Hydrogels for tissue engineering.

Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.

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Hydrogels in regenerative medicine

Designing of biologically active scaffolds with optimal characteristics is one of the key factors for successful tissue engineering. Recently, hydrogels have received a considerable interest as leading candidates for engineered tissue scaffolds due to their unique compositional and structural similarities to the natural extracellular matrix, in addition to their desirable framework for cellular proliferation and survival. More recently, the ability to control the shape, porosity, surface morphology, and size of hydrogel scaffolds has created new opportunities to overcome various challenges in tissue engineering such as vascularization, tissue architecture and simultaneous seeding of multiple cells. This review provides an overview of the different types of hydrogels, the approaches that can be used to fabricate hydrogel matrices with specific features and the recent applications of hydrogels in tissue engineering. Special attention was given to the various design considerations for an efficient hydrogel scaffold in tissue engineering. Also, the challenges associated with the use of hydrogel scaffolds were described.

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Hydrogel scaffolds for tissue engineering: Progress and challenges

Background Bovine collagen is extensively used for facial soft tissue augmentation but provides only temporary correction and can cause hypersensitivity reactions. Hyaluronic acid derivatives potentially offer improved longevity of correction and a reduced risk of immunogenicity and hypersensitivity. Objective To compare the efficacy and safety of nonanimal stabilized hyaluronic acid gel (Restylane; Q-Med, Uppsala, Sweden) with that of bovine collagen (Zyplast) for treatment of nasolabial folds. Methods One hundred thirty-eight patients with prominent nasolabial folds were randomized to treatment with hyaluronic acid gel and bovine collagen on contralateral sides of the face. Treatments were repeated at 2-week intervals, as required, to achieve "optimal cosmetic result" (baseline). Outcomes were evaluated by a blinded investigator at 2, 4, and 6 months after baseline. Results Less injection volume was required for "optimal cosmetic result" with hyaluronic acid gel than with bovine collagen, and patients and investigators judged hyaluronic acid gel to be more effective in maintaining cosmetic correction. The investigator-based Wrinkle Severity Rating Scale and Global Aesthetic Improvement Scale assessments at 6 months after baseline indicated that hyaluronic acid gel was superior in 56.9% and 62.0% of patients, respectively, whereas bovine collagen was superior in 9.5% and 8.0% of patients, respectively. The frequency, intensity, and duration of local injection-site reactions were similar for the two products. Conclusion Nonanimal stabilized hyaluronic acid provides a more durable aesthetic improvement than bovine collagen and is well tolerated.

A Randomized, Double-Blind, Multicenter Comparison of the Efficacy and Tolerability of Restylane Versus Zyplast for the Correction of Nasolabial Folds

background. Nonanimal hyaluronic acid gel was recently developed for soft tissue augmentation and volume expansion and has been shown to offer several advantages in comparison to other augmentation materials. There are rare reports of adverse events believed to be secondary to trace amounts of proteins in the hyaluronic acid raw material. objective. To determine the safety profile of nonanimal stabilized hyaluronic acid gel (Restylane, Perlane, Restylane Fine Lines, Q-Med AB, Uppsala, Sweden) for soft tissue augmentation using a retrospective review of all adverse events data from Europe, Canada, Australia, South American, and Asia from 1999 and 2000. results. Data from an estimated 144,000 patients treated in 1999 indicated the major reaction to injectable hyaluronic acid was localized hypersensitivity reactions, occurring in approximately 1 of every 1400 patients treated. In 1999 there was an adverse event reported for 1 of every 650 patients (0.15%) treated. These were temporary events that included redness, swelling, localized granulomatous reactions, bacterial infection, as well as acneiform and cystic lesions. For 2000 there was an estimated 262,000 patients treated with hyaluronic acid gel. The total number of adverse events was 144, corresponding to one adverse event for every 1800 patients (0.06%) treated. The major adverse event was again hypersensitivity, occurring in 1 of every 5000 patients treated. conclusion. According to the reported worldwide adverse events data, hypersensitivity to nonanimal hyaluronic acid gel is the major adverse event and is most likely secondary to impurities of bacterial fermentation. According to data from 2000, the incidence of hypersensitivity appears to be declining after the

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Safety data of injectable nonanimal stabilized hyaluronic acid gel for soft tissue augmentation.

background.Several biomaterials are available for the purpose of soft tissue augmentation, but none of them has all the properties of the ideal filler material. The recent development of hyaluronic acid gels for dermal implantation give the physician new possibilities of effective treatment in this

Injectable Hyaluronic Acid Gel for Soft Tissue Augmentation: A Clinical and Histological Study

BACKGROUND Recent articles have introduced the novel concept of chemical lipolysis through local injections. Phosphatidylcholine is the active drug in the commercial preparation used for this purpose, but some studies have suggested that sodium deoxycholate, an excipient of the preparation, could be the real active substance.

AIM We decided to investigate whether phosphatidylcholine and sodium deoxycholate have any clinical efficacy in chemical lipolysis and their respective roles. We also studied the safety and side effects of the treatments.

MATERIALS AND METHODS Thirty-seven consecutive female patients were studied for the treatment of localized fat in gynoid lipodystrophy. Each patient received injections of a phosphatidylcholine/sodium deoxycholate preparation on one side and sodium deoxycholate on the contralateral side, each single patient being herself the control. Four treatments were carried out every 8 weeks in a double-blind, randomized fashion. Metric circumferential evaluations and photographic and ultrasonographic measurements throughout the study allowed for final judgment. A statistical evaluation concluded our study.

RESULTS An overall reduction of local fat was obtained in 91.9% of the patients without statistically significant differences between the treated sides. Reduction values on the phosphatidylcholine/sodium deoxycholate–treated sides are in the order of 6.46% metrically and 36.87% ultrasonographically, whereas on the deoxycholate-treated sides they are in the order of 6.77% metrically and 36.06% ultrasonographically. Both treatments, at the dose used in the study, proved safe in the short term. The most common side effects were local and few, but were more pronounced on the deoxycholate-treated sides. No laboratory test was carried out.

CONCLUSION Both treatments have shown moderate and equivalent efficacy in treating localized fat, with sodium deoxycholate having a slower postoperative resolution, suggesting that sodium deoxycholate could be sufficient by itself to determine fat cell destruction and that phosphatidylcholine could be useful for obtaining a later emulsification of the fat.

Phosphatidylcholine and sodium deoxycholate in the treatment of localized fat: a double-blind, randomized study.

Increased interest in regenerative medicine in the last few years was registered. In parallel, a progressive increase in injectable calcium hydroxylapatite (CaHA) applications has been observed due to its applications in skin rejuvenation. This study combined micro fragmented fatty tissue (FAT) grafting with the CAHA filler procedure to observe the biological effect on FAT. Each sample of micro fragmented adipose tissue harvested using the guided  Superficial Enhanced Fluid Fat Injection (guided SEFFI) technique were collected from 5 patients. The 5 samples were divided into aliquots to create two different experimental conditions: FAT and FAT combined with CaHA (FAT + R). Afterwards, the cellularity of mesenchymal phenotype and the in vitro differentiation capacity in mesenchymal lineages were assessed in both experimental conditions, FAT and FAT+R. Despite low cellularity observed for FAT+R compared to FAT, isolated cells could grow and expand in culture in both experimental conditions, thus proving their proliferative ability. Cells were proved to differentiate towards mesenchymal lineages, expressing mesenchymal markers by flow cytometry analysis. Combining emulsified harvested tissue prepared with guided SEFFI technique with CaHA products can be exploited to counteract the loss of volume and skin ageing of the human face and body. This approach to regenerative aesthetic treatment is a promising treatment for facial antiaging therapy.

Characterization of Adipose-Derived Mesenchymal Stem Cells from tissue harvested with the guided SEFFI technique and co-cultured with calcium hydroxyapatite

Bruno Bovani

Papers

Injectable Hyaluronic Acid Gel for Soft Tissue Augmentation: A Clinical and Histological Study

Phosphatidylcholine and sodium deoxycholate in the treatment of localized fat: a double-blind, randomized study.

Characterization of Adipose-Derived Mesenchymal Stem Cells from tissue harvested with the guided SEFFI technique and co-cultured with calcium hydroxyapatite