Search

One of the promising approaches to facilitate healing and regenerative capacity includes the application of growth-factor-loaded biomaterials. Human platelet lysate (hPL) derived from platelet-rich plasma through a freeze-thaw process has been used as a growth factor rich therapeutic in many regenerative applications. To provide sustained local delivery of the hPL-derived growth factors such as epidermal growth factor (EGF), the hPL can be loaded into biomaterials that do not degrade rapidly in vivo. Keratin (KSO), a strong filamentous protein found in human hair, when formulated as a hydrogel, is shown to sustain the release of drugs and promote wound healing. In the current study, we created a KSO biomaterial that spontaneously forms a hydrogel when rehydrated with hPL that is capable of controlled and sustained release of pro-regenerative molecules. Our study demonstrates that the release of hPL is controlled by changing the KSO hydrogel and hPL-loading concentrations, with hPL loading concentrations having a greater effect in changing release profiles. In addition, the 15% KSO concentration proved to form a stable hydrogel, and supported cell proliferation over 3 days without cytotoxic effects in vitro. The hPL-loaded keratin hydrogels show promise in potential applications for wound healing with the sustained release of pro-regenerative growth factors with easy tailoring of hydrogel properties. more...

Ionizing radiation causes injury to the skin that produces a complex clinical presentation that is managed by various paradigms without clear standards. The situation is further complicated by the fact that clinicians and researchers often use different terms and billing codes to describe the spectrum of cutaneous injury. There is, however, general agreement between the two most commonly-used diagnostic scales, the Radiation Therapy Oncology Group and the Common Terminology Criteria for Adverse Events, and in their use to describe skin injury following radiation therapy. These scales are typically used by radiation oncologists to quantify radiation dermatitis, a component of the radiation-related disorders of the skin and subcutaneous tissue family of diagnoses. In rare cases, patients with severe injury may require treatment by wound care or burn specialists, in which case the disease is described as a “radiation burn” and coded as a burn or corrosion. Further compounding the issue, most US government agencies use the term Cutaneous Radiation Injury to indicate skin damage resulting from large, whole-body exposures. In contrast, the US Food and Drug Administration approves products for radiation dermatitis or “burns caused by radiation oncology procedures.” A review of the literature and comparison of clinical presentations shows that each of these terms represents a similar injury, and can be used interchangeably. Herein we provide a comparative review of the commonly used terminology for radiation-induced skin injury. Further, we recommend standardization across clinicians, providers, and researchers involved in the diagnosis, care, and investigation of radiation-induced skin injury. This will facilitate collaboration and broader inclusion criteria for grant-research and clinical trials and will assist in assessing therapeutic options particularly relevant to patient skin pigmentation response differences. more...

Wounds to the head, neck, and extremities have been estimated to account for ∼84% of reported combat injuries to military personnel. Volumetric muscle loss (VML), defined as skeletal muscle injuries in which tissue loss results in permanent functional impairment, is common among these injuries. The present standard of care entails the use of muscle flap transfers, which suffer from the need for additional surgery when using autografts or the risk of rejection when cadaveric grafts are used. Tissue engineering (TE) strategies for skeletal muscle repair have been investigated as a means to overcome current therapeutic limitations. In that regard, human hair-derived keratin (KN) biomaterials have been found to possess several favorable properties for use in TE applications and, as such, are a viable candidate for use in skeletal muscle repair. Herein, KN hydrogels with and without the addition of skeletal muscle progenitor cells (MPCs) and/or insulin-like growth factor 1 (IGF-1) and/or basic fibroblast growth factor (bFGF) were implanted in an established murine model of surgically induced VML injury to the latissimus dorsi (LD) muscle. Control treatments included surgery with no repair (NR) as well as implantation of bladder acellular matrix (BAM). In vitro muscle contraction force was evaluated at two months postsurgery through electrical stimulation of the explanted LD in an organ bath. Functional data indicated that implantation of KN+bFGF+IGF-1 (n = 8) enabled a greater recovery of contractile force than KN+bFGF (n = 8)***, KN+MPC (n = 8)**, KN+MPC+bFGF+IGF-1 (n = 8)**, BAM (n = 8)*, KN+IGF-1 (n = 8)*, KN+MPCs+bFGF (n = 9)*, or NR (n = 9)**, (*p more...

Tunable erosion of polymeric materials is an important aspect of tissue engineering for reasons that include cell infiltration, controlled release of therapeutic agents, and ultimately to tissue healing. In general, the biological response to proteinaceous polymeric hydrogels is favorable (e.g., minimal inflammatory response). However, unlike synthetic polymers, achieving tunable erosion with natural materials is a challenge. Keratins are a class of intermediate filament proteins that can be obtained from several sources, including human hair, and have gained increasing levels of use in tissue engineering applications. An important characteristic of keratin proteins is the presence of a large number of cysteine residues. Two classes of keratins with different chemical properties can be obtained by varying the extraction techniques: (1) keratose by oxidative extraction and (2) kerateine by reductive extraction. Cysteine residues of keratose are "capped" by sulfonic acid and are unable to form covalent cross-links upon hydration, whereas cysteine residues of kerateine remain as sulfhydryl groups and spontaneously form covalent disulfide cross-links. Here, we describe a straightforward approach to fabricate keratin hydrogels with tunable rates of erosion by mixing keratose and kerateine. SEM imaging and mechanical testing of freeze-dried materials showed similar pore diameters and compressive moduli, respectively, for each keratose-kerateine mixture formulation (∼1200 kPa for freeze-dried materials and ∼1.5 kPa for hydrogels). However, the elastic modulus (G') determined by rheology varied in proportion with the keratose-kerateine ratios, as did the rate of hydrogel erosion and the release rate of thiol from the hydrogels. The variation in keratose-kerateine ratios also led to tunable control over release rates of recombinant human insulin-like growth factor 1. more...

Driven by new discoveries in stem cell biology and regenerative medicine there is broad interest in biomaterials that go beyond basic interactions with cells and tissues to actively direct and sustain cellular behavior. Keratin biomaterials have the potential to achieve these goals but have been inadequately described in terms of composition structure and cell instructive characteristics. In this manuscript we describe and characterize a keratin based biomaterial demonstrate self assembly of cross linked hydrogels investigate a cell specific interaction that is dependent on the hydrogel structure and mediated by specific biomaterial receptor interactions and show one potential medical application that relies on receptor binding the ability to achieve hemostasis in a lethal liver injury model. Keratin biomaterials represent a significant advance in biotechnology as they combine the compatibility of natural materials with the chemical flexibility of synthetic materials. These characteristics allow for a system that can be formulated into several varieties of cell instructive biomaterials with potential uses in tissue engineering regenerative medicine drug and cell delivery and trauma. © 2012 Elsevier Ltd. more...

The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues, or organs to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues, and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate. © 2012 by Lippincott Williams and Wilkins. more...