Regulating Tissue Growth Factors for Healing with Etherified Carboxymethylcellulose Matrix.

Etherified Carboxymethylcellulose Matrix (eCMC) is a revolutionary application of carboxymethylcellulose (CMC) in wound care, known for its potential in hemostasis and tissue regeneration. This study aims to investigate the mechanism of eCMC in tissue healing by establishing a rat burn model and administering eCMC as a treatment. The objective is to analyze cytokines and inflammatory mediators using a Cytokine Array and histochemical staining to understand the effects of eCMC on tissue regeneration. A rat burn model was created, and eCMC was applied as a treatment. Tissue samples were collected at multiple time points to assess the expression of cytokines and inflammatory mediators using a Cytokine Array. Additionally, histochemical staining was performed to evaluate tissue regeneration factors. eCMC induced the expression of endogenous cytokines, particularly VEGF and PDGF, while inhibiting inflammatory cytokines such as CINC-1, CINC-2, and MMP-8. This dual action facilitated wound healing and mitigated the risk of infection. eCMC demonstrates promising potential for enhancing skin regeneration. Further research is warranted to delve into the precise mechanism of eCMC's cytokine regulation. In vitro and in vivo studies should be conducted to comprehensively investigate the therapeutic capabilities of eCMC in wound healing.

Urine-derived stem cells genetically modified with IGF1 improve muscle regeneration.

OBJECTIVE: In this study we aimed to determine the impact of human urine derived stem cells (USC) and genetically modified USC that were designed to overexpress myogenic growth factor IGF1 (USCIGF), on the regenerative capacity of cardiotoxin (CTX)-injured murine skeletal muscle. METHODS: We overexpressed IGF1 in USC and investigated the alterations in myogenic capacity and regenerative function in cardiotoxin-injured muscle tissues. RESULTS: Compared with USC alone, USCIGF1 activated the IGF1-Akt-mTOR signaling pathway, significantly improved myogenic differentiation capacity in vitro, and enhanced the secretion of myogenic growth factors and cytokines. In addition, IGF1 overexpression increased the ability of USC to fuse with skeletal myocytes to form myotubes, regulated the pro-regenerative immune response and inflammatory cytokines, and increased myogenesis in an in vivo model of skeletal muscle injury. CONCLUSION: Overall, USC genetically modified to overexpress IGF1 significantly enhanced skeletal muscle regeneration by regulating myogenic differentiation, paracrine effects, and cell fusion, as well as by modulating immune responses in injured skeletal muscles in vivo. This study provides a novel perspective for evaluating the myogenic function of USC as a nonmyogenic cell source in skeletal myogenesis. The combination of USC and IGF1 expression has the potential to provide a novel efficient therapy for skeletal muscle injury and associated muscular defects in patients with urinary incontinence.

Age-Related Changes in Urethral Structure and Responds to Injury: Single-Cell Atlas of a Rat Model of Vaginal Birth Injury induced Stress Urinary Incontinence.

Stress urinary incontinence (SUI) greatly affects the daily life of numerous women and is closely related to a history of vaginal delivery and aging. We used vaginal balloon dilation to simulate vaginal birth injury in young and middle-aged rats to produce a SUI animal model, and found that young rats restored urethral structure and function well, but not the middle-aged rats. To identify the characteristics of cellular and molecular changes in the urethral microenvironment during the repair process of SUI. We profiled 51,690 individual female rat urethra cells from 24 and 48 weeks old, with or without simulated vaginal birth injury. Cell interaction analysis showed that signal networks during repair process changed from resting to active, and aging altered the distribution but not the overall level of cell interaction in the repair process. Similarity analysis showed that muscle, fibroblasts, and immune cells underwent large transcriptional changes during aging and repair. In middle-aged rats, cell senescence occurs mainly in the superficial and middle urothelium due to cellular death and shedding, and the basal urothelium expressed many Senescence-Associated Secretory Phenotype (SASP) genes. In conclusion, we established the aging and vaginal balloon dilation (VBD) model of female urethral cell anatomy and the signal network landscape, which provides an insight into the normal or disordered urethra repair process and the scientific basis for developing novel SUI therapies.

Neurobiological insights into lower urinary tract dysfunction: evaluating the role of brain-derived neurotrophic factor.

Lower urinary tract dysfunction (LUTD) encompasses a range of debilitating conditions that affect both sexes and different age groups. Understanding the underlying neurobiological mechanisms contributing to LUTD has emerged as a critical avenue for the development of targeted therapeutic strategies. Brain-derived neurotrophic factor (BDNF), a prominent member of the neurotrophin family, has attracted attention due to its multiple roles in neural development, plasticity, and maintenance. This review examines the intricate interplay between neurobiological factors and LUTD, focusing on the central involvement of BDNF. The review emphasizes the bidirectional relationship between LUTD and BDNF and explores how LUTD-induced neural changes may affect BDNF dynamics and vice versa. Growth factor therapy and the combined administration of controlled release growth factors and stem cells are minimally invasive treatment strategies for neuromuscular injury. Among the many growth factors and cytokines, brain-derived neurotrophic factor (BDNF) plays a prominent role in neuromuscular repair. As an essential neurotrophin, BDNF is involved in the modulation of neuromuscular regeneration through tropomyosin receptor kinase B (TrkB). Increasing BDNF levels facilitates the regeneration of the external urethral sphincter and contributes to the regulation of bladder contraction. Treatments targeting the BDNF pathway and sustained release of BDNF may become novel treatment options for urinary incontinence and other forms of lower urinary tract dysfunction. This review discusses the applications of BDNF and the theoretical basis for its use in the treatment of lower urinary tract dysfunction, including urinary incontinence (UI), overactive bladder (OAB), and benign prostatic hyperplasia (BPH), and in the clinical diagnosis of bladder dysfunction.

A prospective study of the prostate health index density and multiparametric magnetic resonance imaging in diagnosing clinically significant prostate cancer.

PURPOSE: To evaluate the predictive performance of the prostate health index (PHI) and PHI density (PHID), for clinically significant prostate cancer (csPCa) in patients with a PI-RADS score ≤3. MATERIALS AND METHODS: Patients tested for total prostate-specific antigen (tPSA, ≤100 ng/mL), free PSA (fPSA), and p2PSA at Peking University First Hospital were prospectively enrolled. Possible predictive factors of csPCa were analyzed using the receiver operating characteristic (ROC) curve. Results were expressed as area under the curve (AUC) with 95% confidence intervals (CI). The cutoff values of PHI and PHID were determined. RESULTS: We enrolled 222 patients in this study. The prevalence of csPCa in the PI-RADS ≤3 subgroup (n=89) was 22.47% (20/89). Age, tPSA, F/T, prostate volume, PSA density, PHI, PHID, and PI-RADS score were significantly associated with csPCa. PHID (AUC: 0.829 [95% CI: 0.717-0.941]) was the best predictor of csPCa. PHID >0.956 was set as the threshold of suspicious csPCa with a sensitivity of 85.00% and a specificity of 73.91%, avoiding 94.44% of unnecessary biopsies but missing 15.00% csPCa. A threshold of PHI ≥52.83 showed the same sensitivity but a rather lower specificity of 65.22% that avoided 93.75% of unnecessary biopsies. CONCLUSIONS: PHI and PHID have the best predictive performance of csPCa in patients with PI-RADS score ≤3. A threshold value of PHID ≥0.956 may be used as the criterion for biopsy in these patients.

Recent advances in stem cell therapy for erectile dysfunction: a narrative review.

INTRODUCTION: While phosphodiesterase type 5 inhibitors (PDE5is) and others are used to treat Erectile dysfunction (ED), many patients are either unresponsive or resistant to it. Stem cell therapy (SCT) is a promising alternative approach. Numerous preclinical trials have demonstrated improved erectile function in animal models using SCT, although the number of clinical trials investigating SCT for men with ED is limited. Nonetheless, findings from human clinical trials suggest that SCT may be a useful treatment option. AREAS COVERED: Biomedical literature, including PubMed, ClinicalTrials.gov, and European Union Clinical Trials Registry, were analyzed to summarize and synthesize information on stem cell therapy for ED in this narrative review. The achievements in preclinical and clinical evaluations are presented and critically analyzed. EXPERT OPINION: SCT has demonstrated some benefits in improving erectile function, while further studies are urgently needed. Such studies would provide valuable insights into the optimal use of stem cell therapy and its potential as a therapeutic option for ED. Taking advantage of different mechanisms of action involved in various regenerative therapies, combination therapies such as SCT and low-energy shock waves or platelet-rich plasma may provide a more effective therapy and warrant further research.

Effect of near-infrared laser treatment on improving erectile function in rats with diabetes mellitus.

BACKGROUND: Diabetes mellitus-induced erectile dysfunction is difficult to treat. The oxidative stress created by diabetes mellitus is a major cause of injuries to the corpus cavernosum, thereby resulting in erectile dysfunction. Near-infrared laser has already been shown to be effective in treating multiple brain disorders because of its antioxidative stress effect. OBJECTIVES: To investigate whether a near-infrared laser improves the erectile function of diabetes mellitus-induced erectile dysfunction rats through its antioxidative stress effect. MATERIALS AND METHODS: Knowing its advantage of reasonable deep tissue penetration and good photoactivation on mitochondria, a near-infrared laser with wavelength of 808 nm was used in the experiment. Since the internal and external corpus cavernosum were covered by different tissue layers, the laser penetration rates of the internal and external corpus cavernosum were measured separately. Different radiant exposure settings were applied: in the initial experiment, 40 male Sprague-Dawley rats were randomly assigned to five groups, normal controls, and streptozotocin-induced diabetes mellitus rats that 10 weeks later received various radiant exposures (J/cm2 ) from the near-infrared laser (DM0J(DM+NIR 0 J/cm2 ), DM1J, DM2J, and DM4J) in the subsequent 2 weeks. Erectile function was then assessed 1 week after near-infrared treatment. It was found that the initial radiant exposure setting was not optimal according to the Arndt-Schulz rule. We performed a second experiment using a different radiant exposure setting. Forty male rats were randomly divided into five groups (normal controls, DM0J, DM4J, DM8J, and DM16J), and the near-infrared laser was again applied according to the new setting, and erectile function was assessed as in the first experiment. Histologic, biochemical, and proteomic analyses were then conducted. RESULTS: Recovery of erectile function of varying degrees was observed in the near-infrared treatment groups, and radiant exposure of 4 J/cm2 achieved optimal results. The DM4J group showed improvement in mitochondrial function and morphology in diabetes mellitus rats, and it was found that oxidative stress levels were significantly reduced by near-infrared exposure. The tissue structure of the corpus cavernosum was also improved by near-infrared exposure. The proteomics analysis confirming multiple biologic processes were changed by diabetes mellitus and near-infrared. DISCUSSION AND CONCLUSION: Near-infrared laser activated mitochondria, improved oxidative stress, repaired the damage to penile corpus cavernosum tissue structures caused by diabetes mellitus, and improved erectile function in diabetes mellitus rats. These results thus raise the possibility that human patients with diabetes mellitus-induced erectile dysfunction may respond to near-infrared therapy in a manner that parallels the responses we observed in animal study.

Molecular Mechanism of Action of Low-Intensity Extracorporeal Shockwave Therapy for Regenerating Penile and Peripheral Nerves.

Sufficient functional repair of damaged peripheral nerves is a big clinical challenge in terms of long-lasting morbidity, disability, and economic costs. Nerve damage after radical prostatectomy is the most common cause of erectile dysfunction. In recent years, low-intensity extracorporeal shockwave therapy has been explored to improve the outcomes of peripheral nerve repair and regeneration. Research indicated that application of low-intensity extracorporeal shockwave therapy after nerve surgery promoted nerve regeneration and improved the functional outcomes, underlined the mechanisms related to increase of neurotrophic factors, Schwann cells activation, and cellular signaling activation for cell activation and mitosis induced by low-intensity extracorporeal shockwave therapy. We searched PubMed for articles related to research on these topics in both in vitro and in vivo animal models and found numerous studies suggesting that the application low-intensity extracorporeal shockwave therapy could be a novel treatment for erectile dysfunction induced by nerve injury and other disease related to nerve injury.

Deciphering the myth of icariin and synthetic derivatives in improving erectile function from a molecular biology perspective: a narrative review.

Background and Objective: Although epimedium herb (EH) has been widely used in ancient Chinese medicine to enhance sexual activity, its pharmacological mechanism is not clear. Modern studies have shown that epimedium herb is rich in icariin (ICA, a flavonoid compound), and 91.2% of icariin is converted to icariside II (ICA II) by hydrolytic enzymes in intestinal bacteria after oral administration. YS-10 is a synthetic derivative of icariside II. The aim of this review was to summarize the contemporary evidence regarding the pharmacokinetics, therapeutic properties, and molecular biological mechanisms of ICA and some ICA derivatives for erectile dysfunction therapy. Methods: A detailed search was conducted in the PubMed database using keywords and phrases, such as "icariin" AND "erectile dysfunction", "icariside II" AND "erectile dysfunction". The publication time is limited to last 20 years. Articles had to be published in peer reviewed journals. Key Content and Findings: ICA and its some derivatives showed the specific inhibition on phosphodiesterase type 5 (PDE5) and the promotion of testosterone synthesis. In addition, by regulating various reliable evidence of signaling pathways such as PI3K/AKT, TGFß1/Smad2, p38/MAPK, Wnt and secretion of various cytokines, ICA and ICA derivatives can activate endogenous stem cells (ESCs) leading to endothelial cell and smooth muscle cell proliferation, nerve regeneration and fibrosis inhibition, repair pathological changes in penile tissue and improve erectile function. Conclusions: ICA and some of its derivatives could be a potential treatment for restoring spontaneous erections. In addition ICA and his derivatives may also be valuable as a regenerative medicine approach for other diseases, but more clinical and basic researches with high quality and large samples are recommended.

The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial.

BACKGROUND: A recent sham-controlled clinical study has shown that low-intensity pulsed ultrasound twice per week can safely and effectively treat patients with mild-to-moderate erectile dysfunction (ED). However, large-scale clinical trials are needed to verify its efficacy and safety and determine a reasonable treatment interval. AIM: To study whether low-intensity pulsed ultrasound therapy thrice per week is non-inferior to twice per week in patients with mild-to-moderate ED. METHODS: A randomized, open-label, parallel-group, non-inferiority clinical trial was conducted in 7 hospitals in China. A total of 323 patients with mild-to-moderate ED were randomized (1:1) into thrice per week (3/W) and twice per week (2/W) groups. Low-intensity pulsed ultrasound was applied on each side of the penis for 16 sessions. OUTCOMES: The primary outcome was response rate using the minimal clinically important difference in the International Index of Erectile Function (IIEF-EF) score at week 12. Secondary outcomes included Erection Hardness Score (EHS), Sexual Encounter Profile, Global Assessment Question, and Self Esteem and Relationship Questionnaire. RESULTS: Response rates in 3/W and 2/W groups were 62.0% and 62.5%, respectively. Treatment effect in the 3/W group was noninferior to that of the 2/W group, with rate difference lower bound of -0.01% [95% confidence interval -0.11 to 0.10%] within the acceptable margin (-14.0%). No significant difference was found among secondary outcomes. IIEF-EF score showed a significant increase from baseline in the 3/W group (16.8 to 20.7) and 2/W group (17.8 to 21.7), and the percentage of patients with EHS ≥3 increased in the 3/W (54.9% to 84.0%) and 2/W (59.5% to 83.5%) groups. There was no significant difference in response rate between the 2 groups after controlling for strata factors and homogeneous tests. No treatment-related adverse events were reported. CLINICAL IMPLICATIONS: Low-intensity pulsed ultrasound therapy displays similar efficacy and safety for mild-to-moderate ED when administered thrice or twice per week for 16 sessions. This study provides two options to suit patients' needs. STRENGTHS & LIMITATIONS: This is a large-sample, randomized, controlled, noninferiority trial study. Short-term follow-up and mostly younger patients are the main limitations. CONCLUSION: Low-intensity pulsed ultrasound therapy thrice and twice per week showed equivalent therapeutic effects and safety for mild-to-moderate ED in a young and generally healthy population. This therapy warrants further investigation of its potential value in rehabilitation of ED. Chen, H., Li Z., Li X., et al. The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial. J Sex Med 2022;19:1536-1545.

Single-cell transcriptome atlas of the human corpus cavernosum.

The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.

Microenergy acoustic pulse therapy restores function and structure of pelvic floor muscles after simulated birth injury.

Background: The mechanisms of the microenergy acoustic pulse (MAP) therapy on restoring structure and function of pelvic floor muscles (PFM) after simulated birth injury are not well understood. Methods: A total 24 female Sprague-Dawley rats were randomly grouped into sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + ß-aminopropionitrile (BAPN, an irreversible LOX inhibitor), and VBDO + BAPN and treated with MAP (n=6 in each group). The MAP therapy was administered 2 times per week for 4 weeks with 1-week washout, the functional and histological studies were conducted in all 24 rats. The viscoelastic behavior of the PFM, including iliococcygeus (IC) and pubococcygeus (PC), was examined with a biomechanical assay. The structure of the PFM was assessed by immunofluorescence and Masson's trichrome staining. Results: The leak point pressure (LPP) assay demonstrated that the MAP therapy group had higher LPPs compared to that of VBDO and BAPN groups. In the sham group, the muscular stiffness (K) of IC muscle was significantly higher than that of PC muscle while the pelvic floor muscle rebound activity (MRA) of PC muscle was stronger than that of IC muscle (291.26±45.33 and 241.18±14.23 N/cm2, respectively). Both VBDO and BAPN decreased the MRA and increased the K in both IC and PC. Histologic examination revealed increased fibrous tissue (collagen) and degeneration of muscle fibers in both VBDO and BAPN groups. MAP therapy significantly reduced the collagen content and improved the architecture of muscle fibers. Conclusions: MAP appears to restore the structure and function of PFM by regenerating muscular fibers and improving biomechanical properties in an animal model of simulated birth injury.

Enhanced Myogenesis by Silencing Myostatin with Nonviral Delivery of a dCas9 Ribonucleoprotein Complex.

Stress urinary incontinence (SUI) and pelvic floor disorder (PFD) are common conditions with limited treatment options in women worldwide. Regenerative therapy to restore urethral striated and pelvic floor muscles represents a valuable therapeutic approach. We aim to determine the CRISPR interference-mediated gene silencing effect of the nonviral delivery of nuclease-deactivated dCas9 ribonucleoprotein (RNP) complex on muscle regeneration at the cellular and molecular level. We designed four myostatin (MSTN)-targeting sgRNAs and transfected them into rat myoblast L6 cells together with the dCas9 protein. Myogenesis assay and immunofluorescence staining were performed to evaluate muscle differentiation, while CCK8 assay, cell cycle assay, and 5-ethynyl-2'-deoxyuridine staining were used to measure muscle proliferation. Reverse transcription-polymerase chain reaction and Western blotting were also performed to examine cellular signaling. Myogenic factors (including myosin heavy chain, MSTN, myocardin, and serum response factor) increased significantly after day 5 during myogenesis. MSTN was efficiently silenced after transfecting the dCas9 RNP complex, which significantly promoted more myotube formation and a higher fusion index for L6 cells. In cellular signaling, MSTN repression enhanced the expression of MyoG and MyoD, phosphorylation of Smad2, and the activity of Wnt1/GSK-3ß/ß-catenin pathway. Moreover, MSTN repression accelerated L6 cell growth with a higher cell proliferation index as well as a higher expression of cyclin D1 and cyclin E. Nonviral delivery of the dCas9 RNP complex significantly promoted myoblast differentiation and proliferation, providing a promising approach to improve muscle regeneration for SUI and PFD. Further characterization and validation of this approach in vivo are needed.

Microenergy acoustic pulse therapy restores urethral wall integrity and continence in a rat model of female stress incontinence.

OBJECTIVE: To determine the outcomes and mechanisms of microenergy acoustic pulse (MAP) therapy in an irreversible rat model of female stress urinary incontinence. MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats were randomly assigned into four groups: sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + ß-aminopropionitrile (BAPN), and VBDO + ß-aminopropionitrile treated with MAP (MAP). MAP therapy was administered twice per week for 4 weeks. After a 1-week washout period, all 24 rats were evaluated with functional and histological studies. The urethral vascular plexus was examined by immunofluorescence staining with antibodies against collagen IV and von Willebrand factor (vWF). The urethral smooth muscle stem/progenitor cells (uSMPCs) were isolated and functionally studied in vivo and in vitro. RESULTS: Functional study with leak point pressure (LPP) measurement showed that the MAP group had significantly higher LPPs compared to VBDO and BAPN groups. MAP ameliorated the decline in urethral wall thickness and increased the amount of extracellular matrix within the urethral wall, especially in the urethral and vaginal elastic fibers. MAP also improved the disruption of the urethral vascular plexus in the treated animals. In addition, MAP enhanced the regeneration of urethral and vaginal smooth muscle, and uSMPCs could be induced by MAP to differentiate into smooth muscle and neuron-like cells in vitro. CONCLUSION: MAP appears to restore urethral wall integrity by increasing muscle content in the urethra and the vagina and by improving the urethral vascular plexus and the extracellular matrix.

Microenergy acoustic pulses promotes muscle regeneration through in situ activation of muscle stem cells.

Microenergy acoustic pulses (MAP) is a modified low-intensity extracorporeal shock wave therapy that currently used for treating musculoskeletal disorders. However, its function on muscle regeneration after ischemia-reperfusion injury (IRI) remains unknown. This study aimed to explore the effect of MAP on muscle injury after IRI and its underlying mechanisms. Ten-week-old C57BL/6J mice underwent unilateral hindlimb IRI followed with or without MAP treatment. Wet weight of tibialis anterior muscles at both injury and contralateral sides were measured followed with histology analysis at 3 weeks after IRI. In in vitro study, the myoblasts, endothelial cells and fibro-adipogenic progenitors (FAP) were treated with MAP. Cell proliferation and differentiation were assessed, and related gene expressions were measured by real-time PCR. Our results showed that MAP significantly increased the muscle weight and centrally nucleated regenerating muscle fiber size along with a trend in activating satellite cells. In vitro data indicated that MAP promoted myoblast proliferation and differentiation and endothelial cells migration. MAP also induced FAP brown/beige adipogenesis, a promyogenic phenotype of FAPs. Our findings demonstrate the beneficial function of MAP in promoting muscle regeneration after IR injury by inducing muscle stem cells proliferation and differentiation.

Mineralized Peyronie's plaque has a phenotypic resemblance to bone.

Mineralized Peyronie's plaque (MPP) impairs penile function. The association, colocalization, and dynamic interplay between organic and inorganic constituents can provide insights into biomineralization of Peyronie's plaque. Human MPPs (n = 11) were surgically excised, and the organic and inorganic constituents were spatially mapped using multiple high-resolution imaging techniques. Multiscale image analyses resulted in spatial colocalization of elements within a highly porous material with heterogenous composition, lamellae, and osteocytic lacuna-like features with a morphological resemblance to bone. The lower (520 ±â€¯179 mg/cc) and higher (1024 ±â€¯155 mg/cc) mineral density regions were associated with higher (11%) and lower (7%) porosities in MPP. Energy dispersive X-ray and micro-X-ray fluorescent spectroscopic maps in the higher mineral density regions of MPP revealed higher counts of calcium (Ca) and phosphorus (P), and a Ca/P ratio of 1.48 ±â€¯0.06 similar to bone. More importantly, higher counts of zinc (Zn) were localized at the interface between softer (more organic to inorganic ratio) and harder (less organic to inorganic ratio) tissue regions of MPP and adjacent softer matrix, indicating the involvement of Zn-related proteins and/or pathways in the formation of MPP. In particular, dentin matrix protein-1 (DMP-1) was colocalized in a matrix rich in proteoglycans and collagen that contained osteocytic lacuna-like features. This combined materials science and biochemical with correlative microspectroscopic approach provided insights into the plausible cellular and biochemical pathways that incite mineralization of an existing fibrous Peyronie's plaque. STATEMENT OF SIGNIFICANCE: Aberrant human penile mineralization is known as mineralized Peyronie's plaque (MPP) and often results in a loss of form and function. This study focuses on investigating the spatial association of matrix proteins and elemental composition of MPP by colocalizing calcium, phosphorus, and trace metal zinc with dentin matrix protein 1 (DMP-1), acidic proteoglycans, and fibrillar collagen along with the cellular components using high resolution correlative microspectroscopy techniques. Spatial maps provided insights into cellular and biochemical pathways that incite mineralization of fibrous Peyronie's plaque in humans.