Release Of PDGF Research Articles

Duo-role Platelet-rich Plasma: temperature-induced fibrin gel and growth factors’ reservoir for microneedles to promote hair regrowth

IntroductionAlopecia concerns more than half our adult population. Platelet-rich plasma (PRP) has been applied in skin rejuvenation and hair loss treatment. However, the pain and bleeding during injection and the troublesome for fresh preparation of each action limit PRP’s in-depth applying dedication to clinics. ObjectivesWe report a temperature-sensitive PRP induced fibrin gel included in a detachable transdermal microneedle (MN) for hair growth. ResultsPRP gel interpenetrated with the photocrosslinkable gelatin methacryloyl (GelMA) to realize sustained release of growth factors (GFs) and led to 14% growth in mechanical strength of a single microneedle whose strength reached 1.21 N which is sufficient to penetrate the stratum corneum. PRP-MNs’ release of VEGF, PDGF, and TGF-β were characterized and quantitatively around the hair follicles (HFs) for 4–6 days consecutively. PRP-MNs promoted hair regrowth in mice models. From transcriptome sequencing, PRP-MNs induced hair regrowth through angiogenesis and proliferation. The mechanical and TGF-β sensitive gene Ankrd1 was significantly upregulated by PRP-MNs treatment. ConclusionPRP-MNs show convenient, minimally invasive, painless, inexpensive manufacture, storable and sustained effects in boosting hair regeneration.

Platelet rich fibrin containing nanofibrous dressing for wound healing application: Fabrication, characterization and biological evaluations

Recently, nanofibrous structures have shown great potential for a wide range of medical applications. The aim of the current study was to evaluate the wound healing process using Polycaprolactone/Keratin/Platelet-rich fibrin (PCL/Kr/PRF) fibrous scaffold fabricated through electrospinning process. A range of techniques were utilized to fully characterize the chemical, physical and biological properties of the resultant structure. Results revealed that by the addition of only 0.5%w/v PRF to PCL/Kr (PCL/Kr/0.5PRF) sample, the fibers diameter decreased from 193.93 ± 64.80 nm to 65.98 ± 14.03 nm, and the stress at break demonstrated a 18.27% increase in comparison to the PCL sample (from 2.90 ± 0.80 MPa to 3.43 ± 0.90 MPa). The PCL/Kr/0.5PRF scaffold showed more antibacterial activity against gram-positive and gram-negative bacteria than PCL/Kr sample. Based on enzyme-linked immunosorbent assays, the PCL/Kr/0.5PRF sample revealed an independent release of VEGF and PDGF for 7 days. Cell viability studies demonstrated non-cytotoxic nature of PRF-containing dressings. Also, chorioallantoic membrane (CAM) assay was performed to evaluate the angiogenic potential of the wound dressings. The in vivo assessments also showed that PCL/Kr/0.5PRF accelerated the wound healing process in terms of collagen deposition and the formation of skin appendages which was comparable to the normal skin. Overall, the data presented in this study greatly suggest that the PCL/Kr/0.5PRF wound dressing could be a suitable candidate for wound healing and skin regeneration.

Dual delivery of platelet-derived growth factor and bone morphogenetic factor-6 on titanium surface to enhance the early period of implant osseointegration.

To test the surface properties and in vitro effects of a new sequential release system on MC3T3-E1 cells for improved osseointegration. BMP6-loaded anodized titanium coated with PDGF containing silk fibroin (SF) may improve osseointegration. Titanium surfaces were electrochemically anodized, and SF layer was covered via electrospinning. Five experimental groups (unanodized Ti (Ti), anodized Ti (AnTi), anodized+BMP6-loaded Ti (AnTi-BMP6), anodized+BMP6 loaded+silk fibroin-coated Ti (AnTi-BMP6-SF), and anodized+BMP6-loaded+silk fibroin with PDGF-coated Ti (AnTi-BMP6-PDGF-SF)) were tested. After SEM characterization, contact angle analysis, and FTIR analysis, the amount of released PDGF and BMP6 was detected using ELISA. Cell proliferation (XTT), mineralization, and gene expression (RUNX2 and ALPL) were also evaluated. After successful anodization and loading of PDGF and BMP6, contact angle measurements showed hydrophobicity for TiO2 and hydrophilicity for protein-adsorbed surfaces. In FTIR, protein-containing surfaces exhibited amide-I, amide-II, and amide-III bands at 1600cm-1 -1700cm-1 , 1520cm-1 -1540cm-1 , and 1220cm-1 -1300cm-1 spectrum levels with a significant peak in BMP6- and/or SF-loaded groups at 1100cm-1 . PDGF release and BMP6 release were delayed, and relatively slower release was detected in SF-coated surfaces. Higher MC3T3-E1 proliferation and mineralization and lower gene expression of RUNX2 and ALPL were detected in AnTi-BMP6-PDGF-SF toward day 28. The new system revealed a high potential for an improved early osseointegration period by means of a better factor release curve and contribution to the osteoblastic cell proliferation, mineralization, and associated gene expression.

Dual release of VEGF and PDGF from emulsion electrospun bilayer scaffolds consisting of orthogonally aligned nanofibers for gastrointestinal tract regeneration

Abstract

The Role of Human Platelet Preparation for Toll-Like Receptors 2 and 4 Related Platelet Responsiveness.

Background Like immune cells, platelets express the repertoire of toll-like receptors (TLR), among them TLR2 and TLR4, which are important for the recognition of bacterial patterns. Receptor-mediated functional effects in platelets have been investigated, but reliable conclusions are tampered due to heterogeneous study designs with variable platelet preparation methods. This study compares TLR2- and TLR4-dependent platelet responsiveness in platelet-rich plasma (PRP) and in washed platelets (WPs). Material and Methods Fresh peripheral blood samples from healthy donors served for the preparation of PRP and WP. Basal and agonist-stimulated TLR2 and TLR4 expression levels were evaluated by flow cytometry. Light transmission aggregometry was used to investigate functional effects of TLR2 and TLR4 stimulation with Pam3CSK4 or LPS (lipopolysaccharides from Escherichia coli ) as ligands. The capacity of chemokine release was determined by immunoassays. Results Pam3CSK4 and LPS (in combination with thrombin) were able to induce aggregation in WP, but not in PRP, with threshold concentrations of 15 µg/mL. Basal expression levels of TLR2 and TLR4 were higher in WP than in PRP, increasing several-fold rapidly and persistently upon platelet activation with potent agonists. Pam3CSK4 (15 µg/mL) or LPS led to the submaximal release of RANTES, PF4, PDGF, NAP-2, and sCD40L from WP. In PRP, secretory effects are less pronounced for RANTES, PDGF, or PF4, and not detectable for NAP-2 or sCD40L. Conclusion The effects mediated by TLR2 and TLR4 stimulation are dependent on platelet preparation, an important issue for experimental designs and for manufacturing of platelet concentrates in transfusion medicine.

Lesion Dynamics Under Varying Paracrine PDGF Signaling in Brain Tissue.

Paracrine PDGF signaling is involved in many processes in the body, both normal and pathological, including embryonic development, angiogenesis, and wound healing as well as liver fibrosis, atherosclerosis, and cancers. We explored this seemingly dual (normal and pathological) role of PDGF mathematically by modeling the release of PDGF in brain tissue and then varying the dynamics of this release. Resulting simulations show that by varying the dynamics of a PDGF source, our model predicts three possible outcomes for PDGF-driven cellular recruitment and lesion growth: (1) localized, short duration of growth, (2) localized, chronic growth, and (3) widespread chronic growth. Further, our model predicts that the type of response is much more sensitive to the duration of PDGF exposure than the maximum level of that exposure. This suggests that extended duration of paracrine PDGF signal during otherwise normal processes could potentially lead to lesions having a phenotype consistent with pathologic conditions.

Inhibition of platelet-tumour cell interaction with ibrutinib reduces proliferation, migration and invasion of lung cancer cells

Purpose: To investigate the pharmacological role of the Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, in tumour cell-platelet crosstalk in lung cancer.Methods: Human lung cancer cells A549 were treated with ibrutinib or DMSO. mRNA expression was assessed using reverse transcription-quantitative polymerase chain reaction (RT-PCR), and while western blotting was used to determine protein expression levels. Small interfering RNA (siRNA) transfection was performed to suppress the expression of galectin-3. Colony formation and Transwell® assays were used to determine cell viability, cell invasiveness and migratory ability.Results: Co-culture of A549 cells and platelets induced activation of BTK/PLCγ2 signalling and subsequent release of PDGF, VEGF and TGFβ1 from de-granulated platelets. However, knocking down of galectin-3 inhibited A549-induced platelet activation. Conversely, platelet activation upregulated the expression of galectin-3 via the release of PDGF. Moreover, ibrutinib significantly (p < 0.05) inhibited cell viability, migration, and invasion.Conclusion: These results suggest that ibrutinib may be a novel therapeutic treatment for lung cancer.Keywords: Bruton tyrosine kinase, Ibrutinib, Lung cancer, Platelet

Local controlled release of simvastatin and PDGF from core/shell microspheres promotes bone regeneration in vivo

Simvastatin is demonstrated to be a potent stimulator for bone formation.

Regulation of sequential release of growth factors using bilayer polymeric nanoparticles for cardiac tissue engineering.

Cardiac tissue engineering aims to develop engineered constructs for myocardial infarction repair, where a challenge is the control of growth factor (GF) sequential release. Herein, bilayer polymeric nanoparticles composed of a GF-encapsulating core surrounded by rate-regulating shell were developed for sequential GF release. Single and bilayer polymeric nanoparticles were fabricated, characterized and biologically assessed. A novel 'Geno-Neural model' was developed and validated for rate-programming of the nanoparticles. The bilayer nanoparticles featured low burst effect and time-delayed release, and allowed for sequential release of PDGF following co-release of VEGFand bFGF, which promoted angiogenesis. The nanoparticulate delivery system, along with the Geno-Neural model, offers great potential for spatiotemporal control of GF release for cardiovascular regenerative medicine.

Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules.

Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl2, 10% of autologous thrombin, 10% of a mixture of CaCl2 + thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl2, thrombin, and CaCl2/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl2/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF-β 1 that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl2 induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic.

Sequential delivery of angiogenic growth factors improves revascularization and heart function after myocardial infarction

Treatment of ischemia through therapeutic angiogenesis faces significant challenges. Growth factor (GF)-based therapies can be more effective when concerns such as GF spatiotemporal presentation, bioactivity, bioavailability, and localization are addressed. During angiogenesis, vascular endothelial GF (VEGF) is required early to initiate neovessel formation while platelet-derived GF (PDGF-BB) is needed later to stabilize the neovessels. The spatiotemporal delivery of multiple bioactive GFs involved in angiogenesis, in a close mimic to physiological cues, holds great potential to treat ischemic diseases. To achieve sequential release of VEGF and PDGF, we embed VEGF in fibrin gel and PDGF in a heparin-based coacervate that is distributed in the same fibrin gel. In vitro, we show the benefits of this controlled delivery approach on cell proliferation, chemotaxis, and capillary formation. A rat myocardial infarction (MI) model demonstrated the effectiveness of this delivery system in improving cardiac function, ventricular wall thickness, angiogenesis, cardiac muscle survival, and reducing fibrosis and inflammation in the infarct zone compared to saline, empty vehicle, and free GFs. Collectively, our results show that this delivery approach mitigated the injury caused by MI and may serve as a new therapy to treat ischemic hearts pending further examination.

Modification of xenogenic bone substitute materials – effects on the early healing cascade in vitro

Initial platelet activation with subsequent cytokine release at the defect site plays a crucial role in tissue integration. The aim of this study was to evaluate the influence of topographic and biomimetic collagen modifications of a xenogenic bone substitute material (BSM) on in vitro platelet activation and cytokine release. Three types of xenogenic BSM were used. Two BSM with different levels of granularity (large granule BSM [XBSM/L], small granule BSM [XBSM/S]) and a BSM with collagen (XBSM/C). All three samples were incubated with platelet concentrate of four healthy volunteers at room temperature for 15min. For all groups, highly thrombogenic collagen type 1 served as a reference and an additional preparation with platelet concentrate only (without XBSM) served as control. Platelet count and cytokine release of VEGF, PDGF, TGF-β, and IGF into the supernatant were measured. Compared with the control group, XBSM/C showed an increase in platelets consumption (mean 41,000±26,000/ml vs. 471,000±38,000/ml), cytokine release of VEGF (mean 46.8±7.2pg/ml vs. 18.8±2.7pg/ml), and PDGF (mean 18,350±795pg/ml vs. 2726±410pg/ml) but not IGF (194,728±51,608pg/ml vs. 1,333,911±35,314pg/ml). There was also an increase in cytokine release of TGF-ß in XBSM/C compared with XBSM/S (77,188±27,413pg/ml vs. 38,648±13,191pg/ml), but no such difference when compared with XBSM/L (77,188±27,413pg/ml vs. 53,309±29,430pg/ml). XBSM/L showed higher platelets consumption (301,000±45,000 vs. 415,000±98,000) and a higher cytokine release of PDGF (3511±247pg/ml vs. 3165±78pg/ml) compared with XBSM/S. There was no distinct difference in the levels of VEGF, TGF-ß, and IGF between XBSM/L and XBSM/S. Topographic as well as biomimetic modifications of the xenogenic BSM showed an increased platelet activation and cytokine release in vitro. This effect on the intrinsic healing cascade could result in comparable enhanced soft- and hard-tissue regeneration in vivo.

Controlling the Proliferation and Differentiation Stages to Initiate Periodontal Regeneration

The success of periodontal regeneration depends on the coordination of early cell proliferation and late cell differentiation. The aim of this study was to investigate whether the proliferation or differentiation stage predominantly promotes the initiation of periodontal regeneration. Critical-sized periodontal defects were surgically created on rat maxillae and filled with poly-(d,l-lactide-co-glycolide)–poly-d,l-lactide hybrid microspheres encapsulating platelet-derived growth factor (PDGF, a promoter of mitogenesis), simvastatin (a promoter of osteogenic differentiation), or bovine serum albumin (a control). The encapsulation efficiency and in vitro release profiles of the microspheres were determined by high-performance liquid chromatography and enzyme-linked immunosorbent assay. The maxillae were harvested after 10 or 14 days and assessed by micro-computed tomography, histology, and immunohistochemistry for regeneration efficacy and cell viability. The rapid release of PDGF was observed within the first week, whereas a slow release profile was noted for simvastatin. The PDGF-treated specimens demonstrated a significantly higher bone volume fraction compared with bovine serum albumin– (p < 0.05) or simvastatin-treated (p < 0.05) specimens at day 14. Histologically, active bone formation originating from the defect borders was noted in both the PDGF- and the simvastatin-treated specimens, and functionally aligned periodontal ligament fiber insertion was only observed in the PDGF-treated specimens. The significant promotion of mitogenesis by PDGF treatment was also noted at day 14 (p < 0.05). In conclusion, increased mitogenesis or osteogenic differentiation may stimulate osteogenesis, and the upregulation of mitogenesis by PDGF appears to play a role in the initiation of periodontal regeneration.

Activation of Equine Platelet‐Rich Plasma: Comparison of Methods and Characterization of Equine Autologous Thrombin

To investigate and compare clinically relevant Platelet-rich plasma (PRP) activation methods. Experimental. PRP was prepared from 6 equine subjects. Activation of the PRP was performed by 4 methods (autologous thrombin, bovine thrombin, calcium chloride (CaCl(2) ), or freeze-thaw). The resultant PDGF-BB (where PDGF is platelet-derived growth factor) and TGFβ1 (where TGFβ is transforming growth factor beta) levels in PRP releasates were quantified by Enzyme-linked immunosorbent assay (ELISA) and compared. Growth factor contents were also compared between platelet-rich clots produced by thrombin or CaCl(2) . The composition and function of equine autologous thrombin were characterized by Western blot analysis and platelet aggregometry. CaCl(2) (23 mM) activation of PRP yielded significantly greater PDGF release than did any other method. TGFβ release was comparable after PRP activation by CaCl(2) , bovine thrombin, and freeze thaw. Autologous thrombin was significantly less effective than all other activation methods in eliciting platelet growth factor release and induced significantly less platelet aggregation than bovine thrombin at 5 U/mL. Clots retained substantial concentrations of growth factor, and the amount in the releasate versus the clot differed between activation methods. PRP activation methods differ in terms of growth factor output as well as logistical considerations. Autologous thrombin is not recommended for PRP activation. CaCl(2) (23 mM) is an effective and inexpensive method of PRP activation. The PRP releasate derived from CaCl(2) activation contains 80% of the total PDGF content and is easily produced, making it a convenient product for clinical use.

Blockade of PDGFR-β activation eliminates morphine analgesic tolerance

For centuries, opioid drugs have been the mainstay of chronic pain treatment. However, over time analgesic tolerance develops, leaving few treatment options. Here we show that platelet-derived growth factor receptor-β (PDGFR-β)-mediated signaling plays a key role in morphine tolerance. PDGFR-β inhibition selectively eliminates morphine tolerance in rats. PDGFR-β inhibitors are widely used and well tolerated, suggesting that clinical translation of our findings could reduce the suffering endured by individuals with intractable pain.

Effect of triple growth factor controlled delivery by a brushite–PLGA system on a bone defect

Bone regeneration is a complex process that involves multiple cell types, growth factors (GFs) and cytokines. A synergistic contribution of various GFs and a crosstalk between their signalling pathways was suggested as determinative for the overall osteogenic outcome.The purpose of this work was to develop a brushite–PLGA system, which controls the release rate of the integrated growth factors (GFs) to enhance bone formation.The brushite cement implants were prepared by mixing a phosphate solid phase with an acid liquid phase. PDGF (250ng) and TGF-β1 (100ng) were incorporated into the liquid phase. PLGA microsphere-encapsulated VEGF (350ng) was pre-blended with the solid phase. VEGF, PDGF and TGF-β1 release kinetics and tissue distributions were determined using iodinated (125I) GFs.In vivo results showed that PDGF and TGF-β1 were delivered more rapidly from these systems implanted in an intramedullary defect in rabbit femurs than VEGF. The three GFs released from the brushite–PLGA system remained located around the implantation site (5cm) with negligible systemic exposure. Bone peak concentrations of approximately 4ng/g and 1.5ng/g of PDGF and TGF-β1, respectively were achieved on day 3. Thereafter, PDGF and TGF-β1 concentrations stayed above 1ng/g during the first week. The scaffolds also provided a VEGF peak concentration of nearly 6ng/g on day 7 and a local concentration of approximately 1.5ng/g during at least 4 weeks. Four weeks post implantation bone formation was considerably enhanced with the brushite–PLGA system loaded with each of the three GFs separately as well as with the combination of PDGF and VEGF. The addition of TGF-β1 did not further improve the outcome.In conclusion, the herein presented brushite–PLGA system effectively controlled the release kinetics and localisation of the three GFs within the defect site resulting in markedly enhanced bone regeneration.

Platelet Activation by Collagen Provides Sustained Release of Anabolic Cytokines

Background: Platelet-rich plasma (PRP) has been increasingly used in sports medicine applications. Platelets are thought to release growth factors important in wound healing, including transforming growth factor (TGF-β1), platelet-derived growth factor (PDGF-AB), and vascular endothelial growth factor (VEGF). However, little is known about the effect of platelet activator choice on growth factor release kinetics. Hypothesis: The choice of platelet activator would affect the timing and level of growth factor release from PRP. Study Design: Controlled laboratory study. Methods: Platelet-rich plasma aliquots were activated with either thrombin or collagen. A control group of whole blood aliquots was clotted with thrombin. Supernatant containing the released growth factors was collected daily for 1 week. Levels of TGF-β1, PDGF-AB, and VEGF were measured using enzyme-linked immunosorbent assay (ELISA). Results: The use of thrombin as an activator resulted in immediate release of TGF-β1 and PDGF-AB, while the collagen-activated PRP clots released similar amounts each day for 5 days. The use of collagen as an activator resulted in an 80% greater cumulative release of TGF-β1 from the PRP aliquots over 7 days (P < .001). Concentrating platelets to 3 times the systemic blood level resulted in a 3-fold higher release of TGF-β1, 2.5-fold greater release of PDGF, and 5-fold greater release of VEGF (all P < .0001) when compared with whole blood control clots, but no significant differences in the timing of release were noted. Conclusion: These experiments demonstrated that the choice of platelet activator can significantly influence the release kinetics of cytokines from PRP, with thrombin resulting in an immediate release and collagen having a more sustained release pattern. Clinical Relevance: The level and rate of growth factor release depends on the selected platelet activator, a factor that should be considered when selecting a PRP system for a given application.

Evaluation of a filter-prepared platelet concentrate for the treatment of suspensory branch injuries in horses.

Platelet preparations have become a treatment for soft tissue injuries in horses. This study evaluated a novel filter-based system to concentrate platelets and assesses its value in the treatment of suspensory ligament branch desmitis. Filtered platelet concentrate was prepared from 55 ml of venous blood obtained from 21 normal horses. Platelets and white blood cells in whole blood and filtered platelet concentrate were measured, as was platelet activating factor (PAF)-induced platelet-derived growth factor-BB (PDGF-BB) release. Eleven horses with 18 focal acute suspensory ligament branch injuries were treated intra-lesionally with autologous filtered platelet concentrate and evaluated clinically and ultrasonographically for one to three years. The increase in concentration of platelets in the filtered concentrate in comparison with whole blood (6.9 ± 1.9-fold) was significantly greater than the increase in white blood cells (3.8 ± 0.8-fold) (p <0.0001). There was no effect of sex or breed on platelet concentration. Platelets were responsive to PAF with >100-fold higher levels of PDGF release over basal levels. All hypoechoic lesions re-evaluated within three months had resolved. Five of the 11 horses returned to their previous level of work, one was exercising at a lower level, three were retired, one died for unrelated reasons, and one was still convalescing. Filtered platelet concentrate was easily and reliably prepared and injected into suspensory ligament branch injuries without short-term complications. This treatment was associated with rapid resolution of ultrasonographic lesions and lameness. Filtered platelet concentrate represents a convenient alternative for the treatment of suspensory ligament branch injuries.

Local controlled release of VEGF and PDGF from a combined brushite–chitosan system enhances bone regeneration

The two growth factors VEGF and PDGF are involved in the process of bone regeneration. For this reason, we developed a brushite–chitosan system which controls the release kinetics of incorporated VEGF and PDGF to enhance bone healing. PDGF (250 ng) was incorporated in the liquid phase. Alginate microsphere-encapsulated VEGF (350 ng) was pre-included in small cylindrical chitosan sponges. VEGF and PDGF release kinetics and tissue distribution were determined using iodinated ( 125I) growth factor. In vivo, PDGF was more rapidly delivered from these systems implanted in rabbit femurs than VEGF. 80% of PDGF was released by the end of two weeks while only 70% of VEGF was delivered after a period of three weeks. Both GFs released from the brushite–chitosan constructs remained located around the implantation site (5 cm) with negligible systemic exposure. A PDGF bone peak concentration of approximately 5 ng/g was achieved on the 4th day. Thereafter, PDGF concentrations stayed higher than 2 ng/g during the first week. These scaffolds also provided a local VEGF bone concentration above 3 ng/g during a total of 4 weeks, with a peak concentration of 5.5 ng/g on the 7th day. The present work demonstrates that our brushite–chitosan system is capable of controlling the release rate and localization of both GFs within a bone defect. The effect on bone formation was considerably enhanced with PDGF loaded brushite–chitosan scaffolds as well as with the PDGF/VEGF combination.

Hyaluronan based porous nano-particles enriched with growth factors for the treatment of ulcers: a placebo-controlled study

The present study describes the production of hyaluronan based porous microparticles by a semi-continuous gas anti-solvent (GAS) precipitation process to be used as a growth factor delivery system for in vivo treatment of ulcers. Operative process conditions, such as pressure, nozzle diameter and HYAFF11 solution concentrations, were adjusted to optimize particle production in terms of morphology and size. Scanning electron microscopy (SEM) and light scattering demonstrated that porous nano-structured particles with a size of 300 and 900 nm had a high specific surface suitable for absorption of growth factors from the aqueous environment within the polymeric matrix. Water acted as a plasticizer, enhancing growth factor absorption. Water contents within the HYAFF11 matrix were analyzed by differential scanning calorimetry (DSC). The absorption process was developed using fluorescence dyes and growth factors. Immunohistochemical analysis confirmed the high efficiency of absorption of growth factor and a mathematical model was generated to quantify and qualify the in vitro kinetics of growth factor release within the polymeric matrix. In vivo experiments were performed with the aim to optimize timed and focal release of PDGF to promote optimal tissue repair and regeneration of full-thickness wounds.