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The importance of multimodality in the diagnosis and treatment of medical conditions cannot be overemphasized. Herewith a case of facial malignancy encompassing all stages of management and requiring multimodal approaches for diagnosis, oncological treatment, anatomical reconstruction, and ultimately aesthetics and "identity" is presented., Competing Interests: Marek Dobke and Frederic J. Kolb report no competing interests to declare. Douglas M. Arm is an employee of MicroVascular Tissues, Inc., which provided the mVASC graft used in this case., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: Publications aimed at improving the quality of evidence in wound care clinical research have stressed the importance of minimizing study bias. In particular, lack of a universal definition of healing in wound studies leads to detection bias, resulting in noncomparable healing rates., Objective: This report analyzes the steps taken to reduce the main sources of bias in a particular RCT (the HIFLO Trial) that evaluated healing in DFUs using microvascular tissue., Materials and Methods: To address "definition of healing"-induced detection bias, 3 blinded adjudicators independently assessed each DFU using a rigorous 4-part definition of healing. Adjudicator responses were analyzed to assess reproducibility. Predefined criteria were also included to avoid bias owing to selection, performance, attrition, and reporting., Results: Rigor and comparability across sites were ensured through investigator training, consistent SOC, data monitoring, and independent statistical and ITT-only analysis. The level of agreement among adjudicators was greater than or equal to 90% for each of the 4-part healing criteria., Conclusions: High-level agreement by blinded adjudicators confirmed that DFUs in the HIFLO Trial were consistently assessed for healing without bias, validating the most rigorous assessment criteria to date. The findings reported herein may prove beneficial for others seeking to minimize bias in wound studies.

Aims: Profiling of microvascular tissue allows identification of components that stimulate wound healing. Here we study those elements for biological effect and establish clinical proof-of-concept using a microvascular tissue graft (mVASC ® ) in chronic refractory wounds. Methods: mVASC was characterized for tissue fragments and protein composition, evaluated for angiogenic potential in preclinical models, and applied clinically to a series of nonhealing wounds with compromised vascularity of different etiologies. Results: mVASC increased endothelial cell migration in vitro and angiogenesis in mouse ingrowth and hindlimb ischemia models. Clinically, mVASC stimulated wound neovascularization, granulation and epithelialization, and complete and durable healing. Conclusion: Microvascular tissue contains elements relevant to tissue repair and can be clinically applied to enable or accelerate the closure of challenging wounds.

Background: Processed microvascular tissue (PMVT), a human structural allograft, is derived from lyophilized human tissue containing microcirculatory cellular components. Since PMVT serves as a source of extracellular matrix (ECM), growth factors, cytokines, and chemokines modulating angiogenesis, inflammation, apoptosis, and endogenous cell recruitment, we hypothesized its application would accelerate wound regeneration in a validated pressure ulcer (PU) model developed in C57BL/6 mice using two 24-hour cycles of skin ischemia/reperfusion created by placement and removal of external magnets., Methods: Two identical PU injuries (n = 50 female mice) were treated with (a) topical particulate PMVT, (b) injected rehydrated PMVT, or (c) saline control injection, and assessed daily for closure rates, scab formation/removal, and temperature. A baseline control cohort (n = 5) was euthanized at day 0 and treatment group cohorts (n = 5) were killed at 3, 7, or 14 days postinjury. The PU injuries were collagenase-digested for flow cytometric analysis of inflammatory, reparative, and stem cell frequencies and analyzed by hematoxylin and eosin (H&E) histology and immunofluorescence., Results: PMVT-accelerated wound closure, most notably, topical PMVT significantly increased mean closure from d5 (13% versus -9%) through d13 (92% versus 38%) compared with phosphate-buffered saline (PBS) controls ( P < 0.05). PMVT also hastened scab formation/removal, significantly accelerated disappearance of inflammatory myeloid (CD11b+) cells while upregulating α-smooth muscle actin, vascular endothelial growth factor A, and placental growth factor and raised skin temperature surrounding the PU site, consistent with increased blood flow., Conclusions: These results indicate that PMVT has potential as an advanced treatment for restoring normal tissue function in ischemic wounds and merits clinical study.

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution ® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing.

Background: Successful long-term volume retention of an autologous fat graft is problematic. The presence of contaminating cells, tumescent fluid, and free lipid in the graft contributes to disparate outcomes. Better preparation methods for the fat graft before transplantation may significantly improve results., Methods: Subcutaneous fat from 22 donors was divided and processed using various graft preparation methods: (1) no manipulation control, (2) gravity separation, (3) Coleman centrifugation, and (4) simultaneous washing with filtration using a commercially available system (Puregraft; Cytori Therapeutics, Inc., San Diego, Calif.). Fat grafts from various preparation methods were examined for free lipid, aqueous liquid, viable tissue, and blood cell content. Adipose tissue viability was determined by measuring glycerol release after agonist induction of lipolysis., Results: All test graft preparation methods exhibited significantly less aqueous fluid and blood cell content compared with the control. Grafts prepared by washing with filtration exhibited significantly reduced blood cell and free lipid content, with significantly greater adipose tissue viability than other methods., Conclusion: Washing with filtration within a closed system produces a fat graft with higher tissue viability and lower presence of contaminants compared with grafts prepared by alternate methods.

Platelets contain growth factors that are believed to stimulate early fracture repair. Autologous platelets can be sequestered, concentrated, and mixed with thrombin to yield a so-called autologous growth factor gel, which might enhance bone repair or bone graft incorporation. The effect of this platelet concentrate on total tissue and bone ingrowth into porous coralline hydroxyapatite was studied in a bone chamber rat model. Chambers with the platelet concentrate showed a significant increase in bone and total tissue ingrowth distance compared to untreated controls, indicating a platelet concentrate might enhance the clinical performance of porous hydroxyapatite in bone replacement.

The stromal elements of human bone marrow include cells, referred to as mesenchymal stem cells (MSCs), that have the potential to differentiate into bone, cartilage, fat, and hematopoietic-supportive stromal tissue. MSCs have been isolated and maintained in culture, and in vivo and in vitro assays have been used to show that these cultured cells possess osteochondral potential. Human mesenchymal stem cells (hMSCs) were combined in a range of proportions with human dermal fibroblasts (hDFs), shown to be devoid of osteochondral potential, and tested in these assays. Results suggest that hMSCs may be intentionally "contaminated" with 25-50% hDFs and still elicit a positive response in alkaline phosphatase and calcium in vitro osteogenic assays, form cartilage in pellet culture conditions, and produce bone when loaded into porous hydroxyapatite-tricalcium phosphate ceramic cubes and then implanted subcutaneously into immunocompromised mice. Although hMSCs can be purified and culture-expanded as a homogeneous subset of marrow cells, the dilution results reported here are encouraging for the prospective use of these cells in clinical applications, where repair grafts that contain 100% hMSCs almost surely will become infiltrated with host connective tissue and vasculature, which will dilute the initial concentration of hMSCs., (Copyright 2000 Wiley-Liss, Inc.)

The availability of osteogenic proteins for orthopedic applications has led to great interest in developing delivery systems for these substances. Standard release rate models are applicable in most biological settings, but orthopedic implants usually bear mechanical loads. To determine whether a release rate model for load bearing applications must consider mechanical stress, the effects of dynamic mechanical stress on the in vitro release kinetics of two model proteins, bovine albumin (BA) and trypsin inhibitor (TI), from a biodegradable film were evaluated. Biodegradable poly(lacticco-glycolic acid) cylindrical implants with embedded proteins were subjected to cyclic three point bending loading of 720 cycles/day at 0.4 Hz for 2 weeks. Protein release into solution, swelling and mass loss changes, molecular weight degradation, and the presence of microstructural stress cracks and pores in the polymer carrier were evaluated. Cumulative BA and TI releases with time were significantly higher when a cyclic bending load was applied and increased with the magnitude of the load. Mass loss was not significantly greater, nor was swelling or molecular weight change of the polymer carrier in this 2-week interval. Pores on the surface of the polymer in the highest stress region were elongated into cracks, compared with pores in the low-stress region of the same implant, which were roughly circular. This implies that the pores probably act as stress risers to initiate cracks, which then expose more surface area, increasing protein release.

Platelet-derived growth factor (PDGF) is one of several osteogenic factors which affect bone growth and fracture healing. This study examined the potential of hydroxyapatite (HA) rods with interconnected pores of mean diameter 200 microns to be used as a matrix for the release of PDGF to enhance bone ingrowth into the implant. In the initial phase of the study the sustained release of PDGF from the HA rods was characterized in vitro for two different PDGF loadings, 10 and 100 micrograms per implant. The second phase of the study examined bone ingrowth in HA implants placed into the medullary canals of rabbit femora. The specimens were dumb-bell shaped, with a reduced central diameter so that bone growth across a gap could also be determined. Bone ingrowth into HA implants was compared with growth into HA implants loaded with 100 micrograms of PDGF. Pushout measurements were made of average shear strength across the bone-implant interface and backscatter scanning electron microscopy of thick sections was used to quantify the amount of bone ingrowth into the implant. Although greater interfacial shear strength and area of ingrowth were observed, especially across gap sites, in specimens loaded with PDGF, no difference was statistically significant.

Chronic osteomyelitis is one of the most serious complications of orthopedic open fracture treatment. The objective of this study was to develop a biodegradable implant coating with impregnated antibiotics as an adjunct to current therapy. We used a polylactic-co-glycolic acid copolymer (PLGA) as the biodegradable carrier and gentamicin as the antibiotic. Our objectives were to establish elution characteristics of the antibiotic from the polymer, and determine if the coated orthopedic implants would inhibit bacterial growth in vitro. In the elution study, coated implants were incubated in phosphate buffered saline (PBS) at 37 degrees C and sampled daily for gentamicin levels. The in vitro model consisted of test tubes containing Mueller-Hinton culture broth inoculated with 5 x 10(6) cfu of Staphylococcus aureus and incubated at 37 degrees C. The implants were switched to a new set of inoculated tubes each day. Tubes were sampled for colony counting to determine bactericidal effects. Implant coatings consisted of 40 mg of gentamicin as a 20% mixture with PLGA. The elution curve showed an average level of 138 micrograms/mL over 15 days. This local concentration would be more than adequate to kill susceptible organisms. The in vitro study showed a significant reduction in bacterial growth in the test tubes containing coated implants. Control tubes averaged 2.5 x 10(8) cfu/mL of S.aureus over 24 days. Coated implant tubes averaged 0.9 cfu/mL. This was a reduction of greater than 99.999% (p < 0.0001). This study showed that a thin biodegradable implant coating can be developed with bactericidal activity against the organisms frequently associated with osteomyelitis in cases of open fractures.

A series of polymers, bisphenol A-based poly(phosphoesters), were evaluated as degradable biomaterials. Degradation was observed for the four polymers studied under both in vitro and in vivo conditions. The rate of degradation was affected by polymer side-chain structure and correlated with the swelling behavior. The ethyl side-chain polymers absorbed more water than their phenyl counterparts. Among the sterilization methods, UV irradiation followed by antibiotic treatment was the most suitable, as steam autoclave and ethylene oxide treatments altered the properties of several of the poly (phosphoesters). Tissue response to the poly(phosphoesters) in rabbits was characterized by minor encapsulation and slight or no lymphocyte, giant cell, or macrophage activity. No evidence of edema or necrosis was found. The elastic moduli of these materials varied from 488 MPa for poly(bisphenol A-ethylphosphate) (BPA/EOP) to 627 MPa for the more rigid poly(bisphenol A-phenylphosphonate) (BPA/PP). The ultimate strength, modulus, and energy to failure of BPA/PP were lower than those of similarly compression molded high-molecular-weight poly(L-lactic acid) (PLLA).