [7%], OF/cN-: 31 of 390 [8%]; p=0.447). CONCLUSION: Radiation therapy for nCRT could downstage clinically suspected nodal metastasis. However, such therapy was ineffective when used to treat nodes that were not suspicious for metastasis. Because significant numbers of residual metastases were identified irrespective of coverage by the radiation field, lymphadenectomy should be performed to ensure complete removal of residual nodal metastases after nCRT.
Subject(s)
Female , Humans , Male , Esophageal Neoplasms , Esophagectomy , Incidence , Lymph Node Excision , Lymph Nodes , Neoadjuvant Therapy , Neoplasm Metastasis , RadiotherapyABSTRACT
Extraskeletal osteosarcoma (ESOS) is a malignant soft tissue neoplasm producing osteoid, without any continuity with the bone or periosteum. Primary ESOS presenting in the mediastinum is an extremely rare, yet aggressive malignant tumor associated with a poor prognosis. We report a case of primary ESOS arising from the thymus in a 63-year-old male patient.
Subject(s)
Humans , Male , Middle Aged , Mediastinum , Osteosarcoma , Periosteum , Prognosis , Soft Tissue Neoplasms , Thymus GlandABSTRACT
BACKGROUND: This study investigated the clinical outcomes of surgical treatment of primary chest wall soft tissue sarcoma (CW-STS). METHODS: Thirty-one patients who underwent surgery for CW-STS between 2000 and 2015 were retrospectively reviewed. The disease-free and overall survival rates were estimated using the Kaplan-Meier method, and prognostic factors were analyzed using a Cox proportional hazards model. RESULTS: The median follow-up duration was 65.6 months. The most common histologic type of tumor was malignant fibrous histiocytoma (29%). The resection extended to the soft tissue in 14 patients, while it reached full thickness in 17 patients. Complete resection was achieved in 27 patients (87.1%). There were 5 cases of local recurrence, 3 cases of distant metastasis, and 5 cases of combined recurrence. The 5-year disease-free rate was 49%. Univariate analysis indicated that incomplete resection (p<0.001) and stage (p=0.062) were possible risk factors for recurrence. Multivariate analysis determined that incomplete resection (p=0.013) and stage (p=0.05) were significantly associated with recurrence. The overall 5- and 10-year survival rates were 86.8% and 64.3%, respectively. No prognostic factor for survival was identified. CONCLUSION: Long-term primary CW-STS surgery outcomes were found to be favorable. Incomplete microscopic resection and stage were risk factors for recurrence.
Subject(s)
Humans , Follow-Up Studies , Histiocytoma, Malignant Fibrous , Methods , Multivariate Analysis , Neoplasm Metastasis , Proportional Hazards Models , Recurrence , Retrospective Studies , Risk Factors , Sarcoma , Survival Rate , Thoracic Wall , ThoraxABSTRACT
BACKGROUND@#To explore the effect of radiation on metastatic lymph nodes (LNs) after neoadjuvant chemoradiation therapy (nCRT), we examined the metastatic features of LNs according to their inclusion in the radiation field.@*METHODS@#The patient group included 88 men and 2 women, with a mean age of 61.1±8.1 years, who underwent esophagectomy and lymphadenectomy after nCRT. Dissected LNs were compared in terms of clinical suspicion of metastasis, nodal station, and inclusion in the radiation field.@*RESULTS@#LN positivity did not differ between LNs that were inside (in-field [IF]) and outside (out-field [OF]) of the radiation field (IF: 40 of 465 [9%], OF: 40 of 420 [10%]; p=0.313). In clinical N+ nodal stations, IF stations had a lower incidence of metastasis than OF stations (IF/cN+: 16 of 142 [11%], OF/cN+: 9/30 [30%]; p=0.010). However, in clinical N- nodal stations, pathological positivity was not affected by whether the nodal stations were included in the radiation field (IF/cN-: 24 of 323 [7%], OF/cN-: 31 of 390 [8%]; p=0.447).@*CONCLUSION@#Radiation therapy for nCRT could downstage clinically suspected nodal metastasis. However, such therapy was ineffective when used to treat nodes that were not suspicious for metastasis. Because significant numbers of residual metastases were identified irrespective of coverage by the radiation field, lymphadenectomy should be performed to ensure complete removal of residual nodal metastases after nCRT.
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BACKGROUND@#This study investigated the clinical outcomes of surgical treatment of primary chest wall soft tissue sarcoma (CW-STS).@*METHODS@#Thirty-one patients who underwent surgery for CW-STS between 2000 and 2015 were retrospectively reviewed. The disease-free and overall survival rates were estimated using the Kaplan-Meier method, and prognostic factors were analyzed using a Cox proportional hazards model.@*RESULTS@#The median follow-up duration was 65.6 months. The most common histologic type of tumor was malignant fibrous histiocytoma (29%). The resection extended to the soft tissue in 14 patients, while it reached full thickness in 17 patients. Complete resection was achieved in 27 patients (87.1%). There were 5 cases of local recurrence, 3 cases of distant metastasis, and 5 cases of combined recurrence. The 5-year disease-free rate was 49%. Univariate analysis indicated that incomplete resection (p<0.001) and stage (p=0.062) were possible risk factors for recurrence. Multivariate analysis determined that incomplete resection (p=0.013) and stage (p=0.05) were significantly associated with recurrence. The overall 5- and 10-year survival rates were 86.8% and 64.3%, respectively. No prognostic factor for survival was identified.@*CONCLUSION@#Long-term primary CW-STS surgery outcomes were found to be favorable. Incomplete microscopic resection and stage were risk factors for recurrence.
ABSTRACT
Castleman disease is a relatively rare disease, characterized by well-circumscribed benign lymph-node hyperplasia. The disease may develop anywhere in the lymphatic system, but is most commonly reported as unicentric Castleman disease in the mediastinum along the tracheobronchial tree. It is usually asymptomatic and detected on plain chest radiography as an incidental finding. We report an incidentally detected case of Castleman disease in the paravertebral space that was preoperatively diagnosed as a neurogenic tumor and treated by complete surgical resection.
ABSTRACT
Extraskeletal osteosarcoma (ESOS) is a malignant soft tissue neoplasm producing osteoid, without any continuity with the bone or periosteum. Primary ESOS presenting in the mediastinum is an extremely rare, yet aggressive malignant tumor associated with a poor prognosis. We report a case of primary ESOS arising from the thymus in a 63-year-old male patient.
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BACKGROUND: Injectable biomaterials have attracted increasing attention for volume restoration and tissue regeneration. The main aim of this review is to discuss the current status of the injectable biomaterials for correction of tissue defects in plastic and reconstructive surgery. METHODS: Requirements of injectable biomaterials, mechanism of in situ gelation, characteristics, and the combinational usage of adipose-derived stem cells (ADSCs) and growth factors were reviewed. RESULTS: The ideal injectable biomaterials should be biocompatible, non-toxic, easy to use, and cost-effective. Additionally, it should possess adequate mechanical properties and stability. In situ gelation method includes physical, chemical, enzymatic and photo-initiated methods. Natural and synthetic biomaterials carry their pros and cons due to their inherent properties. The combined use of ADSCs and growth factors provides enhanced potential for adipose tissue regeneration. CONCLUSION: The usage of injectable biomaterials has been increasing for the tissue restoration and regeneration. The future of incorporating ADSCs and growth factors into the injectable biomaterials is promising.