Bovine Dermis Research Articles

Three-dimensional computation of fibre orientation, diameter and branching in segmented image stacks of fibrous networks.

Fibre topography of the extracellular matrix governs local mechanical properties and cellular behaviour including migration and gene expression. While quantifying properties of the fibrous network provides valuable data that could be used across a breadth of biomedical disciplines, most available techniques are limited to two dimensions and, therefore, do not fully capture the architecture of three-dimensional (3D) tissue. The currently available 3D techniques have limited accuracy and applicability and many are restricted to a specific imaging modality. To address this need, we developed a novel fibre analysis algorithm capable of determining fibre orientation, fibre diameter and fibre branching on a voxel-wise basis in image stacks with distinct fibre populations. The accuracy of the technique is demonstrated on computer-generated phantom image stacks spanning a range of features and complexities, as well as on two-photon microscopy image stacks of elastic fibres in bovine tendon and dermis. Additionally, we propose a measure of axial spherical variance which can be used to define the degree of fibre alignment in a distribution of 3D orientations. This method provides a useful tool to quantify orientation distributions and variance on image stacks with distinguishable fibres or fibre-like structures.

Fabrication of films with tailored properties by regulating the swelling of collagen fiber through pH adjustment

Acid swelling collagen fibers have been commonly used to prepare casing or film, but how the swelling degree regulates the properties of collagen fiber dispersions (CFD) and their related films are still unclear. Herein, variant swelling degrees of collagen fiber were obtained by controlling the pH of CFD. The swelling ratio of collagen fiber increased and then decreased with the decrease of pH from 4.0 to 1.5. The maximum viscosity, modulus and denaturation temperature appeared at pH 3, where the fibers interconnected to form a dense network structure. This sufficient swelling enabled excellent mechanical and thermodynamic properties of films, whereas insufficient swelling of CFD led to inferior properties. Films from collagen fiber swelled at pH 3 further showed a more ordered layer structure, but cross-sectional microstructures with disintegrated tiny fibers along with the reduction of triple helix content for those at low pH were observed. This study provided a better understanding and guidance of pH regulation in actual production of collagen films using bovine dermis.

Sub- and Supramolecular X-Ray Characterization of Engineered Tissues from Equine Tendon, Bovine Dermis, and Fish Skin Type-I Collagen.

Collagen represents one of the most widely used biomaterial for scaffolds fabrication in tissue engineering as it represents the mechanical support of natural tissues. It also provides physical scaffolding for cells and it influences their attachment, growth, and tissue regeneration. Among all fibrillary collagens, type I is considered one of the gold standard for scaffolds fabrication, thanks to its high biocompatibility, biodegradability, and hemostatic properties. It can be extracted by chemical and enzymatic protocols from several collagen-rich tissues, such as tendon and skin, of different animal species. Both the extraction processes and the manufacturing protocols for scaffolds fabrication provide structural and mechanical changes that can be tuned in order to deeply impact the properties of the final biomaterial. The aim of this review is to discuss the role of X-rays to study structural changes of type I collagen from fresh collagen-rich tissues (bovine, equine, fish) to the final scaffolds, with the aim to screen across available collagen sources and scaffolds fabrication protocols to be used in tissue regeneration.

Importance of extracellular matrix dynamics after surgical implantation of acellular scaffold.

Extracellular matrix dynamics mediates many important biological activities including tissue repairing process. Acellular scaffolds would be involved in the extracellular matrix dynamics of the host tissue after in vivo implantation. The remodeling process of acellular scaffold is also the reestablishment of extracellular matrix dynamics in acellular scaffold. In order to study the role of extracellular matrix dynamics on the remodeling process of acellular scaffold, acellular bovine pericardium (S1) and acellular bovine dermis (S2) were prepared. The in vitro characteristics and in vivo performance for dura defect repairing were tested. The results indicated that extracellular matrix dynamics played an important role after surgical implantation of the acellular scaffold. The extracellular matrix dynamics of the acellular scaffold restarted along with the infiltration of the host cells. The thoroughly degradation of S2 showed that an equilibrium extracellular matrix dynamics in the acellular scaffold should be established and successful integration between acellular scaffold and auto-dura could not guarantee tissue regeneration. In addition, there was a close relationship between the in vitro characteristics and the in vivo performance of the acellular scaffold. The in vitro characteristics had big influence on the restoration of extracellular matrix dynamics. Acellular scaffold could actively take part in the extracellular matrix dynamics and remodeling itself subsequently. Therefore, acellular scaffold showed great advantages to other scaffold materials for tissue regeneration.

Principles and development of collagen-mediated tissue fusion induced by laser irradiation

The mechanism underlying tissue fusion mediated by laser irradiation remains unclear. We clarify the mechanisms underlying laser-mediated tissue fusion using a novel model. Microscopic examinations of morphological changes within the adventitia of a bovine carotid artery and a collagen sheet prepared from bovine dermis showed collagen fibril bundle loosening and collagen fibre swelling following heating at 46 °C. An incised bovine carotid artery covered with a collagen sheet to which pressure and laser heat of 40 °C–52 °C were applied created a structure that was pressure resistant to >300 mmHg. Microscopic analyses of the irradiation site showed collagen fibril interdigitation. Hence, low-temperature laser-mediated tissue fusion causes collagen fibril bundles to loosen and swell, and crimping causes the fibres to intertwine. As the temperature declines, the loosened and swollen fibrils and fibres tighten, and collagen fibre interdigitation is completed. This technology could be applied to fuse tissues during surgery.

In vitro cytotoxicity, antioxidant and anti-inflammatory activities of Pittosporum viridiflorum Sims and Hypoxis colchicifolia Baker used traditionally against cancer in Eastern Cape, South Africa

Cancer is one of the leading causes of death both in developed and developing countries and was responsible for the loss of 9.6 million lives in 2018 alone. Development of drug resistant strains of cancer has hampered cancer therapy. Worldwide, plants have been reported to play a major role in the traditional treatment of cancer. Irinotecan, paclitaxel, and vincristine are some of the examples of plant derived compounds that are used as anticancer agents. This study evaluated the cytotoxicity, anti-inflammatory, and antioxidant activities of Pittosporum viridiflorum Sims and Hypoxis colchicifolia Baker, two plants used in South African traditional medicine for treating cancer. Acetone, ethanol, and water (hot and cold) extracts were screened against four human cancer lines (breast MCF-7, colorectal Caco-2, lung A549 and cervical Hela) for anticancer potential. Two normal cells; Vero monkey kidney and bovine dermis were used to test for cytotoxicity, and Salmonella typhimurium TA98 and TA100 were used to determine genotoxicity of the samples. The acetone extract of P. viridiflorum had significant cytotoxicity against the cancer cells (MCF7, Caco-2, A549 and Hela) with LC50 values ranging from 3.16–26.87 μg/ml. The same extract had noteworthy anti-inflammatory activity against 15-lipoxygenase with IC50 value = 5.01 μg/ml and was not toxic against Vero and bovine dermis cells nor was it genotoxic. This warrants further extensive study to determine the mechanism of action of anticancer and anti-inflammatory activities as well as to identify specific compounds responsible for the observed activities.

Antifungal, anti-oxidant activity and cytotoxicity of South African medicinal plants against mycotoxigenic fungi

Fungal strains belonging to genus Fusarium and Aspergillus are known to infect crops, resulting in threatened food security and less agricultural crop yields. The aim of the current work was to investigate the anti-mycotoxigenic activity, cytotoxic effect and antioxidant potential of selected South African medicinal plants extracts. The aqueous and organic extracts of the leaves from selected medicinal plants were investigated for their antifungal activity against various fungal strains that are known to infect crops and produce mycotoxins. Antioxidant activity, total phenolic and total flavonoids contents were also evaluated. Organic extract of Milletia grandis (E. Mey) Skeels revealed the lowest minimum inhibitory concentration (MIC) value of 0.01 mg/mL against Aspergillus ochraceous, Fusarium graminearum and Furasium oxysporum. Generally, organic extracts revealed significant antifungal activity compared to aqueous extracts. Carpobrutus eludis L. and Warburgia salutaris (G. Bertol) Chiov. revealed a potent cytotoxic effect yielding 50 % lethal concentration (LC50) value of 0.01 mg/mL against Bovine dermis and Vero cells respectively. Ricinus communis L. revealed a 50 % inhibitory concentration (IC50) value of 945 μg/mL against 2, 2 diphenyl-picryl-hydrazyl (DPPH). Generally, the plant species revealed lower flavonoids compared to phenolic contents. The biological activity of the selected plant extracts may be attributed to the high phenolic contents.

Fetal bovine dermis as an alternative to allograft in large burn injuries

IntroductionDermal substitutes can be an essential treatment option for patients with very large burn injuries. We reviewed and compared our experience with a fetal bovine dermis dermal substitute versus allograft for adult burn patients with large burn injuries. MethodsAfter obtaining regulatory approval from our local institutional review board, we performed a 1 year retrospective review of adult burn patients with a TBSA of 50% or greater who underwent grafting with either fetal bovine dermis or allograft. We collected data that included age, TBSA, length of stay, number of operations,% area grafted with either allograft or fetal bovine dermis, and time between allograft or fetal bovine dermis grafting to autografting. All mean values are mean ± standard deviation, and all median values are median (interquartile range) ResultsOverall for this review 15 patients met entry criteria. The mean age was 36 ± 9 years and mean TBSA was 71 ± 15%. Mean area grafted with either allograft (ALLO) or fetal bovine dermis (FBD) was 20 ± 8%. Mean time from grafting with ALLO or FB was 30 ± 12 days. There was no difference in median age between the ALLO group (30 (26–31)) and FBD group (35 (32–46) and there was no difference in median TBSA between the ALLO group (68(60–75)%) and FBD group (69(59–88)%). The median area grafted with allograft was 20(20–30)% which was not significantly different than the median area grafted with FBD (16.5(11–26)%). Additionally, there was no difference between the time from grafting with ALLO to autologous skin grafting (26(22–36) days) and the time from grafting with FBD to autologous skin grafting (25.5(21–32) days). ConclusionsFetal bovine dermis is an acceptable alternative to allograft in patients with a large TBSA burn-injury. Further studies are needed to determine if infectious and functional outcomes are improved with fetal bovine dermis.

Scientific rationale for traditional use of plants to treat tuberculosis in the eastern region of the OR Tambo district, South Africa

Ethnopharmacological relevanceTuberculosis (TB) remains a major health problem for humans worldwide, and was responsible for 1.4 million human deaths in 2015 alone. Although there is treatment for TB, emerging multi-drug, extensively drug and totally drug resistant forms of this disease, as well as co-infection with human immunodefiency virus (HIV) continue to worsen the situation. South Africa is among countries with reported traditional use and published documentation of such knowledge concerning the use of plants against TB. Based on a previous study where plants used traditionally for treating TB in the eastern region of OR Tambo district, South Africa, were documented, the present study aimed to determine the antimycobacterial effect, cytotoxicity and genotoxicity of plants selected from that list. Material and methodsAcetone, 70% ethanol, cold and hot water extracts were tested for antimycobacterial activity against saprophytic Mycobacterium species including M. aurum, M. bovis BCG, M. gordonae, M. fortuitum, and M. smegmatis using a microdilution method. Extracts with MIC values less than 1 mg/ml against at least three Mycobacterium strains were evaluated for antimycobacterial activity against pathogenic Mycobacterium strains including M. tuberculosis H37RV, M. tuberculosis and M. bovis, cytotoxicity (against Vero monkey kidney and bovine dermis cells), and genotoxicity (against Salmonella typhimurium TA98 and TA100). ResultsThe MIC values of the extracts ranged from 0.02 to 2.50 mg/ml, LC50 values of twenty-nine extracts ranged from 0.001 to > 1 mg/ml and the highest selectivity index was 79.50, an extremely promising value. Phymaspermum acerosum roots and leaves (ethanol and water) extracts had the best MIC value (0.02 mg/ml) against at least one Mycobacterium strain. It was interesting to note the lack of cytotoxicity of these extracts with the highest selectivity index value of 39.75. Pterocelastrus echinatus bark acetone and Protorhus longifolia leaf hot water extracts were the most cytotoxic with LC50 = 0.001 and 0.008 mg/ml, respectively, whereas Pittosporum viridiflorum bark water extract was genotoxic. Among non-pathogenic strains, M. gordonae, M. aurum, M. smegmatis showed good correlation of activity with pathogenic M. tuberculosis H37Rv, M. tuberculosis and M. bovis, however, M. aurum was the best predictor with Mycobacterium tuberculosis H37Rv (correlation coefficient value = 0.73). ConclusionThe results indicate that Heteromorpha trifoliata and Phymaspermum acerosum should be investigated further for antimycobacterial efficacy against drug resistant strains of Mycobacterium.

Bioprosthetic Versus Synthetic Mesh: Analysis of Tissue Adherence and Revascularization in an Experimental Animal Model.

Both synthetic and bioprosthetic meshes play important roles in surgical procedures such as ventral hernia repair. Although sometimes used interchangeably, these devices have inherently different properties. We therefore sought to better understand how these materials interact with the host environment to optimize surgical techniques and to improve outcomes. Synthetic mesh (polypropylene, Prolene) or bioprosthetic mesh (acellular fetal/neonatal bovine dermis, SurgiMend) was implanted intraperitoneally into rats lateral to a ventral incision in a novel intra-abdominal implant model. Two variables were modified with each material: (1) tight or loose tissue apposition, altered by modifying suture placement; and (2) abdominal wall injury, altered by selective abrasion of the peritoneal lining. After 5 weeks, the meshes and abdominal wall were evaluated grossly and histologically. The analysis focused on the degree of inflammatory response, neovascularization, and mesh adherence to the surrounding tissues. Synthetic mesh adhered to the abdominal wall and visceral organs, regardless of the degree of apposition or tissue injury, due to a foreign body-mediated inflammatory reaction. In areas of noninjured peritoneal lining, SurgiMend was adherent peri-suture. Neovascularization entered the mesh from these apposition points and spread outward. In areas of denuded peritoneal lining, the adherent and vascularized areas were significantly greater and not merely coincident with suture placement. The inflammatory and wound healing responses with bioprosthetic mesh seem fundamentally different from synthetic mesh. Understanding these differences may lead to varied outcomes in adherence and vascularization of the materials, and ultimately the efficacy of hernia repair. Additionally, these differences highlight the need for further basic research to optimize mesh selection for surgical technique.

516 Fetal Bovine Dermis as an Alternative to Allograft for Large Burn Injuries

516 Fetal Bovine Dermis as an Alternative to Allograft for Large Burn Injuries

Investigation of apoptosis in cultured cells infected with equine herpesvirus 1

Many viruses alter different stages of apoptosis of infected cells as a strategy for successful infection. Few studies have addressed mechanisms of equine herpesvirus 1 (EHV-1) strain-induced cell death. We investigated the effect of an abortigenic strain (AR8 strain) on heterologous Madin–Darby bovine kidney cells and homologous equine dermis (ED) cells cell lines. We compared morphologic and biochemical features of early and late apoptosis at different postinfection times. We investigated translocation of phosphatidylserine to the cell surface, nuclear fragmentation and changes in the cytoskeleton using flow cytometry and annexin V/propidium iodide staining, DNA laddering, terminal deoxynucleotidyl transferase UTP nick-end labeling assay and immunofluorescence staining of cytokeratin 18 cleavage. AR8 EVH-1 strain interfered with apoptosis in both cell lines, particularly during the middle stage of the replication cycle; this was more evident in ED cells. Although this antiapoptotic effect has been reported for other alpha herpesviruses, our findings may help elucidate how EHV-1 improves its infectivity during its cycle.

Reconstruction of Anterior Tracheal Defects Using a Bioengineered Graft in a Porcine Model

Reconstruction of long-segment tracheal defects can be challenging and a suitable tracheal substitute remains lacking. We sought to create a bioengineered tracheal graft to repair such lesions using acellullar bovine dermis extracellular matrix (ECM) and male human mesenchymal stem cells (hMSCs) and implant it in a porcine model. hMSCs were seeded on the ECM and incubated for 1 week with chondrogenic factors. An anterior 4cm× 3 cm defect was surgically created in the trachea of 4-week-old female Yorkshire pigs. The defect was reconstructed using the bioengineered graft (n= 7) or control (n= 3, ECM only). The study duration was 3 months. Survival ranged from 7 days (n= 3) to 3months (n= 7). Early death was due to graft malacia (n=1, control), graft infection (n= 1, bioengineered), and pneumonia (n= 1, bioengineered). There was substantial animal growth at 3 months (>200% weight). Surveillance bronchoscopy showed patent airway, mild stenosis, and integration of the graft with the native trachea. On histology, luminal epithelialization and neovascularization with scant submucosa were observed in both the bioengineered graft and control groups. Chondrogenesis was seen only in the bioengineered graft. The neocartilage was less mature and organized compared to native cartilage. SRY immunostain was positive in the neocartilage but not control or native trachea. We demonstrate the feasibility of the bioengineered graft for reconstruction of long anterior tracheal defects with favorable short-term outcomes. Furthermore, we show its ability to facilitate chondrogenesis, neovascularization, and epithelialization. Importantly, it supported rapid animal growth offering potential solutions for both pediatric and adult applications.

Exposure of bovine dermal tissue to ultraviolet light under the Antarctic ozone hole

Bovine dermis was exposed outdoors in the Antarctic in 2013 to study the skin damage caused by short-wavelength ultraviolet light under the ozone hole. Collagen was extracted from the exposed dermis with pepsin. The amount of solubilized collagen in the exposed dermis was only 20%–40% of that in dermis shielded from ultraviolet light. The dermis was most difficult to extract when exposed in summer, and then when exposed in spring. Differential scanning calorimetry was used to determine the melting endothermic behavior of the dermal tissue. The peak temperature was highest for the dermis exposed in summer. The exposed dermis was degraded with cyanogen bromide to determine whether cross-linking had occurred. Cross-linked peptides were detected in the dermis exposed in summer or spring, but the dermis exposed in autumn did not differ markedly from the light-shielded dermis. These data show that cross-linkages were readily formed in the collagen molecule chains in dermis exposed to ultraviolet light in summer, when solar elevation is highest and the period of sunshine is longest. A comparison of the dermis exposed in spring and that exposed in autumn showed that cross-linkages were formed more readily by ultraviolet light in spring, when the ozone hole occurred.

Peyronie's disease: The results of surgical treatment with dermal or bovine dermis corporografting (15 years experience)

Peyronie's disease: The results of surgical treatment with dermal or bovine dermis corporografting (15 years experience)

Influence of collagen source on fibrillar architecture and properties of vitrified collagen membranes.

Collagen vitrigel membranes are transparent biomaterials characterized by a densely organized, fibrillar nanostructure that show promise in the treatment of corneal injury and disease. In this study, the influence of different type I collagen sources and processing techniques, including acid-solubilized collagen from bovine dermis (Bov), pepsin-solubilized collagen from human fibroblast cell culture (HuCC), and ficin-solubilized collagen from recombinant human collagen expressed in tobacco leaves (rH), on the properties of the vitrigel membranes was evaluated. Postvitrification carbodiimide crosslinking (CX) was also carried out on the vitrigels from each collagen source, forming crosslinked counterparts BovXL, HuCCXL, and rHXL, respectively. Collagen membrane ultrastructure and biomaterial properties were found to rely heavily on both collagen source and crosslinking. Bov and HuCC samples showed a random fibrillar organization of collagen, whereas rH vitrigels showed remarkable regional fibril alignment. After CX, light transmission was enhanced in all groups. Denaturation temperatures after CX increased in all membranes, of which the highest increase was seen in rH (14.71°C), suggesting improved thermal stability of the collagen fibrils in the membranes. Noncrosslinked rH vitrigels may be reinforced through CX to reach levels of mechanical strength and thermal stability comparable to Bov.

Morphology of collagen matrices for tissue engineering (biocompatibility, biodegradation, tissue response)

to perform a comparative morphological study of biocompatibility, biodegradation, and tissue response to implantation of collagen matrices (scaffolds) for tissue engineering in urology and other areas of medicine. Nine matrix types, such as porous materials reconstructed from collagen solution; a collagen sponge-vicryl mesh composite; decellularized and freeze-dried bovine, equine, and fish dermis; small intestinal submucosa, decellularized bovine dura mater; and decellularized human femoral artery, were implanted subcutaneously in 225 rats. The tissues at the implantation site were investigated for a period of 5 to 90 days. Classical histology and nonlinear optical microscopy (NLOM) were applied. The investigations showed no rejection of all the collagen materials. The period of matrix bioresorption varied from 10 days for collagen sponges to 2 months for decellularized and freeze-dried vessels and vicryl meshes. Collagen was prone to macrophage resorption and enzymatic lysis, being replaced by granulation tissue and then fibrous tissue, followed by its involution. NLOM allowed the investigators to study the number, density, interposition, and spatial organization of collagen structures in the matrices and adjacent tissues, and their change over time during implantation. The performed investigation could recommend three matrices: hybrid collagen/vicryl composite; decellularized bovine dermis; and decellularized porcine small intestinal submucosa, which are most adequate for tissue engineering in urology. These and other collagen matrices may be used in different areas of regenerative medicine.

In vitro cytotoxicity and genotoxicity of five Ochna species (Ochnaceae) with excellent antibacterial activity

Extracts and fractions of some Ochna species had excellent antibacterial activity. Before considering the potential therapeutic use of these extracts it is important to determine the safety of extracts. The cytotoxicity of Ochna natalitia, Ochna pretoriensis, Ochna pulchra, Ochna gamostigmata, and Ochna serrulata (Ochnaceae) was determined in monkey kidney (Vero) cells, human hepatocellular carcinoma (C3A) cells and bovine dermis cells using the mitochondrial viability MTT assay. Their potential mutagenic effects were also determined using the Ames test with strains Salmonella typhimurium TA98 and TA100 with and without metabolic activation. The LC50 values (the lethal concentration at which 50% of the cells are killed) of the extracts on the various cell lines ranged from 26 to 99μg/ml. None of the plant species was mutagenic (mutagenic index values≤1.59 for TA98 and ≤0.92 for TA100). In a previous study, we determined the antibacterial activity of the five extracts against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa. From this we calculated the selectivity index (SI) values by dividing the LC50 value by the minimum inhibitory concentration (MIC) to obtain the ratio of toxicity to bioactivity of each extract. The plant extracts had low SI values≤1.307. This is a clear indication of non-selective toxicity, i.e. extracts are almost equally toxic to the bacteria and mammalian cell lines used in the assays. As a result, the extracts may have limited application as ingestible or intravenous therapeutic agents based on the in vitro findings. However, it may be necessary to also evaluate in vivo toxicity of the extracts in animal models as in vitro toxicity does not always equate to in vivo toxicity because of the difference in physiological microenvironment in live animals and tissue culture. Additionally, if it is the case that the toxic compounds are not the same as the active compounds, it may be possible to potentiate the extracts by the removal of toxic compounds and concentration of active compounds. The extracts may then be useful for development into treatments for topical bacterial infections.

Histologic Analysis of Fetal Bovine Derived Acellular Dermal Matrix in Tissue Expander Breast Reconstruction

This study seeks to determine human host response to fetal bovine acellular dermal matrix (ADM) in staged implant-based breast reconstruction. A prospective study was performed for patients undergoing immediate breast reconstruction with tissue expander placement and SurgiMend acellular fetal bovine dermis. At the time of exchange for permanent implant, we obtained tissue specimens of SurgiMend and native capsule. Histological and immunohistochemical assays were performed to characterize the extent of ADM incorporation/degradation, host cell infiltration, neovascularization, inflammation, and host replacement of acellular fetal bovine collagen. Seventeen capsules from 12 patients were included in our study. The average "implantation" time of SurgiMend was 7.8 months (range, 2-23 months). Histological analysis of the biopsy of tissue revealed rare infiltration of host inflammatory cells, even at 23 months. One patient had an infection requiring removal of the tissue expander at 2 months. Contracture, inflammatory changes, edema, and polymorphonuclear leukocyte infiltration were rare in the ADM. An acellular capsule was seen in many cases, at the interface of SurgiMend with the tissue expander. SurgiMend demonstrated a very infrequent inflammatory response. An antibody specific to bovine collagen allowed for direct identification of bovine collagen separate from human collagen. Cellular infiltration and neovascularization of SurgiMend correlated with the quality of the mastectomy skin flap rather than the duration of implantation. Future studies are needed to further characterize the molecular mechanisms underlying tissue incorporation of this product.

Cellular Response to a Novel Fetal Acellular Collagen Matrix: Implications for Tissue Regeneration

Introduction. PriMatrix (TEI Biosciences Inc., Boston, MA, USA) is a novel acellular collagen matrix derived from fetal bovine dermis that is designed for use in partial- and full-thickness wounds. This study analyzes the cellular response to PriMatrix in vivo, as well as the ability of this matrix to facilitate normal tissue regeneration. Methods. Five by five mm squares of rehydrated PriMatrix were implanted in a subcutaneous fashion on the dorsum of wild-type mice. Implant site tissue was harvested for histology, immunohistochemistry (IHC), and flow cytometric analyses at multiple time points until day 28. Results. PriMatrix implants were found to go through a biological progression initiated by a transient infiltrate of inflammatory cells, followed by mesenchymal cell recruitment and vascular development. IHC analysis revealed that the majority of the implanted fetal dermal collagen fibers persisted through day 28 but underwent remodeling and cellular repopulation to form tissue with a density and morphology consistent with healthy dermis. Conclusions. PriMatrix implants undergo progressive in vivo remodeling, facilitating the regeneration of histologically normal tissue through a mild inflammatory and progenitor cell response. Regeneration of normal tissue is especially important in a wound environment, and these findings warrant further investigation of PriMatrix in this setting.