<b>Context and Aim:</b> Mesenchymal stem cells (MSCs) and platelet-rich fibrin (PRF) have emerged as ideal candidates for advanced therapies of various therapeutically-challenging diseases;however, their r...<b>Context and Aim:</b> Mesenchymal stem cells (MSCs) and platelet-rich fibrin (PRF) have emerged as ideal candidates for advanced therapies of various therapeutically-challenging diseases;however, their regenerative potential in diabetic foot ulcers (DFU) has not been well determined. In this study, we reviewed our clinical experience in mitigating chronic ulcer complications of diabetic foot through a conventional treatment of autologous adipose-derived MSCs embedded in PRF with pure PRF injections. <b>Materials and Methods:</b> The present study was carried out in 10 patients with an open DFU wound selected over a period of 1 year starting from April 2019. Patients were either injected with PRF alone (Group A) or injected with MSCs derived from adipose tissue (ADMSC) embedded in (PRF (Group B). <b>Results:</b> Patients in Group B had a better healing index when compared to Group A. <b>Conclusion:</b> Use of ADMSC embedded in PRF showed promising results to treat DFU.展开更多
This work focuses to improve the mechanical properties and investigates the growth of osteoblasts on a degradable chitosan/poly(L-lactide)/carbon nanotubes composite for tissue engineering. The morphological and mecha...This work focuses to improve the mechanical properties and investigates the growth of osteoblasts on a degradable chitosan/poly(L-lactide)/carbon nanotubes composite for tissue engineering. The morphological and mechanical properties characterizations were performed using scanning electronic microscopy (SEM) and rheometrics analysis system (RSA). Osteoblasts differentiation was determined by alkaline phosphatase activity, total number cells by an Alamar Blue assay, cell attachment and proliferation were visualized qualitatively using SEM, mineralization was characterized by transformed infrared spectroscopy, energy dispersive spectroscopy, and X-ray diffraction. The results suggest that the chitosan/poly(L-lactide)/multiwalled carbon nanotubes composites exhibit the ability to promote cell adhesion, proliferation, and differentiation on their surface.展开更多
Tetraethyl orthosilicate (TEOS) and trimethyl orthosilicate (TMOS) alkoxysilanes are expensive common precursors for silicate based solgel derived bioactive glasses. Facile approa- ches involving low cost substitutes ...Tetraethyl orthosilicate (TEOS) and trimethyl orthosilicate (TMOS) alkoxysilanes are expensive common precursors for silicate based solgel derived bioactive glasses. Facile approa- ches involving low cost substitutes are a necessity for bioactive glass implants in bone regeneration therapy. Quaternary SiO2–Na2O–CaO– P2O5 bioactive glass was prepared by the solgel method from locally sourced sand as precursor. The monolith glass material obtained was subjected to immersion studies in simulated body fluid (SBF) for 21 days. The surface morphology and composition of the glass before and after immersion in SBF was studied using SEM-EDX, while pH analysis was used to monitor changes on the glass surface in SBF solution. FTIR was used to confirm apatite formation on the material. Results showed that the concentration of Ca, P and C increased on the surface of the glass sample as immersion time increased, which was attributed to the formation of carbonated hydroxyapatite (HCA). The material shows ability to bond to bone making it a promising scaffold material for bone repair.展开更多
Background: Chronic knee pain from advanced osteoarthritis is often associated with tears in the fibro-cartilaginous meniscus and cruciate ligaments. The result is substantial pain and impairments and loss of daily fu...Background: Chronic knee pain from advanced osteoarthritis is often associated with tears in the fibro-cartilaginous meniscus and cruciate ligaments. The result is substantial pain and impairments and loss of daily function, thus limiting activity and quality of life. These often include pain, loss of range of 116 motion, inability to elevate the leg, pain increased with activity and gradual worsening over time. This represents a challenging clinical picture for which few non-surgical options are available. Most patients failing to respond to current methods of care are offered arthroplasty. Current therapies are focused on the relief of the symptoms but cannot repair the damage nor stop the degenerative process. Objective: This is a case study of the first subject in a continuing IRB to reach a 2.5 year end-point. Our intention was to investigate the potential benefits of using autologous, minimally manipulated fat graft in subjects with advanced osteoarthritis and meniscus pathology who had failed to obtain benefit from previous, standards of care. Study description: 73 YO male, end stage bone-on-bone right knee pain. First subject to reach the 2 1/2 year follow up after Lipogems®?precision ultrasound guided injections. Material and Methods: Micro-fragmented fat was obtained using a minimal manipulation technology in a closed system, Lipogems®, without the addition of enzymes or other additives. Fat graft was injected under continuous ultrasound guidance. Results: VAS pain, KOOS function, range of motion and quadriceps strength improved after treatment. Conclusion: Autologous, micronized, and minimally manipulated adipose tissue resulted in significant improvement in pain, function and quality of life. No adverse events were reported.展开更多
Background and Aims: On November 24, 2009, Huu S. TIEU and Golden Sunrise Pharmaceutical, Inc. (Golden Sunrise) applied for the Technology and Innovation to be reviewed and evaluated by the U.S. Food and Drug Administ...Background and Aims: On November 24, 2009, Huu S. TIEU and Golden Sunrise Pharmaceutical, Inc. (Golden Sunrise) applied for the Technology and Innovation to be reviewed and evaluated by the U.S. Food and Drug Administration (FDA). In the review and evaluation, it was requested by Golden Sunrise designated the new indications for this application under Serious or Life-threatening conditions or diseases. Discussions followed with the FDA, Huu S. TIEU, and Golden Sunrise for FDA approval on new products and new indications on existing new Medical Technology and Innovation. It was agreed in Year-2015 that the FDA would take the request for new indications to the United States Congress to establish into FDA regulation and law. At that time the following was the FDA Guidance—“Emergency Use of a Test Article” is exempt from prior Institutional Review Board or Advisory Committee evaluation and approval, provided that such emergency use is reported to the Institutional Review Board within five working days after use. Expedited Institutional Review Board or Advisory Committee approval is not permitted in emergency use. There has been no funding to the authors for the writing or publication of this article. Methods: It was requested by Huu S. TIEU and Golden Sunrise in documents given to the FDA to have Serious or Life-threatening conditions or diseases indication be recognized by law. On August 08, 2015, the FDA responding to this request took the documentation produced by Golden Sunrise to the United States Congress on behalf of Golden Sunrise and Huu S. TIEU. This article encompasses the FDA regulatory method as well as the discussion and results of the establishment of the FDA and the 21<sup>st</sup> Century Cures Act. Results: On December 13, 2016, H.R.34—114<sup>th</sup> United States Congress (2015-2016) 21<sup>st</sup> Century CURES Act was signed into law by President Barack H. Obama which included the Serious or Life-threatening indication to be written into the CURES Act. In summary, the 21<sup>st</sup> Century Cures Act is a landmark piece of legislation that enjoyed broad bipartisan support in United States Congress. The main goals of the Act are impactful and should transform future cancer, neurologic, and precision medicine or drug research as well as aid individuals with mental health is intended to facilitate the prompt approval of new agents and devices, clinicians should be aware of the types of data behind an approval and take this into consideration when developing illnesses and opioid dependence. However, some of the wording within the CURES Act regarding the drug and device approval process may bring pause to health care providers including pharmacists. Although this wording and implementing care plans and counseling patients. The 21<sup>st</sup> Century Cures Act was incorporated into laws and regulations by the FDA under § 3072 of the Act grants the Commissioner of Food and Drugs the authority to appoint and set the annual rate of pay for outstanding and qualified candidates to scientific, technical, or professional positions that support the development, review, and regulation of medical products.展开更多
Macrophages have recently been characterized as having an M1 or M2 phenotype based on receptor expression, mechanism of activation and function. The effects of macrophage phenotype upon tissue remodeling following imp...Macrophages have recently been characterized as having an M1 or M2 phenotype based on receptor expression, mechanism of activation and function. The effects of macrophage phenotype upon tissue remodeling following implantation of an acellular dermal matrix (ADM) is largely unknown. The purpose of this study was to compare the macrophage phenotype and tissue remodeling elicited by four different ADMs (DermaMatrix, AlloDerm, Integra and Der mACELL). ADM samples were wrapped around the inferior epigastric vessels of a rat and were harvested on 7, 14, 21 and 42 days post implantation. Immunohistologic methods were used to identify macrophage surface markers CD68 (pan macrophage), CCR7 (M1 profile), and CD206 (M2 profile). All human derived ADMs showed a bell shaped curve for distribution of CD68+ macrophages with peaks for DermaMatrix occurring at day 14 and peak influx for AlloDerm occurring on day 21. In contrast, bovine derived Integra showed an increasing trend of macrophages with time. DermACELL had the highest influx of macro- phages while Integra had the lowest. A quantitative analysis of phenotype of macrophages in AlloDerm showed that the cells were predominantly M1 at 7, 14, 21 and 42 days post implantation. In contrast, Integra showed a mixed M1/M2 population of macrophages at all time points. The histopathologic evaluation showed that a predominantly M1 macrophage response was associated with a more inflamematory type tissue remodeling outcome in AlloDerm while a mixed M1/M2 macrophage response was associated with a more constructive tissue remodeling response seen in the other substrates.展开更多
The field of therapeutic angiogenesis has been predominantly concentrated in modalities that incorporate pro-angiogenic growth factors and/or cells within polymeric constructs that are implanted into the ischemic regi...The field of therapeutic angiogenesis has been predominantly concentrated in modalities that incorporate pro-angiogenic growth factors and/or cells within polymeric constructs that are implanted into the ischemic region. There is growing evidence that construct architecture can significantly affect growth factor activity, cellular viability and differentiation potential. Electrospinning is an attractive but simple scaffold fabrication technique that offers several advantages over traditional fabrication approaches to prepare highly organized structures for therapeutic angiogenesis applications. We recently described the fabrication of nanofibrous scaffolds with aligned fiber orientation that directed cell migration and orientation (i.e.human umbilical vein endothelial cells). Herein we demonstrate the ability of bFGF containing nanofibrous gelatin B scaffolds with controlled fiber orientation to promote capillary formation in vivo. Aligned scaffolds loaded with bFGF induced the highest levels of reperfusion (73% increased in LDPI ratios by day 21 post ischemia induction) in comparison to all other groups including scaffolds with random fiber orientation. Furthermore, the newly formed vasculature, assessed by confocal microscopy, had a parallel alignment along the axis of the scaffold’s fibers. In contrast, no vessel directionality was observed in the animals treated with scaffolds with random fiber orientation in the presence or absence of bFGF.展开更多
Purpose: Prolotherapy is a therapeutic method that involves injecting an irritant substance into injured areas of tendons, ligaments, and articular spaces. It has a wide application in orthopedic fields, including art...Purpose: Prolotherapy is a therapeutic method that involves injecting an irritant substance into injured areas of tendons, ligaments, and articular spaces. It has a wide application in orthopedic fields, including arthritis, tendinopathies, and back pain. Protocol of injection varies extensively based on the pathological condition. This review aims to discuss orthopedic applications of prolotherapy and its related outcomes, intending to introduce more specific injection protocols in each field. Methods: In a narrative review of literature, various musculoskeletal indications and contraindications of prolotherapy, as well as the method and location of injection, solution type, procedure intervals and frequencies, outcomes and side effects are investigated to reveal all aspects of the current knowledge about this new approach. Results: Chronic back pain, osteoarthritis, and tendinopathies are considered the most common indications for prolotherapy. Protocol of injection varies from one condition to another. The actual concentration of administered dextrose ranges from 12.5% to 25%. Results of the different studies indicate that prolotherapy could have a pleasing effect on improving patient’s pain and functional outcomes. No severe complication has been mentioned in previous investigations. Conclusion: Prolotherapy is a new therapeutic option that can be suggested as an effective method in recalcitrant musculoskeletal conditions.展开更多
Background: The number of people presenting with osteoarthritis is increasing due, largely, to an ageing population and advances in medical treatments. This is driving the demand for new clinical solutions and treatme...Background: The number of people presenting with osteoarthritis is increasing due, largely, to an ageing population and advances in medical treatments. This is driving the demand for new clinical solutions and treatments for the disease. Biologic therapies have been touted as an adjunct, or even alternative to established treatments for osteoarthritis. The term “biologics” refers to protein-based therapeutics that are derived from the proteins of living organisms. These treatments include, but are not limited to: autologous blood products such as platelet rich plasma (PRP), cell therapies such as autologous chondrocyte implantation (ACI) and mesenchymal stem cells, growth factors and cytokines, gene therapy. Aim: This study aims to provide a clear definition of these technologies and describe the evidence supporting their clinical efficacy to treat osteoarthritis. This is to provide clarity to both clinicians and patients on the range of technologies available. Method: Literature databases Embase and PubMed were searched for keywords such as “biologic”, “osteoarthritis”. Results: The literature identified 4 primary categories of biologic treatments for osteoarthritis: stem cell therapy, somatic cell therapy, protein therapy and gene therapy. The evidence level varied in its quality from treatment to treatment, as did the conclusions of published studies. Conclusion: Autologous chondrocyte therapy had the most convincing evidence to support its use as a treatment for osteoarthritis, however, current methods of use produced variable results. Other treatments such as platelet rich plasma and bone marrow derived stem cells show promise as potential future therapies, with more refinement, but evidence does not support their use currently. Other treatments including autologous stem cells should be avoided until there is a greater quantity and quality of evidence supporting their use.展开更多
The human dermis presents an ongoing problem for regenerative medicine. Current medical management uses various acellular dermal matrices on wound sites. The challenge for scientists is to examine, then to question ac...The human dermis presents an ongoing problem for regenerative medicine. Current medical management uses various acellular dermal matrices on wound sites. The challenge for scientists is to examine, then to question accepted conventional wisdom and to present new concepts. In this paper, Autologous Cell Therapy will be described by using cell culture of autologous dermal fibroblasts and their extracellular matrix as a foundation for rebuilding the dermis in conditioned wound beds. This proposal seems to create a conflict with the medical approach to keeping a wound bed “moist”.展开更多
Stem cell therapy is a relatively new treatment modality in the field of regenerative medicine. The therapy is gaining increased awareness and acceptance by the public. There are multiple factors that contribute to a ...Stem cell therapy is a relatively new treatment modality in the field of regenerative medicine. The therapy is gaining increased awareness and acceptance by the public. There are multiple factors that contribute to a stem cell procedure for regenerative medicine in order for it to be successful. One of these factors is a patient’s mental health and psychological state. The role and significance of a counsellor/psychologist will be examined as a crucial part of the regenerative medicine team. Pre-existing issues of depression, anxiety, post-traumatic stress disorder (PTSD), addiction, low self-esteem and high levels of stress could adversely affect outcomes. For example, fears and phobias are counter-productive for planned regenerative therapy. The counsellor must also assess and determine that the patient is mentally and psychologically healthy. In addition, advice is necessary for the patient to have realistic expectations in order for them to be eligible for treatment. Some patients are not suitable for stem cells and other regenerative procedures until psychological treatment is successful, particularly in body image dysmorphia. A comprehensive psychological assessment is needed and answers must be provided for patients by the counsellor during all phases of the treatment.展开更多
Titanium is widely used in biomedical applications from many years for its interesting properties, nevertheless there are a large number of researchers studying the way to improve the performances of biomedical device...Titanium is widely used in biomedical applications from many years for its interesting properties, nevertheless there are a large number of researchers studying the way to improve the performances of biomedical devices. A large number of papers concern the study of “commercially pure titanium” (Ti CP) but, very often, no details are indicated regarding: 1) the type of Ti CP used;2) the sandblasting process;and 3) the analytic evaluation of surface topography. In this paper, the effect of sandblasting duration (1, 2, 4, 8 min) and hydrofluoric acid (HF) etching, as well as their combined or synergic effect, on the surface topography of CP grade 2 and grade 4, have been investigated. Results obtained show that sandblasting treatment duration should be different for Ti CP grade 2 and Ti CP grade 4 to achieve similar topography. The shape of the surface is highly modified after acid etching. The latter produces “peaks” when applied to not sand- blasted coupons, whilst cuts the “top of the peaks” in the sandblasted samples. Further we confirm that, the roughness parameter Ra (or Sa), is not sufficient to describe “the surface status” and we propose to use additional para- meters like: Sq, Sku and Ssk, to unequivocally describe surface topography of implants as well as well defined test procedures.展开更多
This paper provides an overview of the conventional therapeutic stimulation methodologies and proposes a more effective stimulation approach based on a consideration of the inherently fractal nature of normal biologic...This paper provides an overview of the conventional therapeutic stimulation methodologies and proposes a more effective stimulation approach based on a consideration of the inherently fractal nature of normal biological dynamics. There are varying forms of physiological stimulations including the use of electrical currents, electromagnetic fields, temperature change, ultrasound, light and so forth. These stimulation therapies can be categorized into three main modalities: electrical stimulation modalities, thermal modalities, and non-thermal modalities. Electrical stimulation modalities include therapeutic techniques where electrical current is directly applied to the body of treated subject. Direct application of electrical current to the brain also falls under this category. Thermal modalities consist of stimulations that induce temperature change on the body for therapeutic effects without the direct transfer of electrical current. Non-thermal modalities functions through energy transfer without directly applying electrical current and without the effects of temperature change. A fourth miscellaneous category for stimulation techniques consists of the stimulation effects of music along with physical stimulation as in massage therapy. Common to most of these therapeutic strategies is that the stimulation is delivered at certain fixed periods or frequencies. We introduce some rudiments of fractal dynamics, and the notions of self-similarity, scale-invariance, and long-range correlation or memory in the dynamics of a system. We present evidence that fractal dynamics is commonly observed in healthy physiological systems while unhealthy systems are shown to veer away from fractal dynamics towards periodic or random motion. This difference in dynamics can be observed in many biological signals such as in neural activity, heart rate variations, and breathing patterns. We propose that an optimal stimulation technique should thus be one that encourages an unhealthy, non-fractal pathological system towards a healthy, fractal dynamic. Given the ubiquity of fractality in healthy biological dynamics, we argue that a fractal pattern of stimulation is a more optimal approach to functional restoration than the widely used conventional periodic stimulation, which may further consolidate the existing pathological dynamics.展开更多
Objective: To evaluate the efficacy based on clinical symptom and on magnetic resonance image of platelet-rich plasma therapy in combination with mesenchymal stem cells from autologous adipose tissue for knee osteoart...Objective: To evaluate the efficacy based on clinical symptom and on magnetic resonance image of platelet-rich plasma therapy in combination with mesenchymal stem cells from autologous adipose tissue for knee osteoarthritis treatment. Patients and Method: 30 patients including 26 females and 4 males;correspondingly, 60 knee joints were diagnosed with osteoarthritis with stages II - III of Kellgren and Lawrence, their mean age was 58.63 ± 11.11. All were injected with autologous platelet-rich plasma that was extracted by PRP set, APC 30 PRP PRCEDURE PRAK and autologously extracted mesenchymal stem cells from abdominal adipose tissue using the ADI-25-01 ADIPOSEPRCEDURE PRAK of USA. Results: After 12 months: the pain level according to VAS score at the right knee joint was decreased from 6.0 ± 1.28 before treatment to 1.9 ± 0.3;VAS score at the left knee joint was decreased from 6.43 ± 1.19 to 2.25 ± 0.43. Total Lequene score at right knee joint was decreased from 16.04 ± 1.57 before treatment to 4.31 ± 1.04, at left knee joint was decreased from 17.52 ± 1.74 before treatment to 5.15 ± 1.48. Total WOMAC score at right knee joint was decreased from 55.93 ± 5.56 to 10.37 ± 1.56;at left knee joint was decreased from 53.97 ± 5.57 to 10.07 ± 1.59. There were 86.77% joints with cartilage thickness change and the patellar cartilage thickness was increased from 1.56 ± 0.09 mm before treatment to 1.65 ± 0.09 mm. Conclusion: The treatment of knee osteoarthritis by platelet-rich plasma therapyin combination with mesenchymal stem cells from autologous adipose tissue is effective in reducing pain, improving patient's mobility and walking function, reforming articular cartilage thickness on magnetic resonance image.展开更多
Aim & Background: It was proposed that the differences in erythrocyte membrane protein contents—especially band 4—take a role in the serious anemia related to interferon plus ribavirin (I/R). The aim of this stu...Aim & Background: It was proposed that the differences in erythrocyte membrane protein contents—especially band 4—take a role in the serious anemia related to interferon plus ribavirin (I/R). The aim of this study is to evaluate whether the erythrocyte membrane protein contents predict anemia related to I/R or not. Methods: 180 mcg interferon α 2a once a week and weight adjusted ribavirin daily were given for 48 weeks to fifty patients with chronic hepatitis C. It was diagnosed as anemia when haemoglobin concentration was Results: Anemia developed in 17 patients (34%). The levels of erythrocyte membrane proteins were as;spectrin: 20.468 ± 2.5902, ankyrin: 4.576 ± 1.2706, B3: 19.240 ± 2.8358, B4.1: 5.628 ± 1.8832, and B4.2: 5.848 ± 1.8030. When the relation between the development of anemia and erythrocyte membrane proteins was investigated, a relation was only found at B3 which was not statistically significant (p = 0.058). When ROC analysis was performed, 95% CI p = 0.035 for B3 (0.517 - 0.792) was found. In patients whose B3 level was below 17.7%, the sensitivity of anemia development risk was calculated as 64.7% and the specificity thereof was calculated as 66.7%. Erythrocyte membrane protein contents by gender were only different at B3 (p = 0.042). Anemia developed in 17 patients (34%). 14 of these patients were of female and 3 were of male gender;the gender played a significant role in terms of anemia (p = 0.003). Conclusions: Erythrocyte membrane protein B3 is not only useful in predicting the patient under the risk of developing anemia, but also it may be useful in preventing it and it may explain why women inclined to anemia.展开更多
Skin grafts have remained relatively unchanged since their introduction as a medical treatment for burns/wounds. This paper seeks to open an academic discussion as to whether their use-by date has now been passed. A s...Skin grafts have remained relatively unchanged since their introduction as a medical treatment for burns/wounds. This paper seeks to open an academic discussion as to whether their use-by date has now been passed. A skin graft substitute is described in a paradigm using fine leaf gelatine sheets which inherently possess several distinct advantages including, discarding the harvest of autologous tissue from patient donor sites. A clinical study will be needed to determine its suitability taken together with the understanding that experimental animal studies may not provide unequivocal answers to its in situ modus operandi.展开更多
Platelet rich plasma (PRP) contains a high concentration of thrombocytes and the a granules of platelets contain platelet released growth factors. The usefulness of PRP for regeneration of bone and soft tissues has be...Platelet rich plasma (PRP) contains a high concentration of thrombocytes and the a granules of platelets contain platelet released growth factors. The usefulness of PRP for regeneration of bone and soft tissues has been reported previously. We firstly reported the efficacy of PRP prepared using the Magellan Autologous Platelet Separator System for intractable skin ulcers such as diabetic and venous ulcers. The system consists of a microprocessor controlled centrifuge, syringe pumps, and necessary single use processing components. No complications occurred in any patients and the wounds achieved complete epithelialization. Our results have shown the efficiency of platelet rich plasma for the treatment of intractable skin ulcers.展开更多
It is well known that small biomaterial particles can lead to superior properties demanded by advanced applications in tissue engineering. Electrospraying has been considered as a promising approach to prepare fine pa...It is well known that small biomaterial particles can lead to superior properties demanded by advanced applications in tissue engineering. Electrospraying has been considered as a promising approach to prepare fine particles, but reducing the particle size during such jetting process is always challenging. This is because the size of the as-sprayed particles is always limited by the device outlet diameter used. In the study we show that hydroxyapatite (HA) relics of 2 - 3 μm with low standard deviation can be deposited using a large nozzle (diameter of 1100 μm) only by reducing the nozzle tip angle from 90° to 15°. The mechanism of such phenomenon was extensively discussed, and a range of refined HA patterns were successfully prepared using the updated electrspraying configuration. We anticipate our findings to have a significant impact on the research of nanostructured biomaterials with superior properties which are realized by reducing the particle size using a greener electrically-driven processing technique.展开更多
Combining different areas of regenerative medicine is considered the new standard for comprehensive tissue and organ regeneration. This approach can be further applied to cosmetic issues such as deep neck lines. This ...Combining different areas of regenerative medicine is considered the new standard for comprehensive tissue and organ regeneration. This approach can be further applied to cosmetic issues such as deep neck lines. This case report utilized techniques of autologous stem cell therapy and epigenetic tissue environment modulation with externally applied polyphenols and tissue penetration agents. The results showed a remarkable cosmetic improvement with a significant reduction of neck lines in a patient where employment and psychological issues were developing from the original problem. The regenerative medicine protocol was safe, efficient in disposable materials, portable benchtop equipment and surgical operating time. The patient had an excellent outcome for this difficult to treat cosmetic problem.展开更多
This study evaluated the capability of hydroxyapatite fiber (HAF) as a carrier and the bone formation by blending simvastatin. The mixture of HAF and simvastatin (0.15, 0.45, 0.75 mg) was placed in 1 ml of tris-buffer...This study evaluated the capability of hydroxyapatite fiber (HAF) as a carrier and the bone formation by blending simvastatin. The mixture of HAF and simvastatin (0.15, 0.45, 0.75 mg) was placed in 1 ml of tris-buffer and the release of simvastatin from HAF was calculated per 24 hours for 10 days. Bilateral 5 mm-diameter and 3 mm-hight Teflon chambers were fixed on calvaria of adult Japanese white rabbits and filled with 40 mg HAF which containing simvastatin (0, 0.15, 0.45, 0.75 mg). The animals were sacrificed at 4 and 8 weeks and calculated radiologically by Micro-CT. After dyeing by toluidine blue the samples were analyzed histologically. In all of the study groups approximately 25% of simvastatin was released until 10 days. The new bone volume ratio measured by Micro-CT of 4 and 8 weeks group was (22.4%, 21.3%, 41.6%, 26.3%) and (20.2%, 11.7%, 42.1%, 31.2%) in different doses respectively. The 0.45 mg group showed significantly higher new bone volume ratio than 0 mg group and 0.15 mg group. The histological measurement and observations also supported these results. In conclusion, the HAF could be used as a carrier for simvastatin. Combinations of HAF and simvastatin have the potentiality to stimulate new bone formation and approximately 0.45 mg simvastatin in 40 mg HAF is the optimal dose in rabbit chamber model.展开更多
文摘<b>Context and Aim:</b> Mesenchymal stem cells (MSCs) and platelet-rich fibrin (PRF) have emerged as ideal candidates for advanced therapies of various therapeutically-challenging diseases;however, their regenerative potential in diabetic foot ulcers (DFU) has not been well determined. In this study, we reviewed our clinical experience in mitigating chronic ulcer complications of diabetic foot through a conventional treatment of autologous adipose-derived MSCs embedded in PRF with pure PRF injections. <b>Materials and Methods:</b> The present study was carried out in 10 patients with an open DFU wound selected over a period of 1 year starting from April 2019. Patients were either injected with PRF alone (Group A) or injected with MSCs derived from adipose tissue (ADMSC) embedded in (PRF (Group B). <b>Results:</b> Patients in Group B had a better healing index when compared to Group A. <b>Conclusion:</b> Use of ADMSC embedded in PRF showed promising results to treat DFU.
文摘This work focuses to improve the mechanical properties and investigates the growth of osteoblasts on a degradable chitosan/poly(L-lactide)/carbon nanotubes composite for tissue engineering. The morphological and mechanical properties characterizations were performed using scanning electronic microscopy (SEM) and rheometrics analysis system (RSA). Osteoblasts differentiation was determined by alkaline phosphatase activity, total number cells by an Alamar Blue assay, cell attachment and proliferation were visualized qualitatively using SEM, mineralization was characterized by transformed infrared spectroscopy, energy dispersive spectroscopy, and X-ray diffraction. The results suggest that the chitosan/poly(L-lactide)/multiwalled carbon nanotubes composites exhibit the ability to promote cell adhesion, proliferation, and differentiation on their surface.
文摘Tetraethyl orthosilicate (TEOS) and trimethyl orthosilicate (TMOS) alkoxysilanes are expensive common precursors for silicate based solgel derived bioactive glasses. Facile approa- ches involving low cost substitutes are a necessity for bioactive glass implants in bone regeneration therapy. Quaternary SiO2–Na2O–CaO– P2O5 bioactive glass was prepared by the solgel method from locally sourced sand as precursor. The monolith glass material obtained was subjected to immersion studies in simulated body fluid (SBF) for 21 days. The surface morphology and composition of the glass before and after immersion in SBF was studied using SEM-EDX, while pH analysis was used to monitor changes on the glass surface in SBF solution. FTIR was used to confirm apatite formation on the material. Results showed that the concentration of Ca, P and C increased on the surface of the glass sample as immersion time increased, which was attributed to the formation of carbonated hydroxyapatite (HCA). The material shows ability to bond to bone making it a promising scaffold material for bone repair.
文摘Background: Chronic knee pain from advanced osteoarthritis is often associated with tears in the fibro-cartilaginous meniscus and cruciate ligaments. The result is substantial pain and impairments and loss of daily function, thus limiting activity and quality of life. These often include pain, loss of range of 116 motion, inability to elevate the leg, pain increased with activity and gradual worsening over time. This represents a challenging clinical picture for which few non-surgical options are available. Most patients failing to respond to current methods of care are offered arthroplasty. Current therapies are focused on the relief of the symptoms but cannot repair the damage nor stop the degenerative process. Objective: This is a case study of the first subject in a continuing IRB to reach a 2.5 year end-point. Our intention was to investigate the potential benefits of using autologous, minimally manipulated fat graft in subjects with advanced osteoarthritis and meniscus pathology who had failed to obtain benefit from previous, standards of care. Study description: 73 YO male, end stage bone-on-bone right knee pain. First subject to reach the 2 1/2 year follow up after Lipogems®?precision ultrasound guided injections. Material and Methods: Micro-fragmented fat was obtained using a minimal manipulation technology in a closed system, Lipogems®, without the addition of enzymes or other additives. Fat graft was injected under continuous ultrasound guidance. Results: VAS pain, KOOS function, range of motion and quadriceps strength improved after treatment. Conclusion: Autologous, micronized, and minimally manipulated adipose tissue resulted in significant improvement in pain, function and quality of life. No adverse events were reported.
文摘Background and Aims: On November 24, 2009, Huu S. TIEU and Golden Sunrise Pharmaceutical, Inc. (Golden Sunrise) applied for the Technology and Innovation to be reviewed and evaluated by the U.S. Food and Drug Administration (FDA). In the review and evaluation, it was requested by Golden Sunrise designated the new indications for this application under Serious or Life-threatening conditions or diseases. Discussions followed with the FDA, Huu S. TIEU, and Golden Sunrise for FDA approval on new products and new indications on existing new Medical Technology and Innovation. It was agreed in Year-2015 that the FDA would take the request for new indications to the United States Congress to establish into FDA regulation and law. At that time the following was the FDA Guidance—“Emergency Use of a Test Article” is exempt from prior Institutional Review Board or Advisory Committee evaluation and approval, provided that such emergency use is reported to the Institutional Review Board within five working days after use. Expedited Institutional Review Board or Advisory Committee approval is not permitted in emergency use. There has been no funding to the authors for the writing or publication of this article. Methods: It was requested by Huu S. TIEU and Golden Sunrise in documents given to the FDA to have Serious or Life-threatening conditions or diseases indication be recognized by law. On August 08, 2015, the FDA responding to this request took the documentation produced by Golden Sunrise to the United States Congress on behalf of Golden Sunrise and Huu S. TIEU. This article encompasses the FDA regulatory method as well as the discussion and results of the establishment of the FDA and the 21<sup>st</sup> Century Cures Act. Results: On December 13, 2016, H.R.34—114<sup>th</sup> United States Congress (2015-2016) 21<sup>st</sup> Century CURES Act was signed into law by President Barack H. Obama which included the Serious or Life-threatening indication to be written into the CURES Act. In summary, the 21<sup>st</sup> Century Cures Act is a landmark piece of legislation that enjoyed broad bipartisan support in United States Congress. The main goals of the Act are impactful and should transform future cancer, neurologic, and precision medicine or drug research as well as aid individuals with mental health is intended to facilitate the prompt approval of new agents and devices, clinicians should be aware of the types of data behind an approval and take this into consideration when developing illnesses and opioid dependence. However, some of the wording within the CURES Act regarding the drug and device approval process may bring pause to health care providers including pharmacists. Although this wording and implementing care plans and counseling patients. The 21<sup>st</sup> Century Cures Act was incorporated into laws and regulations by the FDA under § 3072 of the Act grants the Commissioner of Food and Drugs the authority to appoint and set the annual rate of pay for outstanding and qualified candidates to scientific, technical, or professional positions that support the development, review, and regulation of medical products.
文摘Macrophages have recently been characterized as having an M1 or M2 phenotype based on receptor expression, mechanism of activation and function. The effects of macrophage phenotype upon tissue remodeling following implantation of an acellular dermal matrix (ADM) is largely unknown. The purpose of this study was to compare the macrophage phenotype and tissue remodeling elicited by four different ADMs (DermaMatrix, AlloDerm, Integra and Der mACELL). ADM samples were wrapped around the inferior epigastric vessels of a rat and were harvested on 7, 14, 21 and 42 days post implantation. Immunohistologic methods were used to identify macrophage surface markers CD68 (pan macrophage), CCR7 (M1 profile), and CD206 (M2 profile). All human derived ADMs showed a bell shaped curve for distribution of CD68+ macrophages with peaks for DermaMatrix occurring at day 14 and peak influx for AlloDerm occurring on day 21. In contrast, bovine derived Integra showed an increasing trend of macrophages with time. DermACELL had the highest influx of macro- phages while Integra had the lowest. A quantitative analysis of phenotype of macrophages in AlloDerm showed that the cells were predominantly M1 at 7, 14, 21 and 42 days post implantation. In contrast, Integra showed a mixed M1/M2 population of macrophages at all time points. The histopathologic evaluation showed that a predominantly M1 macrophage response was associated with a more inflamematory type tissue remodeling outcome in AlloDerm while a mixed M1/M2 macrophage response was associated with a more constructive tissue remodeling response seen in the other substrates.
文摘The field of therapeutic angiogenesis has been predominantly concentrated in modalities that incorporate pro-angiogenic growth factors and/or cells within polymeric constructs that are implanted into the ischemic region. There is growing evidence that construct architecture can significantly affect growth factor activity, cellular viability and differentiation potential. Electrospinning is an attractive but simple scaffold fabrication technique that offers several advantages over traditional fabrication approaches to prepare highly organized structures for therapeutic angiogenesis applications. We recently described the fabrication of nanofibrous scaffolds with aligned fiber orientation that directed cell migration and orientation (i.e.human umbilical vein endothelial cells). Herein we demonstrate the ability of bFGF containing nanofibrous gelatin B scaffolds with controlled fiber orientation to promote capillary formation in vivo. Aligned scaffolds loaded with bFGF induced the highest levels of reperfusion (73% increased in LDPI ratios by day 21 post ischemia induction) in comparison to all other groups including scaffolds with random fiber orientation. Furthermore, the newly formed vasculature, assessed by confocal microscopy, had a parallel alignment along the axis of the scaffold’s fibers. In contrast, no vessel directionality was observed in the animals treated with scaffolds with random fiber orientation in the presence or absence of bFGF.
文摘Purpose: Prolotherapy is a therapeutic method that involves injecting an irritant substance into injured areas of tendons, ligaments, and articular spaces. It has a wide application in orthopedic fields, including arthritis, tendinopathies, and back pain. Protocol of injection varies extensively based on the pathological condition. This review aims to discuss orthopedic applications of prolotherapy and its related outcomes, intending to introduce more specific injection protocols in each field. Methods: In a narrative review of literature, various musculoskeletal indications and contraindications of prolotherapy, as well as the method and location of injection, solution type, procedure intervals and frequencies, outcomes and side effects are investigated to reveal all aspects of the current knowledge about this new approach. Results: Chronic back pain, osteoarthritis, and tendinopathies are considered the most common indications for prolotherapy. Protocol of injection varies from one condition to another. The actual concentration of administered dextrose ranges from 12.5% to 25%. Results of the different studies indicate that prolotherapy could have a pleasing effect on improving patient’s pain and functional outcomes. No severe complication has been mentioned in previous investigations. Conclusion: Prolotherapy is a new therapeutic option that can be suggested as an effective method in recalcitrant musculoskeletal conditions.
文摘Background: The number of people presenting with osteoarthritis is increasing due, largely, to an ageing population and advances in medical treatments. This is driving the demand for new clinical solutions and treatments for the disease. Biologic therapies have been touted as an adjunct, or even alternative to established treatments for osteoarthritis. The term “biologics” refers to protein-based therapeutics that are derived from the proteins of living organisms. These treatments include, but are not limited to: autologous blood products such as platelet rich plasma (PRP), cell therapies such as autologous chondrocyte implantation (ACI) and mesenchymal stem cells, growth factors and cytokines, gene therapy. Aim: This study aims to provide a clear definition of these technologies and describe the evidence supporting their clinical efficacy to treat osteoarthritis. This is to provide clarity to both clinicians and patients on the range of technologies available. Method: Literature databases Embase and PubMed were searched for keywords such as “biologic”, “osteoarthritis”. Results: The literature identified 4 primary categories of biologic treatments for osteoarthritis: stem cell therapy, somatic cell therapy, protein therapy and gene therapy. The evidence level varied in its quality from treatment to treatment, as did the conclusions of published studies. Conclusion: Autologous chondrocyte therapy had the most convincing evidence to support its use as a treatment for osteoarthritis, however, current methods of use produced variable results. Other treatments such as platelet rich plasma and bone marrow derived stem cells show promise as potential future therapies, with more refinement, but evidence does not support their use currently. Other treatments including autologous stem cells should be avoided until there is a greater quantity and quality of evidence supporting their use.
文摘The human dermis presents an ongoing problem for regenerative medicine. Current medical management uses various acellular dermal matrices on wound sites. The challenge for scientists is to examine, then to question accepted conventional wisdom and to present new concepts. In this paper, Autologous Cell Therapy will be described by using cell culture of autologous dermal fibroblasts and their extracellular matrix as a foundation for rebuilding the dermis in conditioned wound beds. This proposal seems to create a conflict with the medical approach to keeping a wound bed “moist”.
文摘Stem cell therapy is a relatively new treatment modality in the field of regenerative medicine. The therapy is gaining increased awareness and acceptance by the public. There are multiple factors that contribute to a stem cell procedure for regenerative medicine in order for it to be successful. One of these factors is a patient’s mental health and psychological state. The role and significance of a counsellor/psychologist will be examined as a crucial part of the regenerative medicine team. Pre-existing issues of depression, anxiety, post-traumatic stress disorder (PTSD), addiction, low self-esteem and high levels of stress could adversely affect outcomes. For example, fears and phobias are counter-productive for planned regenerative therapy. The counsellor must also assess and determine that the patient is mentally and psychologically healthy. In addition, advice is necessary for the patient to have realistic expectations in order for them to be eligible for treatment. Some patients are not suitable for stem cells and other regenerative procedures until psychological treatment is successful, particularly in body image dysmorphia. A comprehensive psychological assessment is needed and answers must be provided for patients by the counsellor during all phases of the treatment.
文摘Titanium is widely used in biomedical applications from many years for its interesting properties, nevertheless there are a large number of researchers studying the way to improve the performances of biomedical devices. A large number of papers concern the study of “commercially pure titanium” (Ti CP) but, very often, no details are indicated regarding: 1) the type of Ti CP used;2) the sandblasting process;and 3) the analytic evaluation of surface topography. In this paper, the effect of sandblasting duration (1, 2, 4, 8 min) and hydrofluoric acid (HF) etching, as well as their combined or synergic effect, on the surface topography of CP grade 2 and grade 4, have been investigated. Results obtained show that sandblasting treatment duration should be different for Ti CP grade 2 and Ti CP grade 4 to achieve similar topography. The shape of the surface is highly modified after acid etching. The latter produces “peaks” when applied to not sand- blasted coupons, whilst cuts the “top of the peaks” in the sandblasted samples. Further we confirm that, the roughness parameter Ra (or Sa), is not sufficient to describe “the surface status” and we propose to use additional para- meters like: Sq, Sku and Ssk, to unequivocally describe surface topography of implants as well as well defined test procedures.
文摘This paper provides an overview of the conventional therapeutic stimulation methodologies and proposes a more effective stimulation approach based on a consideration of the inherently fractal nature of normal biological dynamics. There are varying forms of physiological stimulations including the use of electrical currents, electromagnetic fields, temperature change, ultrasound, light and so forth. These stimulation therapies can be categorized into three main modalities: electrical stimulation modalities, thermal modalities, and non-thermal modalities. Electrical stimulation modalities include therapeutic techniques where electrical current is directly applied to the body of treated subject. Direct application of electrical current to the brain also falls under this category. Thermal modalities consist of stimulations that induce temperature change on the body for therapeutic effects without the direct transfer of electrical current. Non-thermal modalities functions through energy transfer without directly applying electrical current and without the effects of temperature change. A fourth miscellaneous category for stimulation techniques consists of the stimulation effects of music along with physical stimulation as in massage therapy. Common to most of these therapeutic strategies is that the stimulation is delivered at certain fixed periods or frequencies. We introduce some rudiments of fractal dynamics, and the notions of self-similarity, scale-invariance, and long-range correlation or memory in the dynamics of a system. We present evidence that fractal dynamics is commonly observed in healthy physiological systems while unhealthy systems are shown to veer away from fractal dynamics towards periodic or random motion. This difference in dynamics can be observed in many biological signals such as in neural activity, heart rate variations, and breathing patterns. We propose that an optimal stimulation technique should thus be one that encourages an unhealthy, non-fractal pathological system towards a healthy, fractal dynamic. Given the ubiquity of fractality in healthy biological dynamics, we argue that a fractal pattern of stimulation is a more optimal approach to functional restoration than the widely used conventional periodic stimulation, which may further consolidate the existing pathological dynamics.
文摘Objective: To evaluate the efficacy based on clinical symptom and on magnetic resonance image of platelet-rich plasma therapy in combination with mesenchymal stem cells from autologous adipose tissue for knee osteoarthritis treatment. Patients and Method: 30 patients including 26 females and 4 males;correspondingly, 60 knee joints were diagnosed with osteoarthritis with stages II - III of Kellgren and Lawrence, their mean age was 58.63 ± 11.11. All were injected with autologous platelet-rich plasma that was extracted by PRP set, APC 30 PRP PRCEDURE PRAK and autologously extracted mesenchymal stem cells from abdominal adipose tissue using the ADI-25-01 ADIPOSEPRCEDURE PRAK of USA. Results: After 12 months: the pain level according to VAS score at the right knee joint was decreased from 6.0 ± 1.28 before treatment to 1.9 ± 0.3;VAS score at the left knee joint was decreased from 6.43 ± 1.19 to 2.25 ± 0.43. Total Lequene score at right knee joint was decreased from 16.04 ± 1.57 before treatment to 4.31 ± 1.04, at left knee joint was decreased from 17.52 ± 1.74 before treatment to 5.15 ± 1.48. Total WOMAC score at right knee joint was decreased from 55.93 ± 5.56 to 10.37 ± 1.56;at left knee joint was decreased from 53.97 ± 5.57 to 10.07 ± 1.59. There were 86.77% joints with cartilage thickness change and the patellar cartilage thickness was increased from 1.56 ± 0.09 mm before treatment to 1.65 ± 0.09 mm. Conclusion: The treatment of knee osteoarthritis by platelet-rich plasma therapyin combination with mesenchymal stem cells from autologous adipose tissue is effective in reducing pain, improving patient's mobility and walking function, reforming articular cartilage thickness on magnetic resonance image.
文摘Aim & Background: It was proposed that the differences in erythrocyte membrane protein contents—especially band 4—take a role in the serious anemia related to interferon plus ribavirin (I/R). The aim of this study is to evaluate whether the erythrocyte membrane protein contents predict anemia related to I/R or not. Methods: 180 mcg interferon α 2a once a week and weight adjusted ribavirin daily were given for 48 weeks to fifty patients with chronic hepatitis C. It was diagnosed as anemia when haemoglobin concentration was Results: Anemia developed in 17 patients (34%). The levels of erythrocyte membrane proteins were as;spectrin: 20.468 ± 2.5902, ankyrin: 4.576 ± 1.2706, B3: 19.240 ± 2.8358, B4.1: 5.628 ± 1.8832, and B4.2: 5.848 ± 1.8030. When the relation between the development of anemia and erythrocyte membrane proteins was investigated, a relation was only found at B3 which was not statistically significant (p = 0.058). When ROC analysis was performed, 95% CI p = 0.035 for B3 (0.517 - 0.792) was found. In patients whose B3 level was below 17.7%, the sensitivity of anemia development risk was calculated as 64.7% and the specificity thereof was calculated as 66.7%. Erythrocyte membrane protein contents by gender were only different at B3 (p = 0.042). Anemia developed in 17 patients (34%). 14 of these patients were of female and 3 were of male gender;the gender played a significant role in terms of anemia (p = 0.003). Conclusions: Erythrocyte membrane protein B3 is not only useful in predicting the patient under the risk of developing anemia, but also it may be useful in preventing it and it may explain why women inclined to anemia.
文摘Skin grafts have remained relatively unchanged since their introduction as a medical treatment for burns/wounds. This paper seeks to open an academic discussion as to whether their use-by date has now been passed. A skin graft substitute is described in a paradigm using fine leaf gelatine sheets which inherently possess several distinct advantages including, discarding the harvest of autologous tissue from patient donor sites. A clinical study will be needed to determine its suitability taken together with the understanding that experimental animal studies may not provide unequivocal answers to its in situ modus operandi.
文摘Platelet rich plasma (PRP) contains a high concentration of thrombocytes and the a granules of platelets contain platelet released growth factors. The usefulness of PRP for regeneration of bone and soft tissues has been reported previously. We firstly reported the efficacy of PRP prepared using the Magellan Autologous Platelet Separator System for intractable skin ulcers such as diabetic and venous ulcers. The system consists of a microprocessor controlled centrifuge, syringe pumps, and necessary single use processing components. No complications occurred in any patients and the wounds achieved complete epithelialization. Our results have shown the efficiency of platelet rich plasma for the treatment of intractable skin ulcers.
文摘It is well known that small biomaterial particles can lead to superior properties demanded by advanced applications in tissue engineering. Electrospraying has been considered as a promising approach to prepare fine particles, but reducing the particle size during such jetting process is always challenging. This is because the size of the as-sprayed particles is always limited by the device outlet diameter used. In the study we show that hydroxyapatite (HA) relics of 2 - 3 μm with low standard deviation can be deposited using a large nozzle (diameter of 1100 μm) only by reducing the nozzle tip angle from 90° to 15°. The mechanism of such phenomenon was extensively discussed, and a range of refined HA patterns were successfully prepared using the updated electrspraying configuration. We anticipate our findings to have a significant impact on the research of nanostructured biomaterials with superior properties which are realized by reducing the particle size using a greener electrically-driven processing technique.
文摘Combining different areas of regenerative medicine is considered the new standard for comprehensive tissue and organ regeneration. This approach can be further applied to cosmetic issues such as deep neck lines. This case report utilized techniques of autologous stem cell therapy and epigenetic tissue environment modulation with externally applied polyphenols and tissue penetration agents. The results showed a remarkable cosmetic improvement with a significant reduction of neck lines in a patient where employment and psychological issues were developing from the original problem. The regenerative medicine protocol was safe, efficient in disposable materials, portable benchtop equipment and surgical operating time. The patient had an excellent outcome for this difficult to treat cosmetic problem.
文摘This study evaluated the capability of hydroxyapatite fiber (HAF) as a carrier and the bone formation by blending simvastatin. The mixture of HAF and simvastatin (0.15, 0.45, 0.75 mg) was placed in 1 ml of tris-buffer and the release of simvastatin from HAF was calculated per 24 hours for 10 days. Bilateral 5 mm-diameter and 3 mm-hight Teflon chambers were fixed on calvaria of adult Japanese white rabbits and filled with 40 mg HAF which containing simvastatin (0, 0.15, 0.45, 0.75 mg). The animals were sacrificed at 4 and 8 weeks and calculated radiologically by Micro-CT. After dyeing by toluidine blue the samples were analyzed histologically. In all of the study groups approximately 25% of simvastatin was released until 10 days. The new bone volume ratio measured by Micro-CT of 4 and 8 weeks group was (22.4%, 21.3%, 41.6%, 26.3%) and (20.2%, 11.7%, 42.1%, 31.2%) in different doses respectively. The 0.45 mg group showed significantly higher new bone volume ratio than 0 mg group and 0.15 mg group. The histological measurement and observations also supported these results. In conclusion, the HAF could be used as a carrier for simvastatin. Combinations of HAF and simvastatin have the potentiality to stimulate new bone formation and approximately 0.45 mg simvastatin in 40 mg HAF is the optimal dose in rabbit chamber model.
